促红细胞生成素联合基质细胞衍生因子-1在内皮祖细胞促血管新生中作用的研究
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摘要
第一部分内皮祖细胞的分离培养和鉴定
目的:利用实验室已建立的外周血内皮祖细胞(endothelial progenitor cells,EPCs)分离培养方案,建立EPCs的培养体系并进行细胞表型和功能的检测与鉴定,为后续的实验研究提供细胞来源。
方法:采集新西兰大白兔静脉外周血20ml,以密度梯度离心法获得单个核细胞,将细胞放入涂有0.1%纤连蛋白的培养皿中,在加有20%胎牛血清(FBS)和EGM-2 SingleQuots的内皮细胞基础培养基-2(EBM-2)中培养。于培养第7d应用免疫荧光检测细胞标志CD133,CD34,vWF,CD45抗原的表达;利用DiI-acLDL和FITC-UEA-1吸收试验鉴定内皮功能。
结果:单个核细胞在内皮条件下培养,48h后逐渐贴壁,第3d细胞呈梭形或不规则形,并逐渐变大,第7d梭形细胞增多,部分视野观察到梭形细胞首尾相连形成条索样结构。荧光显微镜观察CD133,CD34,vWF阳性率分别为83.11±3.46%,82.87±4.66%,77.45±6.71%,CD45阴性。并且,有＞90%的细胞吸收DiI-ac LDL和FITC-UEA-1。
结论:应用本研究方法从外周血途径分离、培养和扩增获得EPC,具有内皮祖细胞的特征和功能。
第二部分基质细胞衍生因子-1对内皮祖细胞的体外作用
目的:制备本实验室已冻存的病毒基因载体转导细胞NIH3T3/SDF-1和NIH3T3/LacZ细胞并检测细胞功能,利用其分泌基质细胞衍生因子-1(SDF-1)的特点研究对体外培养、扩增的EPC的影响。
方法:解冻NIH3T3细胞通过逆转录病毒转导SDF-1α基因和LacZ基因后制作能表达SDF-1的NIH3T3细胞(NIH3T3/SDF-1)和表达LacZ的NIH3T3/LacZ细胞。用ELASA法测定NIH3T3细胞,NIH3T3/SDF-1细胞在体外SDF-1表达情况,及存在EPO(10IU/ml)是对细胞表达SDF-1的影响,β-Gal染色法鉴定NIH3T3/LacZ细胞。用改良Boyden小室法检测NIH3T3/SDF-1细胞表达的SDF-1对内皮祖细胞EPCs体外迁移作用,DAPI染色法检测SDF-1对EPCs凋亡影响。
结果:冻存细胞可顺利解冻,培养细胞存活细胞率≥90%。转导入SDF-1表达载体的NIH 3T3/SDF-1细胞24小时可产生147±6 ng SDF-1/10~6细胞,转导入LacZ表达载体的NIH3T3/LacZ细胞可表达LacZ,细胞β-Gal染色阳性,为蓝色。EPO的存在并不能直接影响NIH3T3和NIH3T3/SDF-1细胞中SDF-1的表达。当EPCs与NIH3T3/SDF-1细胞共培养时同单独NIH3T3细胞共培养时相比迁移较多,(分别为31±9和13±4迁移细胞,P＜0.05)。并且,当在L-NMMA存在时,EPCs和NIH 3T3/SDF-1细胞共培养后迁移细胞明显减少为16±4(P＜0.05)。而与NIH 3T3/SDF-1细胞共培养的EPCs中凋亡发生率与同NIH 3T3细胞共培养的EPCs中凋亡发生率相比较低(分别为17±4%,30±7%P＜0.05)。L-NMMA的存在并不明显影响与NIH 3T3/SDF-1细胞共培养的EPCs中凋亡发生率(18±5%P＞0.05)。
结论:体外迁移实验表明EPC可在NIH3T3/SDF-1细胞分泌SDF-1的趋化作用下迁移,SDF-1可抑制EPCs凋亡。SDF-1迁移效应是通过一氧化氮(NO)途径,但NO没有参加SDF-1抑制EPC凋亡的过程。EPO并不影响NIH3T3/SDF-1细胞SDF-1的表达。本研究为下一步研究SDF-1在体内趋化EPC以及促血管新生的研究打下了必要的基础。
第三部分促红细胞生成素联合基质细胞衍生因子对小鼠缺血下肢血管新生的作用
目的:促红细胞生成素(EPO)可促进骨髓单核细胞动员到外周血中,基质细胞衍生因子1(SDF-1)可促进从骨髓动员后的祖细胞的在缺血组织中的归巢和血管新生。我们假设联合应用EPO和SDF-1会大大增加促进缺血组织中血管新生的作用。
方法:将C57BL/6J小鼠股动脉和股静脉切除后制作小鼠下肢缺血模型,分为EPO或SDF-1单独处理组和联合应用组。SDF-1应用方法为在缺血肌肉中立即注射NIH3T3/SDF-1细胞(10~6)以局部表达SDF-1,EPO应用方法为术后促红细胞生成素(EPO 1000IU/kg/day)每天腹腔注射,连续3天。小鼠缺血模型下肢血流灌注情况用激光多普勒扫描测定。下肢缺血手术后21天处死小鼠并用免疫组化和Western印迹方法分析缺血肌肉组织中细胞SDF-1表达,免疫方法检测缺血组织内CD34~+细胞,碱性磷酸酶染色方法评估毛细血管密度,原位凋亡测定试剂盒检测肌肉细胞的凋亡。全自动血液分析仪检测外周血液学参数以明确EPO对外周血细胞的影响。
结果:免疫组化和Wwestern印迹分析表明注射的NIH3T3/SDF-1细胞在缺血组织内生存并表达SDF-1。用SDF-1或EPO单独处理3周后缺血/非缺血肢体的血流灌注比分别增加到0.75±0.06和0.63±0.03,同注射生理盐水对照组相比增加明显(0.50±0.02,P＜0.05)。而联合应用SDF-1和EPO组小鼠缺血下肢血流灌注比增加更明显(0.89±0.08同单独一种处理相比P＜0.05)。在SDF-1和EPO处理组,CD34~+细胞增加,毛细血管密度增加和肌肉细胞凋亡减少均比其他组相比有意义(同其他组相比P＜0.05)。外周血红细胞数目和红细胞压积无明显增加。
结论:在小鼠下肢缺血模型中联合应用EPO增强EPCs动员和增加SDF-1调节的内皮祖细胞(EPCs)归巢可促进血管新生和增加血流灌注。同时,短期应用EPO并不增加红细胞数量和红细胞压积。
PartⅠIsolation and characterization of endothelial progenitor cells
Objective:To establish the culturing system of EPCs according to the former established protocols of our lab,and provide cell source for following experiments.
Method:Mononuclear cells(4×10~6) were isolated by density gradient centrifugation from rabbit peripheral blood(20 ml) plated on culture dishes coated with fibronectin (0.1%),and cultured in endothelial cell basal medium-2(EBM-2) supplemented with 20%fetal bovine serum(FBS) and Clonetics EGM-2 SingleQuots.The EPC were characterized by acetylated low density lipoprotein(DiI-acLDL) uptake,lectin binding(FITC-UEA-1),and immunochemical staining for CD34,CD133,CD45,von Willebrand factor(vWF),at 7 days after onset of culture.
Results:Attached spindle-like cells appeared after 3 days culture and became more and larger at 7 days of culture.Cord-like structure was observed.The positive rates of CD133,CD34,andⅧfactor of ex vivo expanded EPC at 7 days of culture were 83.11±3.46%,82.87±4.66%and 77.45±6.71%,respectively.CD45 is negative.The cells had the capacity to incorporate DiI-acLDL and FITC-UEA-1(＞90%).
Conclusion:EPCs have been shown to be present in circulation,and could be isolated and cultured from peripheral blood MNCs.
PartⅡ
Stromal cell-derived factor-1 effects on endothelial progenitor cell in vitro
Objective:To prepare NIH 3T3 transduced with the SDF-1αretroviral vector(NIH 3T3/SDF-1) and with LacZ retroviaral vector(NIH 3T3/LacZ) and investigate the effect of stromal cell-derived factor-1(SDF-1) secreted by NIH 3T3/SDF-1 on migration and apoptosis of ex vivo expanded EPCs.
Methods:Thaw the freezing NIH 3T3/SDF-1 cells and the SDF-1 concentration in the supernatant of cultured cells with or without EPO was measured with enzyme-linked immunosorbent assay(ELISA).Thaw the freezing NIH 3T3/LacZ cells and was conformed by theβ-Gal staining.Amodified Boyden chamber assay was used to determine the effect of secreted SDF-1 on EPC migration.Apoptosis of EPCs under influence of SDF-1 were investigated by stained with DAPI with or without L-NMMA.
Results:The freezing cells were thawed successfully and cells viability≥90%.NIH 3T3/SDF-1 cells produced 147±6 ng of SDF-1 per 10~6 cells in 24 h and EPO can not influence the expression of SDF-1 in NIH 3T3/SDF-1 cells.NIH3T3/LacZ cells were conformed by positiveβ-Gal staining.EPCs migrated more when they were co-cultured with NIH 3T3/SDF-1 than with unmodified NIH 3T3 cells(31±9 versus 13±4 migrated cells,respectively;P＜0.05).The migrated cells were significantly reduced to 16±4 when EPCs were cocultured with NIH 3T3/SDF-1 in the presence of L-NMMA(P＜0.05).Apoptosis was found in 30±7%of nutrient deprived EPCs co-cultured with NIH 3T3 cells.EPCs co-cultured with NIH 3T3/SDF-1 demonstrated a significant reduction in apoptosis(17±4%,P＜0.05) L-NMMA did not significantly affect apoptosis in EPCs co-cultured with NIH 3T3/SDF-1 cells(18±5%,P＞0.05).
Conclusion:NIH3T3/SDF-1 cells can secrete SDF-1 to induce EPC migration in vitro through NO pathway.Apoptosis of EPCs can be reduced by SDF-1 secreated by NIH3T3/SDF-1cells and NO is not involved in the inhibition of EPC apoptosis.
PartⅢErythropoietin with Stromal cell-derived factor-1 in therapeutic nevascularization of endothelial progenitor cells in ischemia limb
Objective:Erythropoietin(EPO) mobilizes bone marrow mononuclear cells into the peripheral circulation.Stromal cell-derived factor-1(SDF-1) enhances the homing of progenitor cells mobilized from the bone marrow and augments neovascularization in ischemic tissue.We hypothesize that SDF-1 will boost the pro-angiogenic effect of EPO.
Methods:NIH 3T3/SDF-1(10~6 cells) cells were injected into the ischemic muscles immediately after resection of the left femoral artery and vein of C57BL/6J mice. EPO(1000IU/kg/day) was injected intraperitioneally daily for 3 days after surgery. Blood perfusion was examined using a laser Doppler perfusion imaging system.Mice were sacrificed 21 days after surgery.Immunostaining and Western blot assay of the tissue lysates to confonfirm the cells in ischemia tissues and expressed SDF-1. Capillary density in the ischemia tissue were assessed with alkaline phosphatase staining,and the apoptosis of muscle cells was viewed using an in situ cell death detection kit.
Results:The perfusion ratio of ischemic/non-ischemic limb increased to 0.75±0.06 and 0.63±0.03 with the treatment of either SDF-1 or EPO only,respectively,3 weeks after surgery,which was significantly higher than the saline-injected control group (0.50±0.02,P＜0.05).Combined treatment with both SDF-1 and EPO resulted in an even better perfusion ratio of 0.89±0.08(P＜0.05 versus the single treatment groups). CD34~+ cells were detected with immunostaining,and Western blot assay showed that the injected NIH 3T3/SDF-1 survived and expressed SDF-1.More CD34~+ cells, increased capillary density,and less apoptotic muscle cells were found in both EPO and SDF-1 treated group(P＜0.05 versus other groups).
Conclusion:Combination of EPO-mediated progenitor cell mobilization and SDF-1-mediated homing of EPCs promotes neovascularization in the ischemic limb and increases the recovery of blood perfusion without increasing the number of red blood cells and hematocrit.
目的:利用实验室已建立的外周血内皮祖细胞(endothelial progenitor cells,EPCs)分离培养方案,建立EPCs的培养体系并进行细胞表型和功能的检测与鉴定,为后续的实验研究提供细胞来源。
方法:采集新西兰大白兔静脉外周血20ml,以密度梯度离心法获得单个核细胞,将细胞放入涂有0.1%纤连蛋白的培养皿中,在加有20%胎牛血清(FBS)和EGM-2 SingleQuots的内皮细胞基础培养基-2(EBM-2)中培养。于培养第7d应用免疫荧光检测细胞标志CD133,CD34,vWF,CD45抗原的表达;利用DiI-acLDL和FITC-UEA-1吸收试验鉴定内皮功能。
结果:单个核细胞在内皮条件下培养,48h后逐渐贴壁,第3d细胞呈梭形或不规则形,并逐渐变大,第7d梭形细胞增多,部分视野观察到梭形细胞首尾相连形成条索样结构。荧光显微镜观察CD133,CD34,vWF阳性率分别为83.11±3.46%,82.87±4.66%,77.45±6.71%,CD45阴性。并且,有＞90%的细胞吸收DiI-ac LDL和FITC-UEA-1。
结论:应用本研究方法从外周血途径分离、培养和扩增获得EPC,具有内皮祖细胞的特征和功能。
第二部分基质细胞衍生因子-1对内皮祖细胞的体外作用
目的:制备本实验室已冻存的病毒基因载体转导细胞NIH3T3/SDF-1和NIH3T3/LacZ细胞并检测细胞功能,利用其分泌基质细胞衍生因子-1(SDF-1)的特点研究对体外培养、扩增的EPC的影响。
方法:解冻NIH3T3细胞通过逆转录病毒转导SDF-1α基因和LacZ基因后制作能表达SDF-1的NIH3T3细胞(NIH3T3/SDF-1)和表达LacZ的NIH3T3/LacZ细胞。用ELASA法测定NIH3T3细胞,NIH3T3/SDF-1细胞在体外SDF-1表达情况,及存在EPO(10IU/ml)是对细胞表达SDF-1的影响,β-Gal染色法鉴定NIH3T3/LacZ细胞。用改良Boyden小室法检测NIH3T3/SDF-1细胞表达的SDF-1对内皮祖细胞EPCs体外迁移作用,DAPI染色法检测SDF-1对EPCs凋亡影响。
结果:冻存细胞可顺利解冻,培养细胞存活细胞率≥90%。转导入SDF-1表达载体的NIH 3T3/SDF-1细胞24小时可产生147±6 ng SDF-1/10~6细胞,转导入LacZ表达载体的NIH3T3/LacZ细胞可表达LacZ,细胞β-Gal染色阳性,为蓝色。EPO的存在并不能直接影响NIH3T3和NIH3T3/SDF-1细胞中SDF-1的表达。当EPCs与NIH3T3/SDF-1细胞共培养时同单独NIH3T3细胞共培养时相比迁移较多,(分别为31±9和13±4迁移细胞,P＜0.05)。并且,当在L-NMMA存在时,EPCs和NIH 3T3/SDF-1细胞共培养后迁移细胞明显减少为16±4(P＜0.05)。而与NIH 3T3/SDF-1细胞共培养的EPCs中凋亡发生率与同NIH 3T3细胞共培养的EPCs中凋亡发生率相比较低(分别为17±4%,30±7%P＜0.05)。L-NMMA的存在并不明显影响与NIH 3T3/SDF-1细胞共培养的EPCs中凋亡发生率(18±5%P＞0.05)。
结论:体外迁移实验表明EPC可在NIH3T3/SDF-1细胞分泌SDF-1的趋化作用下迁移,SDF-1可抑制EPCs凋亡。SDF-1迁移效应是通过一氧化氮(NO)途径,但NO没有参加SDF-1抑制EPC凋亡的过程。EPO并不影响NIH3T3/SDF-1细胞SDF-1的表达。本研究为下一步研究SDF-1在体内趋化EPC以及促血管新生的研究打下了必要的基础。
第三部分促红细胞生成素联合基质细胞衍生因子对小鼠缺血下肢血管新生的作用
目的:促红细胞生成素(EPO)可促进骨髓单核细胞动员到外周血中,基质细胞衍生因子1(SDF-1)可促进从骨髓动员后的祖细胞的在缺血组织中的归巢和血管新生。我们假设联合应用EPO和SDF-1会大大增加促进缺血组织中血管新生的作用。
方法:将C57BL/6J小鼠股动脉和股静脉切除后制作小鼠下肢缺血模型,分为EPO或SDF-1单独处理组和联合应用组。SDF-1应用方法为在缺血肌肉中立即注射NIH3T3/SDF-1细胞(10~6)以局部表达SDF-1,EPO应用方法为术后促红细胞生成素(EPO 1000IU/kg/day)每天腹腔注射,连续3天。小鼠缺血模型下肢血流灌注情况用激光多普勒扫描测定。下肢缺血手术后21天处死小鼠并用免疫组化和Western印迹方法分析缺血肌肉组织中细胞SDF-1表达,免疫方法检测缺血组织内CD34~+细胞,碱性磷酸酶染色方法评估毛细血管密度,原位凋亡测定试剂盒检测肌肉细胞的凋亡。全自动血液分析仪检测外周血液学参数以明确EPO对外周血细胞的影响。
结果:免疫组化和Wwestern印迹分析表明注射的NIH3T3/SDF-1细胞在缺血组织内生存并表达SDF-1。用SDF-1或EPO单独处理3周后缺血/非缺血肢体的血流灌注比分别增加到0.75±0.06和0.63±0.03,同注射生理盐水对照组相比增加明显(0.50±0.02,P＜0.05)。而联合应用SDF-1和EPO组小鼠缺血下肢血流灌注比增加更明显(0.89±0.08同单独一种处理相比P＜0.05)。在SDF-1和EPO处理组,CD34~+细胞增加,毛细血管密度增加和肌肉细胞凋亡减少均比其他组相比有意义(同其他组相比P＜0.05)。外周血红细胞数目和红细胞压积无明显增加。
结论:在小鼠下肢缺血模型中联合应用EPO增强EPCs动员和增加SDF-1调节的内皮祖细胞(EPCs)归巢可促进血管新生和增加血流灌注。同时,短期应用EPO并不增加红细胞数量和红细胞压积。
PartⅠIsolation and characterization of endothelial progenitor cells
Objective:To establish the culturing system of EPCs according to the former established protocols of our lab,and provide cell source for following experiments.
Method:Mononuclear cells(4×10~6) were isolated by density gradient centrifugation from rabbit peripheral blood(20 ml) plated on culture dishes coated with fibronectin (0.1%),and cultured in endothelial cell basal medium-2(EBM-2) supplemented with 20%fetal bovine serum(FBS) and Clonetics EGM-2 SingleQuots.The EPC were characterized by acetylated low density lipoprotein(DiI-acLDL) uptake,lectin binding(FITC-UEA-1),and immunochemical staining for CD34,CD133,CD45,von Willebrand factor(vWF),at 7 days after onset of culture.
Results:Attached spindle-like cells appeared after 3 days culture and became more and larger at 7 days of culture.Cord-like structure was observed.The positive rates of CD133,CD34,andⅧfactor of ex vivo expanded EPC at 7 days of culture were 83.11±3.46%,82.87±4.66%and 77.45±6.71%,respectively.CD45 is negative.The cells had the capacity to incorporate DiI-acLDL and FITC-UEA-1(＞90%).
Conclusion:EPCs have been shown to be present in circulation,and could be isolated and cultured from peripheral blood MNCs.
PartⅡ
Stromal cell-derived factor-1 effects on endothelial progenitor cell in vitro
Objective:To prepare NIH 3T3 transduced with the SDF-1αretroviral vector(NIH 3T3/SDF-1) and with LacZ retroviaral vector(NIH 3T3/LacZ) and investigate the effect of stromal cell-derived factor-1(SDF-1) secreted by NIH 3T3/SDF-1 on migration and apoptosis of ex vivo expanded EPCs.
Methods:Thaw the freezing NIH 3T3/SDF-1 cells and the SDF-1 concentration in the supernatant of cultured cells with or without EPO was measured with enzyme-linked immunosorbent assay(ELISA).Thaw the freezing NIH 3T3/LacZ cells and was conformed by theβ-Gal staining.Amodified Boyden chamber assay was used to determine the effect of secreted SDF-1 on EPC migration.Apoptosis of EPCs under influence of SDF-1 were investigated by stained with DAPI with or without L-NMMA.
Results:The freezing cells were thawed successfully and cells viability≥90%.NIH 3T3/SDF-1 cells produced 147±6 ng of SDF-1 per 10~6 cells in 24 h and EPO can not influence the expression of SDF-1 in NIH 3T3/SDF-1 cells.NIH3T3/LacZ cells were conformed by positiveβ-Gal staining.EPCs migrated more when they were co-cultured with NIH 3T3/SDF-1 than with unmodified NIH 3T3 cells(31±9 versus 13±4 migrated cells,respectively;P＜0.05).The migrated cells were significantly reduced to 16±4 when EPCs were cocultured with NIH 3T3/SDF-1 in the presence of L-NMMA(P＜0.05).Apoptosis was found in 30±7%of nutrient deprived EPCs co-cultured with NIH 3T3 cells.EPCs co-cultured with NIH 3T3/SDF-1 demonstrated a significant reduction in apoptosis(17±4%,P＜0.05) L-NMMA did not significantly affect apoptosis in EPCs co-cultured with NIH 3T3/SDF-1 cells(18±5%,P＞0.05).
Conclusion:NIH3T3/SDF-1 cells can secrete SDF-1 to induce EPC migration in vitro through NO pathway.Apoptosis of EPCs can be reduced by SDF-1 secreated by NIH3T3/SDF-1cells and NO is not involved in the inhibition of EPC apoptosis.
PartⅢErythropoietin with Stromal cell-derived factor-1 in therapeutic nevascularization of endothelial progenitor cells in ischemia limb
Objective:Erythropoietin(EPO) mobilizes bone marrow mononuclear cells into the peripheral circulation.Stromal cell-derived factor-1(SDF-1) enhances the homing of progenitor cells mobilized from the bone marrow and augments neovascularization in ischemic tissue.We hypothesize that SDF-1 will boost the pro-angiogenic effect of EPO.
Methods:NIH 3T3/SDF-1(10~6 cells) cells were injected into the ischemic muscles immediately after resection of the left femoral artery and vein of C57BL/6J mice. EPO(1000IU/kg/day) was injected intraperitioneally daily for 3 days after surgery. Blood perfusion was examined using a laser Doppler perfusion imaging system.Mice were sacrificed 21 days after surgery.Immunostaining and Western blot assay of the tissue lysates to confonfirm the cells in ischemia tissues and expressed SDF-1. Capillary density in the ischemia tissue were assessed with alkaline phosphatase staining,and the apoptosis of muscle cells was viewed using an in situ cell death detection kit.
Results:The perfusion ratio of ischemic/non-ischemic limb increased to 0.75±0.06 and 0.63±0.03 with the treatment of either SDF-1 or EPO only,respectively,3 weeks after surgery,which was significantly higher than the saline-injected control group (0.50±0.02,P＜0.05).Combined treatment with both SDF-1 and EPO resulted in an even better perfusion ratio of 0.89±0.08(P＜0.05 versus the single treatment groups). CD34~+ cells were detected with immunostaining,and Western blot assay showed that the injected NIH 3T3/SDF-1 survived and expressed SDF-1.More CD34~+ cells, increased capillary density,and less apoptotic muscle cells were found in both EPO and SDF-1 treated group(P＜0.05 versus other groups).
Conclusion:Combination of EPO-mediated progenitor cell mobilization and SDF-1-mediated homing of EPCs promotes neovascularization in the ischemic limb and increases the recovery of blood perfusion without increasing the number of red blood cells and hematocrit.
引文
1. Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006; 295:180-189.
2. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317-1324.
3. Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA 2006;295:547-553.
4. Crowther RG, Spinks WL, Leicht AS, Sangla K, Quigley F, Golledge J. Effects of a long-term exercise program on lower limb mobility, physiological responses,walking performance, and physical activity levels in patients with peripheral arterial disease. J Vasc Surg 2008;47:303-309.
5. Casey K, Tonnessen BH, Sternbergh WC 3rd, Money SR. Medical management of intermittent claudication. Vasc Endovascular Surg 2004;38:391-399.
6.Jeffrey M. Isner,Takayuki Asahara. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest. 1999 May 1; 103(9):1231 1236.
7.Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K,Razvi S, Walsh K, Symes JF.Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb.Lancet. 1996 Aug 10;348(9024):370-374.
8.Matoba S, Tatsumi T, Murohara T, Imaizumi T, Katsuda Y, Ito M, Saito Y, Uemura S, Suzuki H, Fukumoto S, Yamamoto Y, Onodera R, Teramukai S, Fukushima M,Matsubara H; TACT Follow-up Study Investigators. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J. 2008 Nov;156(5):1010-8.
9. Asahara T, Murohara T, Sullivan A, et al. Isolated of putative progenitor endothelial cells for angiogenesis. Science, 1997; 275:964-967
10. Tiwari A, Hamilton G, Seifalian AM,et al.Regarding "isolation of endothelial cells and their progenitor cells from human peripheral blood." J Vasc Surg.2002;35:827.
11.Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC,Hicklin DJ, Witte L, Moore MA, Rafii S. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors.Blood. 2000;95:952 958.
12. Hristov M, Erl W, Weber PC. Endothelial progenitor cells: mobilization,differentiation, and homing. Arterioscler Thromb Vase Biol. 2003 Jul 1;23(7):1185-9.
13.Strauer BE, Brehm M, Zeus T, K(?)stering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106:1913-1918.
14.Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P,Breidenbach .Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004;364:141-148.
15.Ratajczak MZ, Zuba-Surma E, Kucia M, Reca R, Wojakowski W, Ratajczak J.The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis.Leukemia. 2006 Nov;20(11):1915-1924.
16.Ara T, Tokoyoda K, Okamoto R, Koni PA, Nagasawa T.The role of CXCL12 in the organ-specific process of artery formation.Blood.2005 Apr 15;105(8):3155-61.
17. Petit I, Jin D, Rafii S. The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol.2007 Jul;28(7):299-307.
18. Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME,Capla JM, Galiano RD, Levine JP, Gurtner GC. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004 Aug;10(8):858-64.
19. Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM, Hooper AT,Amano H, Avecilla ST, Heissig B, Hattori K, Zhang F, Hicklin DJ, Wu Y, Zhu Z,Dunn A, Salari H, Werb Z, Hackett NR, Crystal RG, Lyden D, Rafii S.Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med. 2006 May;12(5):557-67.
20. Honold J, Lehmann R, Heeschen C, Walter DH, Assmus B, Sasaki K, Martin H,Haendeler J, Zeiher AM, Dimmeler S.Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol.2006 Oct;26(10):2238-43.
21.Hanlon PR, Fu P, Wright GL, Steenbergen C, Arcasoy MO, Murphy E.Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: role of protein kinase C and phosphatidylinositol 3-kinase signaling. FASEB J.2005 Aug;19(10):1323-5.
22. Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C,Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003 Aug 15;102(4):1340-6.
23.Lipsic E, van der Meer P, Voors AA, Westenbrink BD, van den Heuvel AF, de Boer HC, van Zonneveld AJ, Schoemaker RG, van Gilst WH, Zijlstra F, van Veldhuisen DJ. A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther.2006 Apr; 20(2):135-41.
1. Asahara T, Murohara T, Sullivan A, et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275(5302): 964-7.
2. Gill M, Dias S, Hattori K, et al.: Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 2001;88(2): 167-74.
3. Takahashi T, Kalka C, Masuda H, et al.: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5(4): 434-8.
4. Lyden D, Hattori K, Dias S, et al.: Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001; 7(11): 1194-201.
5. Murohara T, Ikeda H, Duan J, et al.: Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest 2000; 105(11):1527-36.
6. Peichev M, Naiyer AJ, Pereira D, et al.: Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000; 95(3): 952-8.
7. Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK:Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest 2003; 111(1):71-9.
8. Zammaretti P, Zisch AH: Adult 'endothelial progenitor cells'. Renewing vasculature.Int J Biochem Cell Biol 2005; 37(3): 493-503.
9. Rumpold H, Wolf D, Koeck R, Gunsilius E: Endothelial progenitor cells: a source for therapeutic vasculogenesis? J Cell Mol Med 2004; 8(4): 509-18.
10. Khoo CP, Pozzilli P, Alison MR: Endothelial progenitor cells and their potential therapeutic applications. Regen Med 2008; 3(6): 863-76.
11. Hur YG, Yun Y, Won J: Rosmarinic acid induces p561ck-dependent apoptosis in Jurkat and peripheral T cells via mitochondrial pathway independent from Fas/Fas ligand interaction. J Immunol 2004; 172(1): 79-87.
12. Lin Y, Weisdorf DJ, Solovey A, Hebbel RP: Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105(1): 71-7.
13. Kalka C, Masuda H, Takahashi T, et al.: Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 2000; 97(7): 3422-7.
14. Mukiibi M, Ela WP, Saez AE: Effect of ferrous iron on arsenate sorption to amorphous ferric hydroxide. Ann N Y Acad Sci 2008; 1140:335-45.
15. Akita T, Murohara T, Ikeda H, et al.: Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization. Lab Invest 2003; 83(1): 65-73.
16. Mizrak D, Brittan M, Alison MR: CD133: molecule of the moment. J Pathol 2008;214(1): 3-9.
17. Mukai N, Akahori T, Komaki M, et al.: A comparison of the tube forming potentials of early and late endothelial progenitor cells. Exp Cell Res 2008; 314(3):430-40.
18. Fadini GP, Baesso I, Albiero M, Sartore S, Agostini C, Avogaro A: Technical notes on endothelial progenitor cells: ways to escape from the knowledge plateau.Atherosclerosis 2008; 197(2): 496-503.
19. Nguyen VA, Furhapter C, Obexer P, Stossel H, Romani N, Sepp N: Endothelial cells from cord blood CD133(+)CD34(+) progenitors share phenotypic, functional and gene expression profile similarities with lymphatics. J Cell Mol Med 2008.
20. Shantsila E, Watson T, Tse HF, Lip GY: New insights on endothelial progenitor cell subpopulations and their angiogenic properties. J Am Coll Cardiol 2008; 51(6):669-71.
21. Heissig B, Hattori K, Dias S, et al.: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002;109(5): 625-37.
22. Rafii S, Meeus S, Dias S, et al.: Contribution of marrow-derived progenitors to vascular and cardiac regeneration. Semin Cell Dev Biol 2002; 13(1): 61-7.
23. Aicher A, Heeschen C, Mildner-Rihm C, et al.: Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 2003; 9(11):1370-6.
24. Brem H, Tomic-Canic M: Cellular and molecular basis of wound healing in diabetes. J Clin Invest 2007; 117(5): 1219-22.
25. Kucia M, Jankowski K, Reca R, et al.: CXCR4-SDF-1 signalling, locomotion,chemotaxis and adhesion. J Mol Histol 2004; 35(3): 233-45.
26. Heeschen C, Aicher A, Lehmann R, et al.: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102(4): 1340-6.
27. Ishizawa K, Kubo H, Yamada M, et al.: Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett 2004;556(1-3): 249-52.
28. Tamarat R, Silvestre JS, Le Ricousse-Roussanne S, et al.: Impairment in ischemia-induced neovascularization in diabetes: bone marrow mononuclear cell dysfunction and therapeutic potential of placenta growth factor treatment. Am J Pathol 2004; 164(2): 457-66.
29. Darland DC, D'Amore PA: Blood vessel maturation: vascular development comes of age. J Clin Invest 1999; 103(2): 157-8.
30. Melero-Martin JM, De Obaldia ME, Kang SY, et al.: Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 2008; 103(2): 194-202.
31. Kocher AA, Schuster MD, Szabolcs MJ, et al.: Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7(4):430-6.
32. Rafii S, Lyden D: Cancer. A few to flip the angiogenic switch. Science 2008;319(5860): 163-4.
33. Moreno PR, Purushothaman KR, Fuster V, et al.: Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 2004; 110(14): 2032-8.
34. Tepper OM, Galiano RD, Capla JM, et al.: Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002; 106(22): 2781-6.
35. Landmesser U, Drexler H: The clinical significance of endothelial dysfunction. Curr Opin Cardiol 2005; 20(6): 547-51.
36. Vagnucci AH, Jr., Li WW: Alzheimer's disease and angiogenesis. Lancet 2003;361(9357): 605-8.
37. Iwaguro H, Yamaguchi J, Kalka C, et al.: Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation 2002;105(6): 732-8.
38. Hiasa K, Ishibashi M, Ohtani K, et al.: Gene transfer of stromal cell-derived factor-1 alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004; 109(20): 2454-61.
39. Llevadot J, Murasawa S, Kureishi Y, et al.: HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Glin Invest 2001;108(3): 399-405.
40. Kong D, Melo LG, Mangi AA, et al.: Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation 2004;109(14): 1769-75.
41. Follenzi A, Benten D, Novikoff P, Faulkner L, Raut S, Gupta S: Transplanted endothelial cells repopulate the liver endothelium and correct the phenotype of hemophilia A mice. J Clin Invest 2008; 118(3): 935-45.
42. Qiu HY, Fujimori Y, Nishioka K, et al.: Postnatal neovascularization by endothelial progenitor cells immortalized with the simian virus 40T antigen gene. Int J Oncol 2006; 28(4): 815-21.
43. Kaushal S, Amiel GE, Guleserian KJ, et al.: Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 2001; 7(9):1035-40.
44. Dome B, Timar J, Dobos J, et al.: Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. Cancer Res 2006; 66(14): 7341-7.
45. Schmidt-Lucke C, Rossig L, Fichtlscherer S, et al.: Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111(22):2981-7.
46. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA: Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 2004; 56(4):549-80.
47. Kawamoto A, Asahara T, Losordo DW: Transplantation of endothelial progenitor cells for therapeutic neovascularization. Cardiovasc Radiat Med 2002; 3(3-4): 221-5.
48. Zohlnhofer D, Kastrati A, Schomig A: Stem cell mobilization by granulocyte-colony-stimulating factor in acute myocardial infarction: lessons from the REVIVAL-2 trial. Nat Clin Pract Cardiovasc Med 2007; 4 Suppl 1: S106-9.
49. Takahashi M, Nakamura T, Toba T, Kajiwara N, Kato H, Shimizu Y:Transplantation of endothelial progenitor cells into the lung to alleviate pulmonary hypertension in dogs. Tissue Eng 2004; 10(5-6): 771-9.
50. Nagaya N, Kangawa K, Kanda M, et al.: Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells.Circulation 2003; 108(7): 889-95.
51. Hess D, Li L, Martin M, et al.: Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 2003; 21(7): 763-70.
52. Alison MR, Choong C, Lim S: Application of liver stem cells for cell therapy. Semin Cell Dev Biol 2007; 18(6): 819-26.
53. Yannaki E, Anagnostopoulos A, Kapetanos D, et al.: Lasting amelioration in the clinical course of decompensated alcoholic cirrhosis with boost infusions of mobilized peripheral blood stem cells. Exp Hematol 2006; 34(11): 1583-7.
54. Brittan M, Chance V, Elia G, et al.: A regenerative role for bone marrow following experimental colitis: contribution to neovasculogenesis and myofibroblasts.Gastroenterology 2005; 128(7): 1984-95.
55. Hill JM, Zalos G, Halcox JP, et al.: Circulating endothelial progenitor cells,vascular function, and cardiovascular risk. N Engl J Med 2003; 348(7): 593-600.
1. Belperio JA, Keane MP, Arenberg DA, et al.: CXC chemokines in angiogenesis. J Leukoc Biol 2000; 68(1): 1-8.
2. Strieter RM, Polverini PJ, Kunkel SL, et al.: The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem 1995; 270(45): 27348-57.
3. Salcedo R, Wasserman K, Young HA, et al.: Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1 alpha. Am J Pathol 1999; 154(4): 1125-35.
4. Hiasa K, Ishibashi M, Ohtani K, et al.: Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004; 109(20): 2454-61.
5. Hattori K, Heissig B, Tashiro K, et al.: Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 2001; 97(11): 3354-60.
6. Heissig B, Hattori K, Dias S, et al.: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002;109(5): 625-37.
7. Grunewald M, Avraham I, Dor Y, et al.: VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 2006; 124(1): 175-89.
8. Yamaguchi J, Kusano KF, Masuo O, et al.: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003; 107(9): 1322-8.
9. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al.: Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 2004;10(8): 858-64.
10. Cottier-Fox MH, Lapidot T, Petit I, et al.: Stem cell mobilization. Hematology Am Soc Hematol Educ Program 2003:419-37.
11. Heeschen C, Aicher A, Lehmann R, et al.: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102(4): 1340-6.
12. Todaro G, Green H: Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J. Cell Bio. 1963; 17:299-313.
13. Kim CH, Broxmeyer HE: Chemokines: signal lamps for trafficking of T and B cells for development and effector function. J Leukoc Biol 1999; 65(1): 6-15.
14. Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G: Chemokines and their receptors in the central nervous system. Front Neuroendocrinol 2001; 22(3): 147-84.
15. Horuk R: Chemokine receptors. Cytokine Growth Factor Rev 2001; 12(4):313-35.
16. Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC: The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997; 185(1): 111-20.
17. Tashiro K, Tada H, Heilker R, Shirozu M, Nakano T, Honjo T: Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science 1993; 261(5121): 600-3.
18. Nagasawa T, Kikutani H, Kishimoto T: Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci U S A 1994; 91(6): 2305-9.
19. Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA: A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 1996; 184(3): 1101-9.
20. Sadir R, Baleux F, Grosdidier A, Imberty A, Lortat-Jacob H: Characterization of the stromal cell-derived factor-lalpha-heparin complex. J Biol Chem 2001; 276(11):8288-96.
21. Netelenbos T, van den Born J, Kessler FL, et al.: Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells.Leukemia 2003; 17(1): 175-84.
22. Berson JF, Long D, Doranz BJ, Rucker J, Jirik FR, Doms RW: A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains. J Virol 1996; 70(9): 6288-95.
23. Hashimoto Y, Ohashi R, Kurosawa Y, et al.: Pharmacologic profile of TA-606, a novel angiotensin II-receptor antagonist in the rat. J Cardiovasc Pharmacol 1998;31(4): 568-75.
24. Lapham CK, Zaitseva MB, Lee S, Romanstseva T, Golding H: Fusion of monocytes and macrophages with HIV-1 correlates with biochemical properties of CXCR4 and CCR5. Nat Med 1999; 5(3): 303-8.
25. Shirozu M, Nakano T, Inazawa J, et al.: Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics 1995; 28(3):495-500.
26. Fuchs E, Tumbar T, Guasch G: Socializing with the neighbors: stem cells and their niche. Cell 2004; 116(6): 769-78.
27. Wright DE, Bowman EP, Wagers AJ, Butcher EC, Weissman IL: Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. J Exp Med 2002;195(9): 1145-54.
28. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998; 393(6685): 595-9.
29. Bajetto A, Barbieri F, Dorcaratto A, et al.: Expression of CXC chemokine receptors 1-5 and their ligands in human glioma tissues: role of CXCR4 and SDF1 in glioma cell proliferation and migration. Neurochem Int 2006; 49(5): 423-32.
30. Simmons G, Reeves JD, Hibbitts S, et al.: Co-receptor use by HIV and inhibition of HIV infection by chemokine receptor ligands. Immunol Rev 2000; 177: 112-26.
31. Orlic D, Kajstura J, Chimenti S, et al.: Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410(6829): 701-5.
32. Tateishi-Yuyama E, Matsubara H, Murohara T, et al.: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360(9331): 427-35.
33. Peled A, Kollet O, Ponomaryov T, et al.: The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 2000;95(11): 3289-96.
34. Schober A, Knarren S, Lietz M, Lin EA, Weber C: Crucial role of stromal cell-derived factor-1 alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation 2003; 108(20): 2491-7.
35. Schioppa T, Uranchimeg B, Saccani A, et al.: Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 2003; 198(9): 1391-402.
36. Zernecke A, Schober A, Bot I, et al.: SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res 2005; 96(7): 784-91.
37. Massberg S, Konrad I, Schurzinger K, et al.: Platelets secrete stromal cell-derived factor lalpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.J Exp Med 2006;203(5):1221-33.
38.Jin DK,Shido K,Kopp HG,et al.:Cytokine-mediated deployment of SDF-1induces revascularization through recruitment of CXCR4+ hemangiocytes.Nat Med 2006;12(5):557-67.
1. Asahara T, Murohara T, Sullivan A, et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275(5302): 964-7.
2. Hristov M, Erl W, Weber PC: Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol 2003; 23(7): 1185-9.
3. Murohara T, Ikeda H, Duan J, et al.: Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest 2000; 105(11):1527-36.
4. Kamihata H, Matsubara H, Nishiue T, et al.: Improvement of collateral perfiision and regional function by implantation of peripheral blood mononuclear cells into ischemic hibernating myocardium. Arterioscler Thromb Vasc Biol 2002; 22(11):1804-10.
5. Shintani S, Murohara T, Ikeda H, et al.: Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation 2001;103(6): 897-903.
6. Masuda H, Asahara T: Post-natal endothelial progenitor cells for neovascularization in tissue regeneration. Cardiovasc Res 2003; 58(2): 390-8.
7. Asahara T, Masuda H, Takahashi T, et al.: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85(3): 221-8.
8. Lee SH, Wolf PL, Escudero R, et al.: Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N Engl J Med 2000; 342(9): 626-33.
9. Pillarisetti K, Gupta SK: Cloning and relative expression analysis of rat stromal cell derived factor-1 (SDF-1)1: SDF-1 alpha mRNA is selectively induced in rat model of myocardial infarction. Inflammation 2001; 25(5): 293-300.
10. Shintani S, Murohara T, Ikeda H, et al.: Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 2001; 103(23): 2776-9.
11. Takahashi T, Kalka C, Masuda H, et al.: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5(4): 434-8.
12. Kocher AA, Schuster MD, Szabolcs MJ, et al.: Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7(4): 430-6.
13. Minamino K, Adachi Y, Okigaki M, et al.: Macrophage colony-stimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization. Stem Cells 2005; 23(3): 347-54.
14. Bahlmann FH, De Groot K, Spandau JM, et al.: Erythropoietin regulates endothelial progenitor cells. Blood 2004; 103(3): 921-6.
15. Moore MA, Hattori K, Heissig B, et al.: Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1. Ann N Y Acad Sci 2001; 938: 36-45; discussion 45-7.
16. van Royen N, Schirmer SH, Atasever B, et al.: START Trial: a pilot study on STimulation of ARTeriogenesis using subcutaneous application of granulocyte-macrophage colony-stimulating factor as a new treatment for peripheral vascular disease. Circulation 2005; 112(7): 1040-6.
17. Honold J, Lehmann R, Heeschen C, et al.: Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol 2006; 26(10):2238-43.
18. Maiese K, Li F, Chong ZZ: New avenues of exploration for erythropoietin. Jama 2005; 293(1): 90-5.
19. Prass K, Scharff A, Ruscher K, et al.: Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 2003; 34(8): 1981-6.
20. Wright GL, Hanlon P, Amin K, Steenbergen C, Murphy E, Arcasoy MO:Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury. Faseb J 2004; 18(9): 1031-3.
21. Hanlon PR, Fu P, Wright GL, Steenbergen C, Arcasoy MO, Murphy E:Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: role of protein kinase C and phosphatidylinositol 3-kinase signaling. Faseb J 2005; 19(10): 1323-5.
22. Heeschen C, Aicher A, Lehmann R, et al.: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102(4): 1340-6.
23. Westenbrink BD, Lipsic E, van der Meer P, et al.: Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J 2007; 28(16): 2018-27.
24. Lipsic E, van der Meer P, Voors AA, et al.: A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther 2006; 20(2):135-41.
25. Grunewald M, Avraham I, Dor Y, et al.: VEGF-induced adult neovascularization:recruitment, retention, and role of accessory cells. Cell 2006; 124(1): 175-89.
26. Yamaguchi J, Kusano KF, Masuo O, et al.: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003; 107(9): 1322-8.
27. Hiasa K, Ishibashi M, Ohtani K, et al.: Gene transfer of stromal cell-derived factor-1 alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004; 109(20): 2454-61.
28. Woo YJ, Grand TJ, Berry MF, et al.: Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. J Thorac Cardiovasc Surg 2005; 130(2): 321-9.
29. Atluri P, Liao GP, Panlilio CM, et al.: Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Ann Thorac Surg 2006;81(5): 1728-36.
30. Misao Y, Takemura G, Arai M, et al.: Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-CSF.Cardiovasc Res 2006; 71(3): 455-65.
3
1. Niiyama H, Kai H, Yamamoto T, et al.: Roles of endogenous monocyte chemoattractant protein-1 in ischemia-induced neovascularization. J Am Coll Cardiol 2004; 44(3): 661-6.
32. Dokun AO, Keum S, Hazarika S, et al.: A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical hindlimb ischemia. Circulation 2008; 117(9): 1207-15.
33. Kuhlmann CR, Schaefer CA, Reinhold L, Tillmanns H, Erdogan A: Signalling mechanisms of SDF-induced endothelial cell proliferation and migration. Biochem Biophys Res Commun 2005; 335(4): 1107-14.
34. Guo Y, Hangoc G, Bian H, Pelus LM, Broxmeyer HE: SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells. Stem Cells 2005; 23(9): 1324-32.
35. Brunner S, Winogradow J, Huber BC, et al.: Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. Faseb J 2009; 23(2): 351-61.
36. Brunner S, Huber BC, Fischer R, et al.: G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells. Exp Hematol 2008; 36(6): 695-702.
37. Askari AT, Unzek S, Popovic ZB, et al.: Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 2003;362(9385): 697-703.
38. Tateishi-Yuyama E, Matsubara H, Murohara T, et al.: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360(9331): 427-35.
39. Kawamoto A, Asahara T, Losordo DW: Transplantation of endothelial progenitor cells for therapeutic neovascularization. Cardiovasc Radiat Med 2002; 3(3-4): 221-5.
40. Landmesser U, Drexler H: The clinical significance of endothelial dysfunction.Curr Opin Cardiol 2005; 20(6): 547-51.
41. Uchida E, Morimoto K, Kawasaki N, Izaki Y, Abdu Said A, Hayakawa T: Effect of active oxygen radicals on protein and carbohydrate moieties of recombinant human erythropoietin. Free Radic Res 1997; 27(3): 311-23.
42. Chong ZZ, Kang JQ, Maiese K: Hematopoietic factor erythropoietin fosters neuroprotection through novel signal transduction cascades. J Cereb Blood Flow Metab 2002; 22(5): 503-14.
43. Chong ZZ, Kang JQ, Maiese K: Angiogenesis and plasticity: role of erythropoietin in vascular systems. J Hematother Stem Cell Res 2002; 11(6): 863-71.
44. Gene S, Koroglu TF, Genc K: Erythropoietin as a novel neuroprotectant. Restor Neurol Neurosci 2004; 22(2): 105-19.
45. Anagnostou A, Liu Z, Steiner M, et al.: Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci U S A 1994; 91(9): 3974-8.
46. Ribatti D, Presta M, Vacca A, et al.: Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 1999; 93(8): 2627-36.
47. Hewitson KS, McNeill LA, Schofield CJ: Modulating the hypoxia-inducible factor signaling pathway: applications from cardiovascular disease to cancer. Curr Pharm Des 2004; 10(8): 821-33.
48. Sakamaki K: Regulation of endothelial cell death and its role in angiogenesis and vascular regression. Curr Neurovasc Res 2004; 1(4): 305-15.
49. Maiese K, Chong ZZ: Insights into oxidative stress and potential novel therapeutic targets for Alzheimer disease. Restor Neurol Neurosci 2004; 22(2): 87-104.
50. Kawakami M, Sekiguchi M, Sato K, Kozaki S, Takahashi M: Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia. J Biol Chem 2001; 276(42): 39469-75.
51. Chong ZZ, Li F, Maiese K: Activating Akt and the brain's resources to drive cellular survival and prevent inflammatory injury. Histol Histopathol 2005; 20(1):299-315.
52. Chong ZZ, Kang JQ, Maiese K: Erythropoietin is a novel vascular protectant through activation of Aktl and mitochondrial modulation of cysteine proteases. Circulation 2002; 106(23): 2973-9.
53. Chong ZZ, Kang JQ, Maiese K: Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. J Cereb Blood Flow Metab 2003; 23(3): 320-30.
54. Somervaille TC, Linch DC, Khwaja A: Growth factor withdrawal from primary human erythroid progenitors induces apoptosis through a pathway involving glycogen synthase kinase-3 and Bax. Blood 2001; 98(5): 1374-81.
55. George J, Goldstein E, Abashidze A, et al.: Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. Cardiovasc Res 2005; 68(2): 299-306.
56. Carlini RG, Reyes AA, Rothstein M: Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int 1995; 47(3): 740-5.
57. Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck KH: Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 2002; 64(2): 326-33.
58. Nakano M, Satoh K, Fukumoto Y, et al.: Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice. Circ Res 2007; 100(5): 662-9.
59. Erslev AJ, Caro J: Erythropoietin: from mountain top to bedside. Adv Exp Med Biol 1989; 271:1-7.
60. Hayashi T, Suzuki A, Shoji T, et al.: Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure. Am J Kidney Dis 2000; 35(2): 250-6.
61. Jelkmann W: Biology of erythropoietin. Clin Investig 1994; 72(6 Suppl): S3-10.
62. Hebert PC, Wells G, Blajchman MA, et al.: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340(6): 409-17.
63. Rao SV, Stamler JS: Erythropoietin, anemia, and orthostatic hypotension: the evidence mounts. Clin Auton Res 2002; 12(3): 141-3.
64. Grimm C, Wenzel A, Groszer M, et al.: HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med 2002; 8(7):718-24.
65. Digicaylioglu M, Lipton SA: Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 2001; 412(6847):641-7.
66. Ihle JN: Cytokine receptor signalling. Nature 1995; 377(6550): 591-4.
67. Wojchowski DM, Gregory RC, Miller CP, Pandit AK, Pircher TJ: Signal transduction in the erythropoietin receptor system. Exp Cell Res 1999; 253(1):143-56.
68. Palmer LA, Gaston B, Johns RA: Normoxic stabilization of hypoxia-inducible factor-1 expression and activity: redox-dependent effect of nitrogen oxides. Mol Pharmacol 2000; 58(6): 1197-203.
69. Maiese K, Li F, Chong ZZ: Erythropoietin in the brain: can the promise to protect be fulfilled? Trends Pharmacol Sci 2004; 25(11): 577-83.
70. Jelkmann W, Wagner K: Beneficial and ominous aspects of the pleiotropic action of erythropoietin. Ann Hematol 2004; 83(11): 673-86.
71. van der Meer P, Voors AA, Lipsic E, Smilde TD, van Gilst WH, van Veldhuisen DJ: Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol 2004; 44(1): 63-7.
72. Henry DH, Bowers P, Romano MT, Provenzano R: Epoetin alfa. Clinical evolution of a pleiotropic cytokine. Arch Intern Med 2004; 164(3): 262-76.
73. Ajmani RS, Metter EJ, Jaykumar R, et al.: Hemodynamic changes during aging associated with cerebral blood flow and impaired cognitive function. Neurobiol Aging 2000; 21(2): 257-69.
74. Moulton KS, Vakili K, Zurakowski D, et al.: Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci U S A 2003; 100(8): 4736-41.
75. Bennett CL, Luminari S, Nissenson AR, et al.: Pure red-cell aplasia and epoetin therapy. N Engl J Med 2004; 351(14): 1403-8.
76. Verdier F, Walrafen P, Hubert N, et al.: Proteasomes regulate the duration of erythropoietin receptor activation by controlling down-regulation of cell surface receptors. J Biol Chem 2000; 275(24): 18375-81.
77. Moon C, Krawczyk M, Ahn D, et al.: Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A 2003; 100(20): 11612-7.
78. Lipsic E, Westenbrink BD, van der Meer P, et al.: Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit. Eur J Heart Fail 2008; 10(1): 22-9.
79. Leist M, Ghezzi P, Grasso G, et al.: Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 2004; 305(5681): 239-42.
80. Moon C, Krawczyk M, Paik D, et al.: Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties. J Pharmacol Exp Ther 2006; 316(3): 999-1005.
81. Fiordaliso F, Chimenti S, Staszewsky L, et al.: A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury. Proc Natl Acad Sci U S A 2005; 102(6): 2046-51.
1.Criqui MH,Fronek A,Barrett-Connor E,Klauber MR,Gabriel S,Goodman D:The prevalence of peripheral arterial disease in a defined population.Circulation 1985;71(3):510-5.
2.Murabito JM,D'Agostino RB,Silbershatz H,Wilson WF:Intermittent claudication.A risk profile from The Framingham Heart Study.Circulation 1997;96(1):44-9.
3.Dormandy J,Heeck L,Vig S:The fate of patients with critical leg ischemia.Semin Vasc Surg 1999;12(2):142-7.
4.Norgren L,Hiatt WR,Dormandy JA,Nehler MR,Harris KA,Fowkes FG:Inter-Society Consensus for the Management of Peripheral Arterial Disease(TASC Ⅱ). J Vasc Surg 2007; 45 Suppl S: S5-67.
5. Adam DJ, Beard JD, Cleveland T, et al.: Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet 2005;366(9501): 1925-34.
6. Baumgartner I, Schainfeld R, Graziani L: Management of peripheral vascular disease. Annu Rev Med 2005; 56:249-72.
7. Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nat Med 2000; 6(4):389-95.
8. Saniabadi AR, Marney Y, Belch JJ, et al.: Further evidence that the residual vWf:Ag in porcine FVIILC induces human platelet aggregation. Haemostasis 1990;20(5): 289-95.
9. Schaper W, Scholz D: Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol 2003; 23(7): 1143-51.
10. Heil M, Schaper W: Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res 2004; 95(5): 449-58.
11. Heil M, Eitenmuller I, Schmitz-Rixen T, Schaper W: Arteriogenesis versus angiogenesis: similarities and differences. J Cell Mol Med 2006; 10(1): 45-55.
12. Babiak A, Schumm AM, Wangler C, et ah: Coordinated activation of VEGFR-1 and VEGFR-2 is a potent arteriogenic stimulus leading to enhancement of regional perfusion. Cardiovasc Res 2004; 61(4): 789-95.
13. Panchal VR, Rehman J, Nguyen AT, et al.: Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease. J Am Coll Cardiol 2004; 43(8): 1383-7.
14. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 1(1): 27-31.
15. Wang GL, Semenza GL: General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A 1993; 90(9): 4304-8.
16. Kelly BD, Hackett SF, Hirota K, et al.: Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res 2003; 93(11):1074-81.
17. Rissanen TT, Korpisalo P, Markkanen JE, et al.: Blood flow remodels growing vasculature during vascular endothelial growth factor gene therapy and determines between capillary arterialization and sprouting angiogenesis. Circulation 2005; 112(25): 3937-46.
18. Asahara T, Masuda H, Takahashi T, et al.: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85(3): 221-8.
19. Isner JM, Asahara T: Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest 1999; 103(9): 1231-6.
20. Takeshita S, Zheng LP, Brogi E, et al.: Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 1994; 93(2): 662-70.
21. Losordo DW, Dimmeler S: Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part I: angiogenic cytokines. Circulation 2004; 109(21): 2487-91.
22. Tio RA, Wijpkema JS, Tan ES, et al.: Functional characteristics of coronary vasomotor function following intramyocardial gene therapy with naked DNA encoding for vascular endothelial growth factorl65. Endothelium 2005; 12(3): 103-6.
23. Bahlmann FH, De Groot K, Spandau JM, et al.: Erythropoietin regulates endothelial progenitor cells. Blood 2004; 103(3): 921-6.
24. Kalka C, Masuda H, Takahashi T, et al.: Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects.Circ Res 2000; 86(12): 1198-202.
25. Henry TD: Therapeutic angiogenesis. Bmj 1999; 318(7197): 1536-9.
26. Klagsbrun M, D'Amore PA: Vascular endothelial growth factor and its receptors.Cytokine Growth Factor Rev 1996; 7(3): 259-70.
27. Gitay-Goren H, Cohen T, Tessler S, et al.: Selective binding of VEGF121 to one of the three vascular endothelial growth factor receptors of vascular endothelial cells.J Biol Chem 1996; 271(10): 5519-23.
28. Shalaby F, Rossant J, Yamaguchi TP, et al.: Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995; 376(6535): 62-6.
29. Powers CJ, McLeskey SW, Wellstein A: Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 2000; 7(3): 165-97.
30. Couchman JR: Syndecans: proteoglycan regulators of cell-surface microdomains? Nat Rev Mol Cell Biol 2003; 4(12): 926-37.
31. Bauters C, Six I, Meurice T, Van Belle E: Growth factors and endothelial dysfunction. Drugs 1999; 59 Spec No: 11-5.
32. Detillieux KA, Sheikh F, Kardami E, Cattini PA: Biological activities of fibroblast growth factor-2 in the adult myocardium. Cardiovasc Res 2003; 57(1): 8-19.
33. Asahara T, Bauters C, Zheng LP, et al.: Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation 1995; 92(9 Suppl): 11365-71.
34. Ferrara N, Houck K, Jakeman L, Leung DW: Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992; 13(1):18-32.
35. Unger EF, Goncalves L, Epstein SE, et al.: Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris. Am J Cardiol 2000; 85(12): 1414-9.
36. Lazarous DF, Unger EF, Epstein SE, et al.: Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial. J Am Coll Cardiol 2000; 36(4): 1239-44.
37. Cooper LT, Jr., Hiatt WR, Creager MA, et al.: Proteinuria in a placebo-controlled study of basic fibroblast growth factor for intermittent claudication. Vasc Med 2001;6(4): 235-9.
38. Simons M, Bonow RO, Chronos NA, et al.: Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary. Circulation 2000; 102(11):E73-86.
39. Wolff JA, Malone RW, Williams P, et al.: Direct gene transfer into mouse muscle in vivo. Science 1990; 247(4949 Pt 1): 1465-8.
40. Mulligan RC: The basic science of gene therapy. Science 1993; 260(5110):926-32.
41. Gao X, Huang L: Cationic liposome-mediated gene transfer. Gene Ther 1995;2(10): 710-22.
42. Yla-Herttuala S, Alitalo K: Gene transfer as a tool to induce therapeutic vascular growth. Nat Med 2003; 9(6): 694-701.
43. Dor Y, Djonov V, Abramovitch R, et al.: Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. Embo J 2002;21(8): 1939-47.
44. Baumgartner I, Pieczek A, Manor O, et al.: Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998; 97(12): 1114-23.
45. Baumgartner I, Rauh G, Pieczek A, et al.: Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor. Ann Intern Med 2000; 132(11): 880-4.
46. Isner JM, Baumgartner I, Rauh G, et al.: Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg 1998; 28(6): 964-73; discussion 73-5.
47. Losordo DW, Vale PR, Symes JF, et al.: Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 1998; 98(25): 2800-4.
48. Shyu KG, Chang H, Wang BW, Kuan P: Intramuscular vascular endothelial growth factor gene therapy in patients with chronic critical leg ischemia. Am J Med 2003; 114(2): 85-92.
49. Comerota AJ, Throm RC, Miller KA, et al.: Naked plasmid DNA encoding fibroblast growth factor type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: preliminary results of a phase I trial. J Vase Surg 2002; 35(5):930-6.
50. Nikol S, Baumgartner I, Van Belle E, et al.: Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther 2008; 16(5): 972-8.
51. Makinen K, Manninen H, Hedman M, et al.: Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study. Mol Ther 2002; 6(1):127-33.
52. Rajagopalan S, Mohler ER, 3rd, Lederman RJ, et al.: Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication.Circulation 2003; 108(16): 1933-8.
53. Kalka C, Baumgartner I: Gene and stem cell therapy in peripheral arterial occlusive disease. Vasc Med 2008; 13(2): 157-72.
54. Kusumanto YH, van Weel V, Mulder NH, et al.: Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. Hum Gene Ther 2006; 17(6): 683-91.
55. Horowitz JR, Rivard A, van der Zee R, et al.: Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension.Evidence for a maintenance role in quiescent adult endothelium. Arterioscler Thromb Vasc Biol 1997; 17(11): 2793-800.
56. Schwarz ER, Speakman MT, Patterson M, et al.: Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat~angiogenesis and angioma formation. J Am Coll Cardiol 2000; 35(5): 1323-30.
57. Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM: VEGF gene delivery to muscle: potential role for vasculogenesis in adults. Mol Cell 1998; 2(5): 549-58.
58. Tio RA, Tkebuchava T, Scheuermann TH, et al.: Intramyocardial gene therapy with naked DNA encoding vascular endothelial growth factor improves collateral flow to ischemic myocardium. Hum Gene Ther 1999; 10(18): 2953-60.
59. Vale PR, Isner JM, Rosenfield K: Therapeutic angiogenesis in critical limb and myocardial ischemia. J Interv Cardiol 2001; 14(5): 511-28.
60. Isner JM, Vale PR, Symes JF, Losordo DW: Assessment of risks associated with cardiovascular gene therapy in human subjects. Circ Res 2001; 89(5): 389-400.
61. Inoue M, Itoh H, Ueda M, et al.: Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis. Circulation 1998; 98(20): 2108-16.
62. Isner JM: Cancer and atherosclerosis: the broad mandate of angiogenesis.Circulation 1999; 99(13): 1653-5.
63. Odorico JS, Kaufman DS, Thomson JA: Multilineage differentiation from human embryonic stem cell lines. Stem Cells 2001; 19(3): 193-204.
64. Teramoto K, Hara Y, Kumashiro Y, et al.: Teratoma formation and hepatocyte differentiation in mouse liver transplanted with mouse embryonic stem cell-derived embryoid bodies. Transplant Proc 2005; 37(1): 285-6.
65. Asahara T, Murohara T, Sullivan A, et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275(5302): 964-7.
66. Lin Y, Weisdorf DJ, Solovey A, Hebbel RP: Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105(1): 71-7.
67. Rehman J, Li J, Orschell CM, March KL: Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.Circulation 2003; 107(8): 1164-9.
68. Heissig B, Hattori K, Dias S, et al.: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002;109(5): 625-37.
69. Aicher A, Heeschen C, Mildner-Rihm C, et al.: Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 2003; 9(11):1370-6.
70. Kalka C, Masuda H, Takahashi T, et al.: Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 2000; 97(7): 3422-7.
71. Murayama T, Tepper OM, Silver M, et al.: Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 2002; 30(8): 967-72.
72. Crosby JR, Kaminski WE, Schatteman G, et al.: Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ Res 2000;87(9): 728-30.
73. Kawamoto A, Iwasaki H, Kusano K, et al.: CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 2006; 114(20): 2163-9.
74. Jackson KA, Majka SM, Wang H, et al.: Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001; 107(11): 1395-402.
75. Assmus B, Schachinger V, Teupe C, et al.: Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI).Circulation 2002; 106(24): 3009-17.
76. Assmus B, Honold J, Schachinger V, et al.: Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006; 355(12): 1222-32.
77. Lunde K, Solheim S, Aakhus S, et al.: Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355(12):1199-209.
78. Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S: Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction.Eur Heart J 2007; 28(6): 766-72.
79. Tateishi-Yuyama E, Matsubara H, Murohara T, et al.: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360(9331): 427-35.
80. Higashi Y, Kimura M, Hara K, et al.: Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation 2004; 109(10): 1215-8.
81. Ross R: Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340(2):115-26.
82. Seiler C, Pohl T, Wustmann K, et al.: Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study. Circulation 2001;104(17): 2012-7.
83. Heeschen C, Lehmann R, Honold J, et al.: Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 2004; 109(13): 1615-22.
84. Griese DP, Achatz S, Batzlsperger CA, et al.: Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells. Cardiovasc Res 2003; 58(2): 469-77.
85. Hu Y, Davison F, Zhang Z, Xu Q: Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells.Circulation 2003; 108(25): 3122-7.
86. George J, Afek A, Abashidze A, et al.: Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2005; 25(12): 2636-41.
87. Silvestre JS, Gojova A, Brun V, et al.: Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation 2003; 108(23):2839-42.
88. Sata M: Circulating vascular progenitor cells contribute to vascular repair, remodeling, and lesion formation. Trends Cardiovasc Med 2003; 13(6): 249-53.
89. Werner N, Kosiol S, Schiegl T, et al.: Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353(10): 999-1007.
90. Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW: Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.Circulation 2004; 109(25): 3154-7.
91. Spring H, Schuler T, Arnold B, Hammerling GJ, Ganss R: Chemokines direct endothelial progenitors into tumor neovessels. Proc Natl Acad Sci U S A 2005;102(50): 18111-6.
92. Davidoff AM, Ng CY, Brown P, et al.: Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin Cancer Res 2001; 7(9): 2870-9.
93. Schuch G, Heymach JV, Nomi M, et al.: Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells. Cancer Res 2003; 63(23): 8345-50.
2. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317-1324.
3. Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA 2006;295:547-553.
4. Crowther RG, Spinks WL, Leicht AS, Sangla K, Quigley F, Golledge J. Effects of a long-term exercise program on lower limb mobility, physiological responses,walking performance, and physical activity levels in patients with peripheral arterial disease. J Vasc Surg 2008;47:303-309.
5. Casey K, Tonnessen BH, Sternbergh WC 3rd, Money SR. Medical management of intermittent claudication. Vasc Endovascular Surg 2004;38:391-399.
6.Jeffrey M. Isner,Takayuki Asahara. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest. 1999 May 1; 103(9):1231 1236.
7.Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K,Razvi S, Walsh K, Symes JF.Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb.Lancet. 1996 Aug 10;348(9024):370-374.
8.Matoba S, Tatsumi T, Murohara T, Imaizumi T, Katsuda Y, Ito M, Saito Y, Uemura S, Suzuki H, Fukumoto S, Yamamoto Y, Onodera R, Teramukai S, Fukushima M,Matsubara H; TACT Follow-up Study Investigators. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J. 2008 Nov;156(5):1010-8.
9. Asahara T, Murohara T, Sullivan A, et al. Isolated of putative progenitor endothelial cells for angiogenesis. Science, 1997; 275:964-967
10. Tiwari A, Hamilton G, Seifalian AM,et al.Regarding "isolation of endothelial cells and their progenitor cells from human peripheral blood." J Vasc Surg.2002;35:827.
11.Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC,Hicklin DJ, Witte L, Moore MA, Rafii S. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors.Blood. 2000;95:952 958.
12. Hristov M, Erl W, Weber PC. Endothelial progenitor cells: mobilization,differentiation, and homing. Arterioscler Thromb Vase Biol. 2003 Jul 1;23(7):1185-9.
13.Strauer BE, Brehm M, Zeus T, K(?)stering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106:1913-1918.
14.Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P,Breidenbach .Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004;364:141-148.
15.Ratajczak MZ, Zuba-Surma E, Kucia M, Reca R, Wojakowski W, Ratajczak J.The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis.Leukemia. 2006 Nov;20(11):1915-1924.
16.Ara T, Tokoyoda K, Okamoto R, Koni PA, Nagasawa T.The role of CXCL12 in the organ-specific process of artery formation.Blood.2005 Apr 15;105(8):3155-61.
17. Petit I, Jin D, Rafii S. The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol.2007 Jul;28(7):299-307.
18. Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME,Capla JM, Galiano RD, Levine JP, Gurtner GC. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004 Aug;10(8):858-64.
19. Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM, Hooper AT,Amano H, Avecilla ST, Heissig B, Hattori K, Zhang F, Hicklin DJ, Wu Y, Zhu Z,Dunn A, Salari H, Werb Z, Hackett NR, Crystal RG, Lyden D, Rafii S.Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med. 2006 May;12(5):557-67.
20. Honold J, Lehmann R, Heeschen C, Walter DH, Assmus B, Sasaki K, Martin H,Haendeler J, Zeiher AM, Dimmeler S.Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol.2006 Oct;26(10):2238-43.
21.Hanlon PR, Fu P, Wright GL, Steenbergen C, Arcasoy MO, Murphy E.Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: role of protein kinase C and phosphatidylinositol 3-kinase signaling. FASEB J.2005 Aug;19(10):1323-5.
22. Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C,Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003 Aug 15;102(4):1340-6.
23.Lipsic E, van der Meer P, Voors AA, Westenbrink BD, van den Heuvel AF, de Boer HC, van Zonneveld AJ, Schoemaker RG, van Gilst WH, Zijlstra F, van Veldhuisen DJ. A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther.2006 Apr; 20(2):135-41.
1. Asahara T, Murohara T, Sullivan A, et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275(5302): 964-7.
2. Gill M, Dias S, Hattori K, et al.: Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 2001;88(2): 167-74.
3. Takahashi T, Kalka C, Masuda H, et al.: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5(4): 434-8.
4. Lyden D, Hattori K, Dias S, et al.: Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001; 7(11): 1194-201.
5. Murohara T, Ikeda H, Duan J, et al.: Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest 2000; 105(11):1527-36.
6. Peichev M, Naiyer AJ, Pereira D, et al.: Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000; 95(3): 952-8.
7. Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK:Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest 2003; 111(1):71-9.
8. Zammaretti P, Zisch AH: Adult 'endothelial progenitor cells'. Renewing vasculature.Int J Biochem Cell Biol 2005; 37(3): 493-503.
9. Rumpold H, Wolf D, Koeck R, Gunsilius E: Endothelial progenitor cells: a source for therapeutic vasculogenesis? J Cell Mol Med 2004; 8(4): 509-18.
10. Khoo CP, Pozzilli P, Alison MR: Endothelial progenitor cells and their potential therapeutic applications. Regen Med 2008; 3(6): 863-76.
11. Hur YG, Yun Y, Won J: Rosmarinic acid induces p561ck-dependent apoptosis in Jurkat and peripheral T cells via mitochondrial pathway independent from Fas/Fas ligand interaction. J Immunol 2004; 172(1): 79-87.
12. Lin Y, Weisdorf DJ, Solovey A, Hebbel RP: Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105(1): 71-7.
13. Kalka C, Masuda H, Takahashi T, et al.: Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 2000; 97(7): 3422-7.
14. Mukiibi M, Ela WP, Saez AE: Effect of ferrous iron on arsenate sorption to amorphous ferric hydroxide. Ann N Y Acad Sci 2008; 1140:335-45.
15. Akita T, Murohara T, Ikeda H, et al.: Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization. Lab Invest 2003; 83(1): 65-73.
16. Mizrak D, Brittan M, Alison MR: CD133: molecule of the moment. J Pathol 2008;214(1): 3-9.
17. Mukai N, Akahori T, Komaki M, et al.: A comparison of the tube forming potentials of early and late endothelial progenitor cells. Exp Cell Res 2008; 314(3):430-40.
18. Fadini GP, Baesso I, Albiero M, Sartore S, Agostini C, Avogaro A: Technical notes on endothelial progenitor cells: ways to escape from the knowledge plateau.Atherosclerosis 2008; 197(2): 496-503.
19. Nguyen VA, Furhapter C, Obexer P, Stossel H, Romani N, Sepp N: Endothelial cells from cord blood CD133(+)CD34(+) progenitors share phenotypic, functional and gene expression profile similarities with lymphatics. J Cell Mol Med 2008.
20. Shantsila E, Watson T, Tse HF, Lip GY: New insights on endothelial progenitor cell subpopulations and their angiogenic properties. J Am Coll Cardiol 2008; 51(6):669-71.
21. Heissig B, Hattori K, Dias S, et al.: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002;109(5): 625-37.
22. Rafii S, Meeus S, Dias S, et al.: Contribution of marrow-derived progenitors to vascular and cardiac regeneration. Semin Cell Dev Biol 2002; 13(1): 61-7.
23. Aicher A, Heeschen C, Mildner-Rihm C, et al.: Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 2003; 9(11):1370-6.
24. Brem H, Tomic-Canic M: Cellular and molecular basis of wound healing in diabetes. J Clin Invest 2007; 117(5): 1219-22.
25. Kucia M, Jankowski K, Reca R, et al.: CXCR4-SDF-1 signalling, locomotion,chemotaxis and adhesion. J Mol Histol 2004; 35(3): 233-45.
26. Heeschen C, Aicher A, Lehmann R, et al.: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102(4): 1340-6.
27. Ishizawa K, Kubo H, Yamada M, et al.: Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett 2004;556(1-3): 249-52.
28. Tamarat R, Silvestre JS, Le Ricousse-Roussanne S, et al.: Impairment in ischemia-induced neovascularization in diabetes: bone marrow mononuclear cell dysfunction and therapeutic potential of placenta growth factor treatment. Am J Pathol 2004; 164(2): 457-66.
29. Darland DC, D'Amore PA: Blood vessel maturation: vascular development comes of age. J Clin Invest 1999; 103(2): 157-8.
30. Melero-Martin JM, De Obaldia ME, Kang SY, et al.: Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 2008; 103(2): 194-202.
31. Kocher AA, Schuster MD, Szabolcs MJ, et al.: Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7(4):430-6.
32. Rafii S, Lyden D: Cancer. A few to flip the angiogenic switch. Science 2008;319(5860): 163-4.
33. Moreno PR, Purushothaman KR, Fuster V, et al.: Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 2004; 110(14): 2032-8.
34. Tepper OM, Galiano RD, Capla JM, et al.: Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002; 106(22): 2781-6.
35. Landmesser U, Drexler H: The clinical significance of endothelial dysfunction. Curr Opin Cardiol 2005; 20(6): 547-51.
36. Vagnucci AH, Jr., Li WW: Alzheimer's disease and angiogenesis. Lancet 2003;361(9357): 605-8.
37. Iwaguro H, Yamaguchi J, Kalka C, et al.: Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation 2002;105(6): 732-8.
38. Hiasa K, Ishibashi M, Ohtani K, et al.: Gene transfer of stromal cell-derived factor-1 alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004; 109(20): 2454-61.
39. Llevadot J, Murasawa S, Kureishi Y, et al.: HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Glin Invest 2001;108(3): 399-405.
40. Kong D, Melo LG, Mangi AA, et al.: Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation 2004;109(14): 1769-75.
41. Follenzi A, Benten D, Novikoff P, Faulkner L, Raut S, Gupta S: Transplanted endothelial cells repopulate the liver endothelium and correct the phenotype of hemophilia A mice. J Clin Invest 2008; 118(3): 935-45.
42. Qiu HY, Fujimori Y, Nishioka K, et al.: Postnatal neovascularization by endothelial progenitor cells immortalized with the simian virus 40T antigen gene. Int J Oncol 2006; 28(4): 815-21.
43. Kaushal S, Amiel GE, Guleserian KJ, et al.: Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 2001; 7(9):1035-40.
44. Dome B, Timar J, Dobos J, et al.: Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. Cancer Res 2006; 66(14): 7341-7.
45. Schmidt-Lucke C, Rossig L, Fichtlscherer S, et al.: Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111(22):2981-7.
46. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA: Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 2004; 56(4):549-80.
47. Kawamoto A, Asahara T, Losordo DW: Transplantation of endothelial progenitor cells for therapeutic neovascularization. Cardiovasc Radiat Med 2002; 3(3-4): 221-5.
48. Zohlnhofer D, Kastrati A, Schomig A: Stem cell mobilization by granulocyte-colony-stimulating factor in acute myocardial infarction: lessons from the REVIVAL-2 trial. Nat Clin Pract Cardiovasc Med 2007; 4 Suppl 1: S106-9.
49. Takahashi M, Nakamura T, Toba T, Kajiwara N, Kato H, Shimizu Y:Transplantation of endothelial progenitor cells into the lung to alleviate pulmonary hypertension in dogs. Tissue Eng 2004; 10(5-6): 771-9.
50. Nagaya N, Kangawa K, Kanda M, et al.: Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells.Circulation 2003; 108(7): 889-95.
51. Hess D, Li L, Martin M, et al.: Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 2003; 21(7): 763-70.
52. Alison MR, Choong C, Lim S: Application of liver stem cells for cell therapy. Semin Cell Dev Biol 2007; 18(6): 819-26.
53. Yannaki E, Anagnostopoulos A, Kapetanos D, et al.: Lasting amelioration in the clinical course of decompensated alcoholic cirrhosis with boost infusions of mobilized peripheral blood stem cells. Exp Hematol 2006; 34(11): 1583-7.
54. Brittan M, Chance V, Elia G, et al.: A regenerative role for bone marrow following experimental colitis: contribution to neovasculogenesis and myofibroblasts.Gastroenterology 2005; 128(7): 1984-95.
55. Hill JM, Zalos G, Halcox JP, et al.: Circulating endothelial progenitor cells,vascular function, and cardiovascular risk. N Engl J Med 2003; 348(7): 593-600.
1. Belperio JA, Keane MP, Arenberg DA, et al.: CXC chemokines in angiogenesis. J Leukoc Biol 2000; 68(1): 1-8.
2. Strieter RM, Polverini PJ, Kunkel SL, et al.: The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem 1995; 270(45): 27348-57.
3. Salcedo R, Wasserman K, Young HA, et al.: Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1 alpha. Am J Pathol 1999; 154(4): 1125-35.
4. Hiasa K, Ishibashi M, Ohtani K, et al.: Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004; 109(20): 2454-61.
5. Hattori K, Heissig B, Tashiro K, et al.: Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 2001; 97(11): 3354-60.
6. Heissig B, Hattori K, Dias S, et al.: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002;109(5): 625-37.
7. Grunewald M, Avraham I, Dor Y, et al.: VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 2006; 124(1): 175-89.
8. Yamaguchi J, Kusano KF, Masuo O, et al.: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003; 107(9): 1322-8.
9. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al.: Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 2004;10(8): 858-64.
10. Cottier-Fox MH, Lapidot T, Petit I, et al.: Stem cell mobilization. Hematology Am Soc Hematol Educ Program 2003:419-37.
11. Heeschen C, Aicher A, Lehmann R, et al.: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102(4): 1340-6.
12. Todaro G, Green H: Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J. Cell Bio. 1963; 17:299-313.
13. Kim CH, Broxmeyer HE: Chemokines: signal lamps for trafficking of T and B cells for development and effector function. J Leukoc Biol 1999; 65(1): 6-15.
14. Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G: Chemokines and their receptors in the central nervous system. Front Neuroendocrinol 2001; 22(3): 147-84.
15. Horuk R: Chemokine receptors. Cytokine Growth Factor Rev 2001; 12(4):313-35.
16. Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC: The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997; 185(1): 111-20.
17. Tashiro K, Tada H, Heilker R, Shirozu M, Nakano T, Honjo T: Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science 1993; 261(5121): 600-3.
18. Nagasawa T, Kikutani H, Kishimoto T: Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci U S A 1994; 91(6): 2305-9.
19. Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA: A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 1996; 184(3): 1101-9.
20. Sadir R, Baleux F, Grosdidier A, Imberty A, Lortat-Jacob H: Characterization of the stromal cell-derived factor-lalpha-heparin complex. J Biol Chem 2001; 276(11):8288-96.
21. Netelenbos T, van den Born J, Kessler FL, et al.: Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells.Leukemia 2003; 17(1): 175-84.
22. Berson JF, Long D, Doranz BJ, Rucker J, Jirik FR, Doms RW: A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains. J Virol 1996; 70(9): 6288-95.
23. Hashimoto Y, Ohashi R, Kurosawa Y, et al.: Pharmacologic profile of TA-606, a novel angiotensin II-receptor antagonist in the rat. J Cardiovasc Pharmacol 1998;31(4): 568-75.
24. Lapham CK, Zaitseva MB, Lee S, Romanstseva T, Golding H: Fusion of monocytes and macrophages with HIV-1 correlates with biochemical properties of CXCR4 and CCR5. Nat Med 1999; 5(3): 303-8.
25. Shirozu M, Nakano T, Inazawa J, et al.: Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics 1995; 28(3):495-500.
26. Fuchs E, Tumbar T, Guasch G: Socializing with the neighbors: stem cells and their niche. Cell 2004; 116(6): 769-78.
27. Wright DE, Bowman EP, Wagers AJ, Butcher EC, Weissman IL: Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. J Exp Med 2002;195(9): 1145-54.
28. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998; 393(6685): 595-9.
29. Bajetto A, Barbieri F, Dorcaratto A, et al.: Expression of CXC chemokine receptors 1-5 and their ligands in human glioma tissues: role of CXCR4 and SDF1 in glioma cell proliferation and migration. Neurochem Int 2006; 49(5): 423-32.
30. Simmons G, Reeves JD, Hibbitts S, et al.: Co-receptor use by HIV and inhibition of HIV infection by chemokine receptor ligands. Immunol Rev 2000; 177: 112-26.
31. Orlic D, Kajstura J, Chimenti S, et al.: Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410(6829): 701-5.
32. Tateishi-Yuyama E, Matsubara H, Murohara T, et al.: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360(9331): 427-35.
33. Peled A, Kollet O, Ponomaryov T, et al.: The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 2000;95(11): 3289-96.
34. Schober A, Knarren S, Lietz M, Lin EA, Weber C: Crucial role of stromal cell-derived factor-1 alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation 2003; 108(20): 2491-7.
35. Schioppa T, Uranchimeg B, Saccani A, et al.: Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 2003; 198(9): 1391-402.
36. Zernecke A, Schober A, Bot I, et al.: SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res 2005; 96(7): 784-91.
37. Massberg S, Konrad I, Schurzinger K, et al.: Platelets secrete stromal cell-derived factor lalpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.J Exp Med 2006;203(5):1221-33.
38.Jin DK,Shido K,Kopp HG,et al.:Cytokine-mediated deployment of SDF-1induces revascularization through recruitment of CXCR4+ hemangiocytes.Nat Med 2006;12(5):557-67.
1. Asahara T, Murohara T, Sullivan A, et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275(5302): 964-7.
2. Hristov M, Erl W, Weber PC: Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol 2003; 23(7): 1185-9.
3. Murohara T, Ikeda H, Duan J, et al.: Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest 2000; 105(11):1527-36.
4. Kamihata H, Matsubara H, Nishiue T, et al.: Improvement of collateral perfiision and regional function by implantation of peripheral blood mononuclear cells into ischemic hibernating myocardium. Arterioscler Thromb Vasc Biol 2002; 22(11):1804-10.
5. Shintani S, Murohara T, Ikeda H, et al.: Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation 2001;103(6): 897-903.
6. Masuda H, Asahara T: Post-natal endothelial progenitor cells for neovascularization in tissue regeneration. Cardiovasc Res 2003; 58(2): 390-8.
7. Asahara T, Masuda H, Takahashi T, et al.: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85(3): 221-8.
8. Lee SH, Wolf PL, Escudero R, et al.: Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N Engl J Med 2000; 342(9): 626-33.
9. Pillarisetti K, Gupta SK: Cloning and relative expression analysis of rat stromal cell derived factor-1 (SDF-1)1: SDF-1 alpha mRNA is selectively induced in rat model of myocardial infarction. Inflammation 2001; 25(5): 293-300.
10. Shintani S, Murohara T, Ikeda H, et al.: Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 2001; 103(23): 2776-9.
11. Takahashi T, Kalka C, Masuda H, et al.: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5(4): 434-8.
12. Kocher AA, Schuster MD, Szabolcs MJ, et al.: Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7(4): 430-6.
13. Minamino K, Adachi Y, Okigaki M, et al.: Macrophage colony-stimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization. Stem Cells 2005; 23(3): 347-54.
14. Bahlmann FH, De Groot K, Spandau JM, et al.: Erythropoietin regulates endothelial progenitor cells. Blood 2004; 103(3): 921-6.
15. Moore MA, Hattori K, Heissig B, et al.: Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1. Ann N Y Acad Sci 2001; 938: 36-45; discussion 45-7.
16. van Royen N, Schirmer SH, Atasever B, et al.: START Trial: a pilot study on STimulation of ARTeriogenesis using subcutaneous application of granulocyte-macrophage colony-stimulating factor as a new treatment for peripheral vascular disease. Circulation 2005; 112(7): 1040-6.
17. Honold J, Lehmann R, Heeschen C, et al.: Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol 2006; 26(10):2238-43.
18. Maiese K, Li F, Chong ZZ: New avenues of exploration for erythropoietin. Jama 2005; 293(1): 90-5.
19. Prass K, Scharff A, Ruscher K, et al.: Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 2003; 34(8): 1981-6.
20. Wright GL, Hanlon P, Amin K, Steenbergen C, Murphy E, Arcasoy MO:Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury. Faseb J 2004; 18(9): 1031-3.
21. Hanlon PR, Fu P, Wright GL, Steenbergen C, Arcasoy MO, Murphy E:Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: role of protein kinase C and phosphatidylinositol 3-kinase signaling. Faseb J 2005; 19(10): 1323-5.
22. Heeschen C, Aicher A, Lehmann R, et al.: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102(4): 1340-6.
23. Westenbrink BD, Lipsic E, van der Meer P, et al.: Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J 2007; 28(16): 2018-27.
24. Lipsic E, van der Meer P, Voors AA, et al.: A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther 2006; 20(2):135-41.
25. Grunewald M, Avraham I, Dor Y, et al.: VEGF-induced adult neovascularization:recruitment, retention, and role of accessory cells. Cell 2006; 124(1): 175-89.
26. Yamaguchi J, Kusano KF, Masuo O, et al.: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003; 107(9): 1322-8.
27. Hiasa K, Ishibashi M, Ohtani K, et al.: Gene transfer of stromal cell-derived factor-1 alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004; 109(20): 2454-61.
28. Woo YJ, Grand TJ, Berry MF, et al.: Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. J Thorac Cardiovasc Surg 2005; 130(2): 321-9.
29. Atluri P, Liao GP, Panlilio CM, et al.: Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Ann Thorac Surg 2006;81(5): 1728-36.
30. Misao Y, Takemura G, Arai M, et al.: Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-CSF.Cardiovasc Res 2006; 71(3): 455-65.
3
1. Niiyama H, Kai H, Yamamoto T, et al.: Roles of endogenous monocyte chemoattractant protein-1 in ischemia-induced neovascularization. J Am Coll Cardiol 2004; 44(3): 661-6.
32. Dokun AO, Keum S, Hazarika S, et al.: A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical hindlimb ischemia. Circulation 2008; 117(9): 1207-15.
33. Kuhlmann CR, Schaefer CA, Reinhold L, Tillmanns H, Erdogan A: Signalling mechanisms of SDF-induced endothelial cell proliferation and migration. Biochem Biophys Res Commun 2005; 335(4): 1107-14.
34. Guo Y, Hangoc G, Bian H, Pelus LM, Broxmeyer HE: SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells. Stem Cells 2005; 23(9): 1324-32.
35. Brunner S, Winogradow J, Huber BC, et al.: Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. Faseb J 2009; 23(2): 351-61.
36. Brunner S, Huber BC, Fischer R, et al.: G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells. Exp Hematol 2008; 36(6): 695-702.
37. Askari AT, Unzek S, Popovic ZB, et al.: Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 2003;362(9385): 697-703.
38. Tateishi-Yuyama E, Matsubara H, Murohara T, et al.: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360(9331): 427-35.
39. Kawamoto A, Asahara T, Losordo DW: Transplantation of endothelial progenitor cells for therapeutic neovascularization. Cardiovasc Radiat Med 2002; 3(3-4): 221-5.
40. Landmesser U, Drexler H: The clinical significance of endothelial dysfunction.Curr Opin Cardiol 2005; 20(6): 547-51.
41. Uchida E, Morimoto K, Kawasaki N, Izaki Y, Abdu Said A, Hayakawa T: Effect of active oxygen radicals on protein and carbohydrate moieties of recombinant human erythropoietin. Free Radic Res 1997; 27(3): 311-23.
42. Chong ZZ, Kang JQ, Maiese K: Hematopoietic factor erythropoietin fosters neuroprotection through novel signal transduction cascades. J Cereb Blood Flow Metab 2002; 22(5): 503-14.
43. Chong ZZ, Kang JQ, Maiese K: Angiogenesis and plasticity: role of erythropoietin in vascular systems. J Hematother Stem Cell Res 2002; 11(6): 863-71.
44. Gene S, Koroglu TF, Genc K: Erythropoietin as a novel neuroprotectant. Restor Neurol Neurosci 2004; 22(2): 105-19.
45. Anagnostou A, Liu Z, Steiner M, et al.: Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci U S A 1994; 91(9): 3974-8.
46. Ribatti D, Presta M, Vacca A, et al.: Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 1999; 93(8): 2627-36.
47. Hewitson KS, McNeill LA, Schofield CJ: Modulating the hypoxia-inducible factor signaling pathway: applications from cardiovascular disease to cancer. Curr Pharm Des 2004; 10(8): 821-33.
48. Sakamaki K: Regulation of endothelial cell death and its role in angiogenesis and vascular regression. Curr Neurovasc Res 2004; 1(4): 305-15.
49. Maiese K, Chong ZZ: Insights into oxidative stress and potential novel therapeutic targets for Alzheimer disease. Restor Neurol Neurosci 2004; 22(2): 87-104.
50. Kawakami M, Sekiguchi M, Sato K, Kozaki S, Takahashi M: Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia. J Biol Chem 2001; 276(42): 39469-75.
51. Chong ZZ, Li F, Maiese K: Activating Akt and the brain's resources to drive cellular survival and prevent inflammatory injury. Histol Histopathol 2005; 20(1):299-315.
52. Chong ZZ, Kang JQ, Maiese K: Erythropoietin is a novel vascular protectant through activation of Aktl and mitochondrial modulation of cysteine proteases. Circulation 2002; 106(23): 2973-9.
53. Chong ZZ, Kang JQ, Maiese K: Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. J Cereb Blood Flow Metab 2003; 23(3): 320-30.
54. Somervaille TC, Linch DC, Khwaja A: Growth factor withdrawal from primary human erythroid progenitors induces apoptosis through a pathway involving glycogen synthase kinase-3 and Bax. Blood 2001; 98(5): 1374-81.
55. George J, Goldstein E, Abashidze A, et al.: Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. Cardiovasc Res 2005; 68(2): 299-306.
56. Carlini RG, Reyes AA, Rothstein M: Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int 1995; 47(3): 740-5.
57. Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck KH: Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 2002; 64(2): 326-33.
58. Nakano M, Satoh K, Fukumoto Y, et al.: Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice. Circ Res 2007; 100(5): 662-9.
59. Erslev AJ, Caro J: Erythropoietin: from mountain top to bedside. Adv Exp Med Biol 1989; 271:1-7.
60. Hayashi T, Suzuki A, Shoji T, et al.: Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure. Am J Kidney Dis 2000; 35(2): 250-6.
61. Jelkmann W: Biology of erythropoietin. Clin Investig 1994; 72(6 Suppl): S3-10.
62. Hebert PC, Wells G, Blajchman MA, et al.: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340(6): 409-17.
63. Rao SV, Stamler JS: Erythropoietin, anemia, and orthostatic hypotension: the evidence mounts. Clin Auton Res 2002; 12(3): 141-3.
64. Grimm C, Wenzel A, Groszer M, et al.: HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med 2002; 8(7):718-24.
65. Digicaylioglu M, Lipton SA: Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 2001; 412(6847):641-7.
66. Ihle JN: Cytokine receptor signalling. Nature 1995; 377(6550): 591-4.
67. Wojchowski DM, Gregory RC, Miller CP, Pandit AK, Pircher TJ: Signal transduction in the erythropoietin receptor system. Exp Cell Res 1999; 253(1):143-56.
68. Palmer LA, Gaston B, Johns RA: Normoxic stabilization of hypoxia-inducible factor-1 expression and activity: redox-dependent effect of nitrogen oxides. Mol Pharmacol 2000; 58(6): 1197-203.
69. Maiese K, Li F, Chong ZZ: Erythropoietin in the brain: can the promise to protect be fulfilled? Trends Pharmacol Sci 2004; 25(11): 577-83.
70. Jelkmann W, Wagner K: Beneficial and ominous aspects of the pleiotropic action of erythropoietin. Ann Hematol 2004; 83(11): 673-86.
71. van der Meer P, Voors AA, Lipsic E, Smilde TD, van Gilst WH, van Veldhuisen DJ: Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol 2004; 44(1): 63-7.
72. Henry DH, Bowers P, Romano MT, Provenzano R: Epoetin alfa. Clinical evolution of a pleiotropic cytokine. Arch Intern Med 2004; 164(3): 262-76.
73. Ajmani RS, Metter EJ, Jaykumar R, et al.: Hemodynamic changes during aging associated with cerebral blood flow and impaired cognitive function. Neurobiol Aging 2000; 21(2): 257-69.
74. Moulton KS, Vakili K, Zurakowski D, et al.: Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci U S A 2003; 100(8): 4736-41.
75. Bennett CL, Luminari S, Nissenson AR, et al.: Pure red-cell aplasia and epoetin therapy. N Engl J Med 2004; 351(14): 1403-8.
76. Verdier F, Walrafen P, Hubert N, et al.: Proteasomes regulate the duration of erythropoietin receptor activation by controlling down-regulation of cell surface receptors. J Biol Chem 2000; 275(24): 18375-81.
77. Moon C, Krawczyk M, Ahn D, et al.: Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A 2003; 100(20): 11612-7.
78. Lipsic E, Westenbrink BD, van der Meer P, et al.: Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit. Eur J Heart Fail 2008; 10(1): 22-9.
79. Leist M, Ghezzi P, Grasso G, et al.: Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 2004; 305(5681): 239-42.
80. Moon C, Krawczyk M, Paik D, et al.: Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties. J Pharmacol Exp Ther 2006; 316(3): 999-1005.
81. Fiordaliso F, Chimenti S, Staszewsky L, et al.: A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury. Proc Natl Acad Sci U S A 2005; 102(6): 2046-51.
1.Criqui MH,Fronek A,Barrett-Connor E,Klauber MR,Gabriel S,Goodman D:The prevalence of peripheral arterial disease in a defined population.Circulation 1985;71(3):510-5.
2.Murabito JM,D'Agostino RB,Silbershatz H,Wilson WF:Intermittent claudication.A risk profile from The Framingham Heart Study.Circulation 1997;96(1):44-9.
3.Dormandy J,Heeck L,Vig S:The fate of patients with critical leg ischemia.Semin Vasc Surg 1999;12(2):142-7.
4.Norgren L,Hiatt WR,Dormandy JA,Nehler MR,Harris KA,Fowkes FG:Inter-Society Consensus for the Management of Peripheral Arterial Disease(TASC Ⅱ). J Vasc Surg 2007; 45 Suppl S: S5-67.
5. Adam DJ, Beard JD, Cleveland T, et al.: Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet 2005;366(9501): 1925-34.
6. Baumgartner I, Schainfeld R, Graziani L: Management of peripheral vascular disease. Annu Rev Med 2005; 56:249-72.
7. Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nat Med 2000; 6(4):389-95.
8. Saniabadi AR, Marney Y, Belch JJ, et al.: Further evidence that the residual vWf:Ag in porcine FVIILC induces human platelet aggregation. Haemostasis 1990;20(5): 289-95.
9. Schaper W, Scholz D: Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol 2003; 23(7): 1143-51.
10. Heil M, Schaper W: Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res 2004; 95(5): 449-58.
11. Heil M, Eitenmuller I, Schmitz-Rixen T, Schaper W: Arteriogenesis versus angiogenesis: similarities and differences. J Cell Mol Med 2006; 10(1): 45-55.
12. Babiak A, Schumm AM, Wangler C, et ah: Coordinated activation of VEGFR-1 and VEGFR-2 is a potent arteriogenic stimulus leading to enhancement of regional perfusion. Cardiovasc Res 2004; 61(4): 789-95.
13. Panchal VR, Rehman J, Nguyen AT, et al.: Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease. J Am Coll Cardiol 2004; 43(8): 1383-7.
14. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 1(1): 27-31.
15. Wang GL, Semenza GL: General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A 1993; 90(9): 4304-8.
16. Kelly BD, Hackett SF, Hirota K, et al.: Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res 2003; 93(11):1074-81.
17. Rissanen TT, Korpisalo P, Markkanen JE, et al.: Blood flow remodels growing vasculature during vascular endothelial growth factor gene therapy and determines between capillary arterialization and sprouting angiogenesis. Circulation 2005; 112(25): 3937-46.
18. Asahara T, Masuda H, Takahashi T, et al.: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85(3): 221-8.
19. Isner JM, Asahara T: Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest 1999; 103(9): 1231-6.
20. Takeshita S, Zheng LP, Brogi E, et al.: Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 1994; 93(2): 662-70.
21. Losordo DW, Dimmeler S: Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part I: angiogenic cytokines. Circulation 2004; 109(21): 2487-91.
22. Tio RA, Wijpkema JS, Tan ES, et al.: Functional characteristics of coronary vasomotor function following intramyocardial gene therapy with naked DNA encoding for vascular endothelial growth factorl65. Endothelium 2005; 12(3): 103-6.
23. Bahlmann FH, De Groot K, Spandau JM, et al.: Erythropoietin regulates endothelial progenitor cells. Blood 2004; 103(3): 921-6.
24. Kalka C, Masuda H, Takahashi T, et al.: Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects.Circ Res 2000; 86(12): 1198-202.
25. Henry TD: Therapeutic angiogenesis. Bmj 1999; 318(7197): 1536-9.
26. Klagsbrun M, D'Amore PA: Vascular endothelial growth factor and its receptors.Cytokine Growth Factor Rev 1996; 7(3): 259-70.
27. Gitay-Goren H, Cohen T, Tessler S, et al.: Selective binding of VEGF121 to one of the three vascular endothelial growth factor receptors of vascular endothelial cells.J Biol Chem 1996; 271(10): 5519-23.
28. Shalaby F, Rossant J, Yamaguchi TP, et al.: Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995; 376(6535): 62-6.
29. Powers CJ, McLeskey SW, Wellstein A: Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 2000; 7(3): 165-97.
30. Couchman JR: Syndecans: proteoglycan regulators of cell-surface microdomains? Nat Rev Mol Cell Biol 2003; 4(12): 926-37.
31. Bauters C, Six I, Meurice T, Van Belle E: Growth factors and endothelial dysfunction. Drugs 1999; 59 Spec No: 11-5.
32. Detillieux KA, Sheikh F, Kardami E, Cattini PA: Biological activities of fibroblast growth factor-2 in the adult myocardium. Cardiovasc Res 2003; 57(1): 8-19.
33. Asahara T, Bauters C, Zheng LP, et al.: Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation 1995; 92(9 Suppl): 11365-71.
34. Ferrara N, Houck K, Jakeman L, Leung DW: Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992; 13(1):18-32.
35. Unger EF, Goncalves L, Epstein SE, et al.: Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris. Am J Cardiol 2000; 85(12): 1414-9.
36. Lazarous DF, Unger EF, Epstein SE, et al.: Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial. J Am Coll Cardiol 2000; 36(4): 1239-44.
37. Cooper LT, Jr., Hiatt WR, Creager MA, et al.: Proteinuria in a placebo-controlled study of basic fibroblast growth factor for intermittent claudication. Vasc Med 2001;6(4): 235-9.
38. Simons M, Bonow RO, Chronos NA, et al.: Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary. Circulation 2000; 102(11):E73-86.
39. Wolff JA, Malone RW, Williams P, et al.: Direct gene transfer into mouse muscle in vivo. Science 1990; 247(4949 Pt 1): 1465-8.
40. Mulligan RC: The basic science of gene therapy. Science 1993; 260(5110):926-32.
41. Gao X, Huang L: Cationic liposome-mediated gene transfer. Gene Ther 1995;2(10): 710-22.
42. Yla-Herttuala S, Alitalo K: Gene transfer as a tool to induce therapeutic vascular growth. Nat Med 2003; 9(6): 694-701.
43. Dor Y, Djonov V, Abramovitch R, et al.: Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. Embo J 2002;21(8): 1939-47.
44. Baumgartner I, Pieczek A, Manor O, et al.: Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998; 97(12): 1114-23.
45. Baumgartner I, Rauh G, Pieczek A, et al.: Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor. Ann Intern Med 2000; 132(11): 880-4.
46. Isner JM, Baumgartner I, Rauh G, et al.: Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg 1998; 28(6): 964-73; discussion 73-5.
47. Losordo DW, Vale PR, Symes JF, et al.: Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 1998; 98(25): 2800-4.
48. Shyu KG, Chang H, Wang BW, Kuan P: Intramuscular vascular endothelial growth factor gene therapy in patients with chronic critical leg ischemia. Am J Med 2003; 114(2): 85-92.
49. Comerota AJ, Throm RC, Miller KA, et al.: Naked plasmid DNA encoding fibroblast growth factor type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: preliminary results of a phase I trial. J Vase Surg 2002; 35(5):930-6.
50. Nikol S, Baumgartner I, Van Belle E, et al.: Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther 2008; 16(5): 972-8.
51. Makinen K, Manninen H, Hedman M, et al.: Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study. Mol Ther 2002; 6(1):127-33.
52. Rajagopalan S, Mohler ER, 3rd, Lederman RJ, et al.: Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication.Circulation 2003; 108(16): 1933-8.
53. Kalka C, Baumgartner I: Gene and stem cell therapy in peripheral arterial occlusive disease. Vasc Med 2008; 13(2): 157-72.
54. Kusumanto YH, van Weel V, Mulder NH, et al.: Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. Hum Gene Ther 2006; 17(6): 683-91.
55. Horowitz JR, Rivard A, van der Zee R, et al.: Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension.Evidence for a maintenance role in quiescent adult endothelium. Arterioscler Thromb Vasc Biol 1997; 17(11): 2793-800.
56. Schwarz ER, Speakman MT, Patterson M, et al.: Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat~angiogenesis and angioma formation. J Am Coll Cardiol 2000; 35(5): 1323-30.
57. Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM: VEGF gene delivery to muscle: potential role for vasculogenesis in adults. Mol Cell 1998; 2(5): 549-58.
58. Tio RA, Tkebuchava T, Scheuermann TH, et al.: Intramyocardial gene therapy with naked DNA encoding vascular endothelial growth factor improves collateral flow to ischemic myocardium. Hum Gene Ther 1999; 10(18): 2953-60.
59. Vale PR, Isner JM, Rosenfield K: Therapeutic angiogenesis in critical limb and myocardial ischemia. J Interv Cardiol 2001; 14(5): 511-28.
60. Isner JM, Vale PR, Symes JF, Losordo DW: Assessment of risks associated with cardiovascular gene therapy in human subjects. Circ Res 2001; 89(5): 389-400.
61. Inoue M, Itoh H, Ueda M, et al.: Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis. Circulation 1998; 98(20): 2108-16.
62. Isner JM: Cancer and atherosclerosis: the broad mandate of angiogenesis.Circulation 1999; 99(13): 1653-5.
63. Odorico JS, Kaufman DS, Thomson JA: Multilineage differentiation from human embryonic stem cell lines. Stem Cells 2001; 19(3): 193-204.
64. Teramoto K, Hara Y, Kumashiro Y, et al.: Teratoma formation and hepatocyte differentiation in mouse liver transplanted with mouse embryonic stem cell-derived embryoid bodies. Transplant Proc 2005; 37(1): 285-6.
65. Asahara T, Murohara T, Sullivan A, et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275(5302): 964-7.
66. Lin Y, Weisdorf DJ, Solovey A, Hebbel RP: Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105(1): 71-7.
67. Rehman J, Li J, Orschell CM, March KL: Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.Circulation 2003; 107(8): 1164-9.
68. Heissig B, Hattori K, Dias S, et al.: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002;109(5): 625-37.
69. Aicher A, Heeschen C, Mildner-Rihm C, et al.: Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 2003; 9(11):1370-6.
70. Kalka C, Masuda H, Takahashi T, et al.: Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 2000; 97(7): 3422-7.
71. Murayama T, Tepper OM, Silver M, et al.: Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 2002; 30(8): 967-72.
72. Crosby JR, Kaminski WE, Schatteman G, et al.: Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ Res 2000;87(9): 728-30.
73. Kawamoto A, Iwasaki H, Kusano K, et al.: CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 2006; 114(20): 2163-9.
74. Jackson KA, Majka SM, Wang H, et al.: Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001; 107(11): 1395-402.
75. Assmus B, Schachinger V, Teupe C, et al.: Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI).Circulation 2002; 106(24): 3009-17.
76. Assmus B, Honold J, Schachinger V, et al.: Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006; 355(12): 1222-32.
77. Lunde K, Solheim S, Aakhus S, et al.: Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355(12):1199-209.
78. Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S: Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction.Eur Heart J 2007; 28(6): 766-72.
79. Tateishi-Yuyama E, Matsubara H, Murohara T, et al.: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360(9331): 427-35.
80. Higashi Y, Kimura M, Hara K, et al.: Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation 2004; 109(10): 1215-8.
81. Ross R: Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340(2):115-26.
82. Seiler C, Pohl T, Wustmann K, et al.: Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study. Circulation 2001;104(17): 2012-7.
83. Heeschen C, Lehmann R, Honold J, et al.: Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 2004; 109(13): 1615-22.
84. Griese DP, Achatz S, Batzlsperger CA, et al.: Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells. Cardiovasc Res 2003; 58(2): 469-77.
85. Hu Y, Davison F, Zhang Z, Xu Q: Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells.Circulation 2003; 108(25): 3122-7.
86. George J, Afek A, Abashidze A, et al.: Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2005; 25(12): 2636-41.
87. Silvestre JS, Gojova A, Brun V, et al.: Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation 2003; 108(23):2839-42.
88. Sata M: Circulating vascular progenitor cells contribute to vascular repair, remodeling, and lesion formation. Trends Cardiovasc Med 2003; 13(6): 249-53.
89. Werner N, Kosiol S, Schiegl T, et al.: Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353(10): 999-1007.
90. Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW: Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.Circulation 2004; 109(25): 3154-7.
91. Spring H, Schuler T, Arnold B, Hammerling GJ, Ganss R: Chemokines direct endothelial progenitors into tumor neovessels. Proc Natl Acad Sci U S A 2005;102(50): 18111-6.
92. Davidoff AM, Ng CY, Brown P, et al.: Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin Cancer Res 2001; 7(9): 2870-9.
93. Schuch G, Heymach JV, Nomi M, et al.: Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells. Cancer Res 2003; 63(23): 8345-50.