激活Notch信号的骨髓间充质干细胞心肌移植治疗心梗模型鼠的实验研究
|
摘要
背景由于再生能力有限,心肌梗死后存活的心肌细胞不能修复梗死区,局部心肌组织缺血、缺氧,心肌细胞大量坏死,纤维组织增生,疤痕组织形成,心室重塑,导致心功能下降。BMMSCs移植可以增加梗死区肌细胞数量,改善心功能,血管内皮细胞生长因子在心肌梗死急性期的表达增加,促进梗死区新生血管形成。Notch信号是细胞与细胞之间直接作用的主要信号通路之一,并对多细胞生物中细胞命运的决定起关键作用。ICN是Notch的活性形式,通过载体介导将ICN转染细胞就可以在没有配体存在的情况下激活Notch信号,为研究Notch信号的生物功能提供了方便。目的本研究旨在观察激活Notch信号的BMMSCs移植到梗死心肌后毛细血管密度及心功能改善情况。目前转染ICN基因的BMMSCs移植对心肌梗死后心脏重构的影响还不是很清楚。本研究观察逆转录病毒介导的ICN基因转染BMMSCs后ICN基因的表达,观察逆转录病毒介导的ICN基因转染的诱导BMMSCs植入梗死心肌后对心脏重构的影响,BMMSCs能否在梗死区存活、向心肌细胞方向分化,以及梗死后心功能和心肌灌注是否得到改善,并探讨其机理,为BMMSCs转染基因治疗缺血性心脏病提供实验依据。方法1.用密度梯度离心法分离大鼠BMMSCs,体外培养、5-氮胞苷诱导,用相差显微镜、电子显微镜、免疫细胞化学方法和流式细胞仪等对诱导细胞进行鉴定。2.通过逆转录病毒介导的基因转移方法转染ICN激活BMMSCs的Notch信号通路,用RT-PCR法测定转染后ICN在BMMSCs的表达。3.结扎大鼠冠状动脉前降支建立大鼠急性心肌梗死模型,超声心动图观察心肌梗死前、后心功能变化,并观察结扎前、后心电图变化。4.选取的80只近交系Wister大鼠随机分为假手术对照组10只(A组)、建立急性心肌梗死(AMI)模型组70只,成功制成心肌梗死模型并成活60只,建立模型后随机分为MI模型组(B组)、培养液移植组(C组)、激活Noth信号的BMMSCs移植组(D组)、BMSCs移植组(E组),每组15只。移植前2小时,培养细胞用DAPI标记。结扎冠状动脉后2周,均经前次手术经路开胸,分别向梗死区注射容积为0.1ml的DMEM培养液、BMSCs、激活Noth信号的BMMSCs,假手术组则在左前降支周围心前壁多点注射0.1ml生理盐水。分别在造模后1天、28天行心脏超声心动图检查比较心功能变化。移植后28天处死大鼠,心脏标本测量比较形态变化;心脏标本切片行荧光显微镜检查定位移植细胞存活情况;免疫组化检查Ⅷ因子抗体表达计数毛细血管密度,VEGF表达情况,检查结蛋白,肌钙蛋白I等抗体表达鉴定移植细胞分化,并比较胶原蛋白、基质金属蛋白酶表达变化。结果1.成功分离出大鼠BMMSCs,流式细胞仪检查提示培养细胞表达CD29,Flk-1,CD117等抗体。2.成功地通过逆转录病毒介导的基因转移方法将ICN转染BMMSCs以激活了BMMSCs的Notch信号通路,用RT-PCR法测定转染后ICN在BMMSCs的表达。3.成功制备大鼠急性心肌梗死模型。阻断冠状动脉血流后,心电图示肢体导联ST段压低,心率加快,出现室性早搏;术后ST段弓背抬高,术后8小时ST段下降,QRS波增宽,出现病理性Q波;术后24小时彩色多普勒超声检查见左心室心腔扩大,前壁局部心肌运动障碍,左心室射血分数术后(39.67±2.33)%较术前(62.35±3.49)%及假手术组(60.52±4.75)%明显下降(p＜0.01);术后4周的大鼠心脏标本HE染色可见左心室前壁局部结缔组织增生,心肌细胞明显减少,提示心肌梗死区形成。4.细胞移植组心脏标本HE染色示左心室前壁有结缔组织增生,形状不规则,其中有成纤维细胞,有异源性细胞;心梗模型组、DMEM培养液移植组标本HE染色可见疤痕组织,未发现异常细胞。假手术组未发现疤痕组织和异常细胞。在细胞移植组心脏标本中发现标记的荧光细胞,在心梗模型组、DMEM培养液移植组心脏标本中未发现标记细胞,在假手术组心脏标本中未发现标记细胞。移植细胞组结蛋白染色阳性,肌钙蛋白I染色阳性,提示移植的细胞向心肌样细胞分化趋势,并且激活Notch信号的BMMSCs移植组抗体阳性表达明显高于单纯BMMSCs移植组。心脏彩色多普勒超声检查发现细胞移植后4周,心肌局部运动功能障碍消失,心腔缩小,左心室射血分数升高。统计学分析表明,激活Notch信号的BMMSCs移植组大鼠心功能与BMMSCs移植、心梗模型组和DMEM培养液移植组相比,明显改善。与BMMSCs移植、心梗模型组和DMEM培养液移植相比,激活Notch信号的BMMSCs移植组大鼠心脏的心肌梗死范围明显减小,心室壁厚度明显增加,毛细血管密度明显增加,VEGF蛋白表达明显增多,I型胶原抗体、基质金属蛋白酶-1抗体表达明显减轻。结论激活Notch信号的BMMSCs移植及单纯BMMSCs移植细胞可在心肌内存活,并分化为心肌样性细胞,高效表达VEGF蛋白,梗死区新生血管形成增加,心脏胶原、基质金属蛋白酶合成降低,心脏重构减轻,心功能明显改善。激活Notch信号的BMMSCs移植治疗心肌梗死是有效的。
Background Viablec ardiomyocytes after myocardial infarction(MI) are unable to repair the necrotic myocardium due to their limited capability of regeneration.Coronary artery occlusion caused myocardial infarction,followed by cardiomyocytes death,fibroplasia,scar formation and cardiac remodeling due to ischemia.Heart function abruptly decreased.Transplantation of bone marrow mesenchymal stem cells (BMMSCs) increased the number of myogenic cells in myocardial infarction tissue and improved heart function.Level of serum vascular endothelial growth factor(VEGF) increased at acute phase of myocardial infarction.It may enhance angiogenesis around myocardial infarction tissue.Notch signal is one of the main direct action signal path between cell and cell,and is key point to determine cell fate of organisma multicellularis.The Intracellular Domain of Notch(ICN) is activity style of Notch signal,Notch signal is activated without ligand through transfection of ICN by carrying agent mediated.It provide convenience to study and research for biological function of Notch signal.Purpose we designed the experiment to probe the efects of capillary density and heart function through BMMSCs transfected ICN gene on cardiac remodeling after myocardial infarction.At present,The influence of BMMSCs transfected ICN gene on cardiac remodeling after myocardial infarction on the heart reconstitution is not very clear.we designed the experiment to probe the influence of the heart reconstitution through BMMSCs transfected ICN gene on cardiac remodeling after myocardial infarction. ntroversial.In order to investigate whether the implantation of BMMSCs results in sustained engraftment and myogenic differentiation,improves the postinfarction left ventricular(LV) perfusion and cardiac function.This research would provide experimental data for the treatment of ischemic heart disease with BMMSCs transferred with gene.Methods 1. BMMSCs were isolated from inbred line Wister rat's tibia and fibula with density gradient centrifugation,cultured in vitro,and induced with 5-azacytidine.The phase-contrast microscope,electron microscope, immunohistochemistry stain,and flow cytometry were applied to identify the induced cells.2.Our lab had constructed BMMSCs with Notch signal is activated without ligand through transfection of ICN through retrovirus-mediated gene transfer.We detect the express of ICN in BMMSCs after ICN transfection through Retroviridase polymerase chain reaction(RT-PCR).3.Acute myocardial infarction model of rats was constructed by occlusion of left coronary anterior descending branch.Chang of heart function was compared between post MI and before MI by echocardiogragm and electrocardiogram.4.80 inbred line Wister rats was random divided sham operation control group(A group,10 rats) and construction acute myocardial infarctionsurvived(AMI) group(70 rats),60 rats survival from operation were randomly and equally assigned to myocardial infarctionsurvived group(B group,15 rats),culture fluid transplantation group(C group,1 5 rats),BMMSC s activaed Notch signal transplantation group(D group,15 rats) and BMMSCs transplantation group(E group,15 rats).Cultuerd cells were labeled with DAPI 2 hours before cel ls transplantation.2 weeks after ligation of left coronary anterior descending branch,0.1ml volume of induced BMMSCs transferred with ICN,induced BMMSCs without transfection of ICN,culture fluid,and physiological saline were injected into the area of myocardial infarction,respectively.Echocardiography examinations were performed to evaluate heart function at day 1,28 after operation,respectively.Rats were sacrificed 28 days after operation,heart samples were fixed with formalin for pathologic examination. Morphologic change of heart samples were assessed by gross examination.Transplanted cells were located by fluorescence microscopy examination.Capillary density,which was identified by expression ofⅧfactor antibody,was counted in hearts,Desmin and troponinⅠantibody stain were used to identified the difeerntiation of transplanted cells.Expression of collagen and MMPs in rat's hearts was evaluated as well.Results 1.BMMSCs of rats was successfully segregated.Flow cytometry showed that cultured cells were positive for anti-CD29 antibody,anti-Flk-1 antibody,and anti-CD117 antibody.All of which confirmed that the induced BMMSCs differentiated into the myogenic cells.2.successfully constructed BMMSCs with Notch signal is activated without ligand through transfection of ICN through retrovirus-mediated gene transfer.We detect the express of ICN in BMMSCs after ICN transfection through RT-PCR.
3.Myocardial infarction of rats was successfully constructed.ECG showed that ST segment was depressed and heart rates was faster when coronary artery was obstructed,ST segment was elevated and QRS complex was wider,and ST segment was depressed and Q wave appeared 8 hours later.Left ventricle was enlarged,local myocardial dyskinesis was found,and left ventricle Ejection Fraction(EF) decreased obviously by echocardiogram.Left ventricle EF of the operated rats(62.35±3.49)%, 24 hours after operation was lower than that of the rats before operation(39.67±2.33)%and sham operation rats(60.52±4.75)(p＜0.01).HE stain of heart samples collected 4 weeks after operation displayed local scar tissues devoid of cardiomyocytes,suggesting the formation of myocardial infarction.4.HE stain showed there was irregular scar tissues in anterior wall of left ventricle in cell D and E group,where allogenic cells(fluorescent cells) were found.Scar tissues but not allogenic cells were found in A group.Transplanted cells were positive for desmin and troponinⅠantibody.Echocardiogram demonstrated that local myocardial dyskinesis disappeared,volume of left ventricle got smaller,and left ventricle EF was elevated.Results of statistics analysis were as follows:heart function of rats in D group was beter than that of E group, B group,and C group.Infarcted areas and thickness of rats in D group were beter than that of E group,B group,and C group.Capillary density in D group was much more than that of others groups.Expression of type 1 collagen and MMP-1 in rats in induced D group was weaker than that of others groups.Conclunions Transplanted cells were alive in infarct myocardium and diferentiated into myogenic cells.Transplantation of BMMSCs transferred with ICN into myocardial infarction increased angiogenesis in infarct myocardium,decreased synthesis of collagen and matrix metalloproteinase,alleviated cardiac remodeling,and improved heart function.Transplantation of BMMSCs transferred with ICN was useful and safe for the treatment of myocardial infarction.
Background Viablec ardiomyocytes after myocardial infarction(MI) are unable to repair the necrotic myocardium due to their limited capability of regeneration.Coronary artery occlusion caused myocardial infarction,followed by cardiomyocytes death,fibroplasia,scar formation and cardiac remodeling due to ischemia.Heart function abruptly decreased.Transplantation of bone marrow mesenchymal stem cells (BMMSCs) increased the number of myogenic cells in myocardial infarction tissue and improved heart function.Level of serum vascular endothelial growth factor(VEGF) increased at acute phase of myocardial infarction.It may enhance angiogenesis around myocardial infarction tissue.Notch signal is one of the main direct action signal path between cell and cell,and is key point to determine cell fate of organisma multicellularis.The Intracellular Domain of Notch(ICN) is activity style of Notch signal,Notch signal is activated without ligand through transfection of ICN by carrying agent mediated.It provide convenience to study and research for biological function of Notch signal.Purpose we designed the experiment to probe the efects of capillary density and heart function through BMMSCs transfected ICN gene on cardiac remodeling after myocardial infarction.At present,The influence of BMMSCs transfected ICN gene on cardiac remodeling after myocardial infarction on the heart reconstitution is not very clear.we designed the experiment to probe the influence of the heart reconstitution through BMMSCs transfected ICN gene on cardiac remodeling after myocardial infarction. ntroversial.In order to investigate whether the implantation of BMMSCs results in sustained engraftment and myogenic differentiation,improves the postinfarction left ventricular(LV) perfusion and cardiac function.This research would provide experimental data for the treatment of ischemic heart disease with BMMSCs transferred with gene.Methods 1. BMMSCs were isolated from inbred line Wister rat's tibia and fibula with density gradient centrifugation,cultured in vitro,and induced with 5-azacytidine.The phase-contrast microscope,electron microscope, immunohistochemistry stain,and flow cytometry were applied to identify the induced cells.2.Our lab had constructed BMMSCs with Notch signal is activated without ligand through transfection of ICN through retrovirus-mediated gene transfer.We detect the express of ICN in BMMSCs after ICN transfection through Retroviridase polymerase chain reaction(RT-PCR).3.Acute myocardial infarction model of rats was constructed by occlusion of left coronary anterior descending branch.Chang of heart function was compared between post MI and before MI by echocardiogragm and electrocardiogram.4.80 inbred line Wister rats was random divided sham operation control group(A group,10 rats) and construction acute myocardial infarctionsurvived(AMI) group(70 rats),60 rats survival from operation were randomly and equally assigned to myocardial infarctionsurvived group(B group,15 rats),culture fluid transplantation group(C group,1 5 rats),BMMSC s activaed Notch signal transplantation group(D group,15 rats) and BMMSCs transplantation group(E group,15 rats).Cultuerd cells were labeled with DAPI 2 hours before cel ls transplantation.2 weeks after ligation of left coronary anterior descending branch,0.1ml volume of induced BMMSCs transferred with ICN,induced BMMSCs without transfection of ICN,culture fluid,and physiological saline were injected into the area of myocardial infarction,respectively.Echocardiography examinations were performed to evaluate heart function at day 1,28 after operation,respectively.Rats were sacrificed 28 days after operation,heart samples were fixed with formalin for pathologic examination. Morphologic change of heart samples were assessed by gross examination.Transplanted cells were located by fluorescence microscopy examination.Capillary density,which was identified by expression ofⅧfactor antibody,was counted in hearts,Desmin and troponinⅠantibody stain were used to identified the difeerntiation of transplanted cells.Expression of collagen and MMPs in rat's hearts was evaluated as well.Results 1.BMMSCs of rats was successfully segregated.Flow cytometry showed that cultured cells were positive for anti-CD29 antibody,anti-Flk-1 antibody,and anti-CD117 antibody.All of which confirmed that the induced BMMSCs differentiated into the myogenic cells.2.successfully constructed BMMSCs with Notch signal is activated without ligand through transfection of ICN through retrovirus-mediated gene transfer.We detect the express of ICN in BMMSCs after ICN transfection through RT-PCR.
3.Myocardial infarction of rats was successfully constructed.ECG showed that ST segment was depressed and heart rates was faster when coronary artery was obstructed,ST segment was elevated and QRS complex was wider,and ST segment was depressed and Q wave appeared 8 hours later.Left ventricle was enlarged,local myocardial dyskinesis was found,and left ventricle Ejection Fraction(EF) decreased obviously by echocardiogram.Left ventricle EF of the operated rats(62.35±3.49)%, 24 hours after operation was lower than that of the rats before operation(39.67±2.33)%and sham operation rats(60.52±4.75)(p＜0.01).HE stain of heart samples collected 4 weeks after operation displayed local scar tissues devoid of cardiomyocytes,suggesting the formation of myocardial infarction.4.HE stain showed there was irregular scar tissues in anterior wall of left ventricle in cell D and E group,where allogenic cells(fluorescent cells) were found.Scar tissues but not allogenic cells were found in A group.Transplanted cells were positive for desmin and troponinⅠantibody.Echocardiogram demonstrated that local myocardial dyskinesis disappeared,volume of left ventricle got smaller,and left ventricle EF was elevated.Results of statistics analysis were as follows:heart function of rats in D group was beter than that of E group, B group,and C group.Infarcted areas and thickness of rats in D group were beter than that of E group,B group,and C group.Capillary density in D group was much more than that of others groups.Expression of type 1 collagen and MMP-1 in rats in induced D group was weaker than that of others groups.Conclunions Transplanted cells were alive in infarct myocardium and diferentiated into myogenic cells.Transplantation of BMMSCs transferred with ICN into myocardial infarction increased angiogenesis in infarct myocardium,decreased synthesis of collagen and matrix metalloproteinase,alleviated cardiac remodeling,and improved heart function.Transplantation of BMMSCs transferred with ICN was useful and safe for the treatment of myocardial infarction.
引文
[1]Strauer BE,Brehm M,Zeus T,et al.Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans[J].Circulation,2002,106(15):1913-1918.
[2]张静,李庚山,李国草,等.骨髓间充质干细胞自体移植治疗阿霉素心肌病[J].微循环学杂志,2005,15(3):8-10.
[3]Minguell JJ,Erices A.Mesenchymal stem cells and the treatment of cardiac disease[J].Exp Biol Med(Maywood),2006,231(1):39-49.
[4]Epstein S E,Komowski R,Fuchs S,et al.Angiogenesis therapy:a midst the hype,the neglected potential for serious side effects[J].Circtdation,2001,104(1):115-119.
[5]Artavanis-Tsakonas S,Rand M D,Lake R J.Notch signaling:Cell fate control and signal integration in development[J].Science,1999,284(5415):770-776.
[6]Arias A,Zecchini V,Brennan K.CSL-independent Notch signalling:A checkpoint in cell fate decisions during development[J].Curr Opin Genet Dev,2002,12(5):524-533.
[7]Kojika S,Griffin JD.Notch receptors and hematopoiesis[J].Exp Hematol 2001;29(9):1041-1052.
[8]Wesley CS,Saez L.Notch responds differently to Delta and Wingless in cultured Drosophila cells[J].J Biol Chem 2000;275(13):9099-9101.
[9]Minguell J J,Erices A,Conget P.Mesenchymal stem cells[J].Exp Biol Med (Maywood),2001,226(6):507-520.
[10]Deans R J,Moseley A B.Mesenchymal stem cells:Biology and potential clinical uses[J].Exp Hematol,2000,28(8):875-884.
[11]鲁茁壮,吴祖泽,等.激活Notch信号通路促进骨髓间充质干细胞向成骨细胞分化[J].科学通报,2004,49(6):554-557.
[12]Kang TJ,Yeom JE,Lee HJ,Rho SH,Han H,Chae GT.Growth kinetics of human mesenchymal stem cells from bone marrow and umbilical cord blood[J].Acta Haematol 2004;112(4):230-233.
[13]Orlic D,Kajstura J,Chimenti S,et al.Mobilized bone marrow cell repair the infarcted heart,improving function and survival[J].Proc Natl Acad Sci USA,2001,98:(18) 10344-10349.
[14]Strauer B E,Brehm M,Zeus T,et al.Myocardial regeneration after interacoronary transplatation of human autogous stem cells following acute myocardial infarction[J].Dtsch Med Wschr,2001,126(34 35):932-938.
[15]Wollert KC,Meyer G P,Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction:the BOOST randomised controlled clinical trial[J].Lancet,2004,364(9429):141-148.
[1]Robert J Deans,Annemarie B Moseley.Mesenchymal stem cells:biology and potential clinical uses[J].Experimental Hematology,2000,8:875-884.
[2]Paolo Bianco,Mara Riminucci,Start Gronthos,et al.Bone marrow stromal stem cells:nature,biology,and potential applications[J].Stem Cells,2001,19:180-192.
[3]Gronthos S,Graves SE,Ohta S,et al.The STRO-1 positive fraction of adult human bonem arrow contains the osteogenic precursors[J].Blood,1994,84:4164-4173.
[4]Shigeyuki Wakitani,Tomoyuki Saito,Arnold I Caplan.Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacyt idine[J].Muscle & Nerve,1995,18:1417-1426.
[5]Constantinides PG,Taylor SM,Jones PA.Phenotypic conversion of cu-ltured mouse embryo cells by aza pyrimidine nucleosides[J].Dev Biol,1978,66:57-71.
[6]Shinji Tomita,Ren-Ke Li,Richard D Weisel,et al.Autologous transplantation of bone marrow cells improves damaged heart function[J].Circulation,1999,100[suppl Ⅱ]:Ⅱ-247-Ⅱ-256.
[7]Shinji Makino,Keiichi Fukuda,Shunichirou Miyoshi,et al.Cardiomyocytes can be generated from marrow stromal cells invitro[J].J Clin Invest,1999,103:697-705.
[8]Xu W,Zhang X,Qian H,et al.Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro[J].Exp Biol Meal,2004,299(7):623-631.
[9]程芮,王士雯,曹丰,等.5-氮胞苷浓度对体外骨髓间充质干细胞诱导分化为心肌样细胞的影响[J].中华老年多器官疾病杂志,2005,4(3):196-220.
[10]Shim WS,Jiang S,Wong P,et al.Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells[J].Biochem Biophys Res Commun,2004,324(2):481-488.
[11]Jih-Shiuan Wang,Dominique Shum-Tim,Edgar Chedrawy,et al.The coronary delivery of marrow stromal cells for myocardial regeneration pathophysiological and therapeutic implications[J].J Thorac Cardiovasc Surg,2001,122:699-675.
[1]Gage HF.Mammalian neural stem cells[J].Science,2000,287(8):1433-1438.
[2]Minguell JJ,Erices A,Conget P.Mesenchymal stem cells[J].Exp Biol Med(Maywood),2001,226(6):507-520.
[3]Deans RJ,Moseley AB.Mesenchymal stem cells:biology and potential clinical uses[J].Exp Hematol,2000,28(4):875-884.
[4]张近宝,顾春虎,刘维水,等.犬骨髓问充质干细胞可诱导分化为组织工程瓣间质种子细胞[J].心脏杂志,2006,18(5):489-491,495.
[5]徐瑾,王彬尧,王长谦,等.骨髓间充质干细胞在心肌梗死区的移植和分化对心肌梗死后心力衰竭的影响[J].心脏杂志,2006,18(2):138-142.
[6]王莹,龚卫琴,张珊红,等.骨髓间充质干细胞不同移植方法对心肌梗死大鼠心脏的保护作用[J].心脏杂志,2007,19(3):266-268.
[7]Minguell J J,Erices A.Mesenchymal stem cells and the treatment of cardiac disease[J].Exp BiolMed(Maywood),2006,231(1):39-49.
[8]Artavanis-Tsakonas S,Rand MD,Lake RJ.Notch signaling:cell fate control and signal integration in development[J].Science.1999,284(5415):770-776.
[9]Kojika S,Griffin JD.Notch receptors and hematopoiesis[J].Exp Hematol.2001;29(9):1041-1052.
[10]Wesley CS,Saez L.Notch responds differently to Delta and Wingless in cultured Drosophila cells[J].J Biol Chem.2000;275(13):9099-9101.
[11]Ross DA,Kadesch T.Consequences of Notch-mediated induction of Jagged1[J].Exp Cell Res.2004;296(2):173-182.
[12]Struhl G,Fitzgerald K,Greenwald I.Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo[J].Cell.1993,74(2):331-345.
[13]Nam Y,Weng AP,Aster JC,Blacklow SC.Structural requirements for assembly of the CSL intracellular Notchl.Master-mind-likel transcriptional activation complex[J].J Biol Chem.2003;278(23):21232-21239.
[14]Mumm JS,Kopan R.Notch signaling:from the outside in[J].Dev Biol.2000;228(2):151-165.
[15]邢莹,白瑞樱,等.人骨髓间充质干细胞向神经细胞分化过程中Notch通路信号分子表达的变化[J].生理学报,2007,59(3):267-272.
[1]Artavanis-Tsakonas S,Rand M D,Lake R J.Notch signaling:Cell fate control and signal integration in development[J].Science,1999,284(5415):770-776.
[2]Arias A,Zecchini V,Brennan K.CSL-independent Notch signalling:A checkpoint in cell fate decisions during development[J].Curt Opin Genet Dev,2002,12(5):524-533.
[3]鲁茁壮,吴祖泽,等.激活Notch信号通路促进骨髓间充质干细胞向成骨细胞分化[J].科学通报,2004,49(6):554-557.
[4]Taylor DA,Atldns BZ,Hungspreugs P,et al.Regeneratingf unctional myocardium:improved performance after skeletal myoblast transplantation[J].Nat Med 1998,4(8):929-933.
[5]王立新,高长青,自体骨骼肌成肌细胞心肌成形术的实验研究[J].中华医学杂志.2002,82(3):100-103.
[6]Suzuki K,Murtuza B,Suzuki N,et al.Intracoronary infusion of keletal myoblasts improves cardiac function in doxorubicin-induced heart failure[J].Circulation.2001,104(Supp Ⅱ):1213-1217.
[7]Jain M,DerSimonian H,Brenner DA,et al.Cell therapy attenuates deleterious ventdcular remodeling and improves cardiac performance after myocardial infarction[J].Circulation.2001,103(Supp Ⅱ):1920-1927
[8]Shinji Tomita,Ren-Ke Li,Richard D.Weisel,et al.Autologous transplantation of bone marrow cells improves damaged heart function[J].Circulation,1999,100[suppl Ⅱ]:Ⅱ-247-Ⅱ-256.
[9]Pawlush DG,Moore RL,Musch TI,et al.Echocardiographic evaluation of size,function,and mass of normal and hypertrophied rat ventdcles[J].J Appl Physiol.1993,74(5):2598-2605.
[10]Litwin SE,Katz SE,Morgan JP,et al.Serial echocardiographic assessment of left ventricular geometry and function after large myocardial in farction in the rat[J].Circulation.1994,89(1):345-354.
[11]De Simone G,Devereux RB,Wallerson DC.Echocardiographic assessment of left ventricular hypertrophy in rats using a simplified approach[J].Am J Hypertens.1994,7(6):555-558.
[12]Schwarz ER,Pollick C,Dow J,et al.A small animal model of non-ischemic cardiomyopathy and its evaluation by transthoracic echocardiography[J].Cardiovasc Res.1998,39(1):216-223.
[13]方和平,翟莉,吴振军等。多普勒超声心动图评价心肌梗死大鼠心功能的研究[J].铁道医学 2000,28(5):308-309.
[14]Kenneth W.Liechty,Yippi C.Mackenzie,Aimen EShaaban,et al.Human mese nchymal stem cells engraft and demonstrated site-specific differ entiation after in utero transplantation in ship[J].Nature Medicine,2000,6:1282-1286.
[15]Shinji Yomita,Ren-Ke Li,Richard D.Weisel,et al.Autologous transp lantation of bone marrow cells improves damaged heart function[J].Ci rculation,1999,100[supp Ⅱ]:Ⅱ-247-Ⅱ-256.
[16]Jih-Shiuan Wang,Dominique Shum-Tim,Edgar Chedrawy,et al.The coro nary delivery of marrows tromal cells for myocardial regeneration:path ophysiological and therapeutic implications[J].J Thorac Cardiovasc Surg,2001,122:699-675.
[17]Donald Orlic,Jan Kajstura,Stefano Chimenti,et al.Bone marrow cells re generate infarcted myocardium[J].Nature,2000,410:701-705.
[18]Catalin Toma,Mark F.Pittenger,Kevin S.Cahill,et al.Human mese nchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart[J].Circulation,2002,105:93-98.
[19]Baldwin ME,Stacker SA,Achen MG.Molecular control of lymphan giogenesis[J].Bioessays 2002;24:1030-1040.
[20]Nagy JA,Vasile E,Feng D,Sundberg C,Brown LF,Detmar MJ,et al.Va seular permeability factor/vascular endothelial growth factor induces L ymphangiogenesis as well as angiogenesis[J].J Exp Med 2002;196:1497-1506.
[21]Ohm JE,Gabrilovich DI,Sempowski GD,Kisseleva E,Parman KS,Nadaf S,et al.VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression[J].Blood 2003:101:4878-4886.
[22]Ohm JE,Carbone DE VEGF as a mediator of tumor-associated immuno deficiency[J].Immunol Res 2001;23:263-272.
[23]Lyden D,Hattori K,Dias S,Costa C,Blaikie P,Butros L,et al.Imp aired recruitment of bone-marrow-derived endothelial and hematopoieticp recursor cells blocks tumor angiogenesis and growth[J].Nat Med 2001;7:1194-1201.
[24]Rafii S,Lyden D,Benezra R,Hattori K,Heissi B.Vascular and haematopoietic stem cells:novel targets for anti-angiogenesis therapy[J]? Nat Rev Cancer,2002;2:826-835.
[25]Mann DR,Plant TM.Leptin and pubertal development[J].Semin Reprod Med 2002;20:93-102.
[26]Neufeld G;Cohen T,Gengrinovitch S,et al.Vascular endothelial growth factor(VEGF) and its receptors[J].FASEB J,1999,13(1):9-22.
[27]Clauss M.Molecular biology of the VEGF and the VEGF receptor family[J].Sem in Thromb Hemost,2000,26(5):561-569.
[28]Brown L P,Yeo K T,Brese B,et al.Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing[J].J Exp Med,1992,176(5):1375-1379.
[29]Unger EF,Banai S,Shou M,et al.[J].Am J Physiol,1994,266(4pt2):H1588-1595.
[30]Banai S,Jaklitsch MT,Shou M,et al.[J].Circulation,1994,89(5):2183-2189.
[31]Isner JM,Walsh K,Symes J,et al.[J].Circulation,1995,91(11):2687-2692.
[32]Juha Rutanen,Tuomas T.Rissanen,Johanna E.Markkanen,et al.Adenov iral Catheter-Mediated Intramyocardial Gene Transfer Using the Mature Form of Vascular Endothelial Growth Factor-D In ducesrransmural Angiogenesis in Porcine Heart[J].Circulation.2004:109:1029-1035.
[33]Kang HJ,Kim HS,Zhang SY,et al.Effects of intracoronary infusion of peripheral blood stem cells mobilised with granulocyte colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction:the MAGIC cell randomised clinical trial[J].Lancet,2004,363(9411):751-756.
[34]Wollert KC,Meyer GP,Lotz J,et al.Intracoronary autologous bone marrow cell transfer after myocardial infarction:the BOOST randomised controlled clinical trial[J].Lancet,2004,364(9429):141-148.
[1]Friedenstein AJ,Petrakova KV,Kurolesova AI,et al.Heterotypic transplants of bone marrow:analysis of precursor cells for osteogenic and hematopoietic tissues[J].Transplantation,1968,6:230-247.
[2]Trotha R,Hanck T,Konig W,et al.Rapid ribesequencing—an effective diagnostic tool for detecting microbial infection[J].Infect,2001,29:12-16.
[3]Wakitani S,Saito T,Caplan AI.Myogeni ccells derived from rat bone marrow mesenchymal stem cells exlxased to 5-azacytidine[J].Mule Nerve,1995,18:1417-1426.
[4]Makino S,Fukuda K,Miyoshi S,etal.Cardiomyocytes can be generated from manrrow stromal cells invitro[J].J Clin Invest,1999,103:697-705.
[5]Wang JS,Shum-Tlm D,Galipeau J,et al.Marrow stromal cells for cellular endiumyoplasty:feasility and potential clinical advantages[J].J Thorac cardiovasc Stag,2000,120:999-1002.
[6]Tomita S,Weisel RD.Autologous transplantation of bone marrow cells improves infarction heart function[J].Circulation,1999,100(Suppl Ⅱ):S247-S252.
[7]Fukuhara S,Tomita S,Yamashiro S,etal.Direct cell-cell interaction of cardiomyocytes is key for bone marrow stromal cells to go into cardiac lineage in vitro[J].J Thorac Cardiovasc Stag,2003,125:1470-1480.
[8]Toma C,Pittenger MF,Cahill KS,etal.Human mesenchyma stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart[J].Circulation,2002,105:93-98.
[9]Strauer BE,Brehm M,Zeus T,etal.Intracoronary human autologous stem cells transplantation for myocardial regeneration following myocardial infarction[J].Dtsch Med Wochenscher,2001,126:932-938.
[10]Assmus B,Schachiger V,Teupe C,et al.Transplantation of progenitor cells and regeneration enhancement in acute myocardia infarction[J].Circulation,2002,106:3009-3017.
[11]Perin EC,Dohmam HF,Borojevic R,et al.Transendo cardial,autologous bone marrow cell transplantation for severe,chronic is chemic heartfailure[J].Circulation,2003,107:2294-2302.
[12]Muller EJ,Kedes LH,Schwinger RH,et al.Cellular cardioplasty a novel approach to treat heart disease[J].Congest Heart Fail,2002,8:220-227.
[13]Hakuno D,Fukuda K,Makino S,etal.Bone marrow-derived regenerated cardimyocytes(CMG Cells)express functional adrenergic and muscarinic receptors[J].Circulation,2002,105:380-386.
[14]Kocher AA,Shuster MD,Szabolcs M7,et al.Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis,reduces remodeling and improves cardiac function[J].Nat Med,2001,7:430-436.
[15]Krampera M,Glennie S,Dyson J,etal.Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen specific T cells to their cognate peptide[J].Blood,200,101:3722-3729.
[16]Djouad F,Hence P,Bony C,et al.Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals[J].Blood,2003,102:3837-3844.
[17]Pak HN,Qayyum M,Kim DT,et al.Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction[J].Cardiovasc Electrophysiol,2003,14(8):841-848.
[18]Agbulut O,Vandervelde S,Al Attar N,et al.Comparison of human skeletal myoblasts and bone marrow-derived CD133+progenitors for the repair of infarcted myocardium[J].Am Coil Cardiol,2004,44(2):458-463.
[19]Dai W,Hale SL,Martin BJ,et al.Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium:short-and long-term effects[J].Circulation,2005,112(2):214-223.
[20]Weimar IS,Miranda N,Muller EJ,et al.Hepatocyte growth factor/scatter factor(HGF/SF) is produced by human bone marrow stromal cells and promotes proliferation,adhesion and survival of human hematopoietic progenitor cells(CD34+)[J].Exp Hematol,1998,29(6):885-894.
[21]Kinnaird T,Stabile E,Burnett MS,et al.Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms[J].Circ Res,2004,94(5):678-685.
[22]Kinnaird T,Stabile E,Burnett MS,et al.Local delivery of marrow derived stromal cells augments collateral perfusion through paracrine mechanisms[J].Circulation,2004,109(12):1543-1549.
[23]Haynesworth SE,Baber MA,Caplan AI.Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro:effects of dexame thasone and IL-1 alpha[J].Cell Physiol,1996,166(3):585-592.
[24]Gnecchi M,He H,Liang OD,et al.Paracrine action accounts formarked protection of ischemic heart by Akt-modified mesenchymal stem cells[J].Nat Med,2005,11(4):367-368.
[25]曹丰,裴雪涛,李艳华,等.移植时机对骨髓间充质干细胞修复梗死心肌的影响[J].第四军医大学学报,2005,26:22-27.
[26]Rangogiannis NG,Smith CW,Mark LE.The inflammatory response in myocardial infarction[J].Cardiovasc Res,2002,53:31-47.
[27]Rangogiannis NG,Mendoza LH,Lewallen M,et al.Induction and suppression of interferon-inducible protein 10 in reperfused myocardial infarcts may regulate angiogenesis[J].FASEB J,2001,15:1428-1430.
[28]Sockit T,Tamura Y,Shinohara H,et al.Senial Changes in serum VEGF and HGF in patients with acute myocardial infarction[J].Cardilology,2000,93:168-174.
[29]裴雪涛,程芮,曹丰,等.3种不同途径移植自体骨髓间充质干细胞治疗急性心肌梗死效果比[J].中华实验外科杂志,2005,12:1054-1056.
[30]Xu W,Zhang X,Qian H,et al.Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro[J].Exp Biol Med,2004,299(7):623-631.
[31]程芮,王士雯,曹丰,等.5-氮胞苷浓度对体外骨髓间充质干细胞诱导分化为心 肌样细胞的影响[J].中华老年多器官疾病杂志,2005,4(3):196-220.
[32]Shim WS,Jiang S,Wong P,et al.Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells[J].Biochem Biophys Res Commun,2004,324(2):481-488.
[33]Price MJ,Chou CC,Frantzen M,et al.Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties[J].Int J Cardiol,2006,111(2):231-239.
[34]Xu M,Wani M,Dai YS,et al.Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes[J].Circulation,2004,110(17):2658-2665.
[35]Yoon J,Shim WJ,Ro YM,et al.Transdifferentiation of mesenchymal stem cells into cardiomyocytes by direct cell-to-cell contact with neonatal cardiomyocyte but not adult cardiomyocytes[J].Ann Hematol,2005,84(11):715-721.
[36]Li H,Yu B,Zhang Y,et al.Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes[J].Biochem Biophys Res Commun,2006,341(2):320-325.
[37]Anversa P,Kajstura J,Leri A,et al.Life and death of cardiac stem cells:a paradigm shift in cardiac biology[J].Circulation,2006,113(11):1451-1463.
[38]Yamashita JK,Takano M,Hiraoka-Kanie M,et al.Prospective identification of cardiac progenitors by a novel single cell-based cardiomyocyte induction[J].FASEB J,2005,19(11):1534-1536.
[39]Matsuura K,Nagai T,Nishigaki N,et al.Adult Cardiac Sca-1-positive cells differentiate into beating cardiomyocytes[J].J Biol Chem,2004,297(12):11384-11391.
[40]Fazel S,Cimini M,Chen L,et al.Cardioprotective c-kit~+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines[J].J Clin Invest,2006,116(7):1865-1877.
[41]Yuasa S,Itabashi Y,Koshimizu U,et al.Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells[J].Nat Biotechnol,2005,23(5):607-611.
[42]van W ijk B,Moorman AF,van den Hoff MJ.Role of bone morphogenetic proteins in cardiac differentiation[J].Cardiovasc Res,2007,74(2):244-255.
[43]Wang J,Wynshaw Boris A.The canonical Wnt pathway in early mammalian embryogenesis and stem cellmaintenance/differentiation[J].Curr Opin Genet Dev,2004,14(5):533-539.
[44] Kuhl M. The WNT/calcium pathway: biochemical mediators,tools and future requirements[J]. Front Biosci,2004,9:967-974.
[45] Terami H, Hidaka K, Katsumata T, et al. Wntl1 facilitates embry onic stem cell differentiation to Nkx2.5-positive cardiomyocytes[J]. Biochem Biophys Res Commun,2004,325(3):968-975.
[46] Koyanagi M, Haendeler J, Badorff C, et al. Non-canonical Wnt signaling enhances differentiation of human circulating progenitor cells to cardiomyogenic cells[J]. J Biol Chem, 2005,280(17):16838-16842.
[47] Singh AM, Li FQ, Hamazaki T, et al. Chibby, an antagonistof the Wnt/p-Catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells[J].Circulation,2007,115(5):617-626.
[48] Rosenblatt-Velin N, Lepore MG, Cartoni C, et al. FGF-2 controls the differentiation of resident cardiac precursors into functional cardiomyocytes[J]. J ClinInvest,2005,115(7):1724-1733.
[49] Song H, Kwon K, Lim S, et al. Transfection of nesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions[J]. Mol Cells,2005,19(3):402-407.
[50] Kruithof BP, van W ijk B, Somi S, et al. BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage[J]. Dev Biol,2006,295(2):507-522.
[51] Marguerie A,Bajolle F, Zaffran S, et al. Congenital heart defects in Fgfr2-IIIb and Fgf10 mutantmice[J]. Cardiovasc Res,2006,71(1):50-60.
[52] Chau MD,Tuft R,Fogarty K, et al. Notch signaling plays a key role in cardiac cell differentiation[J].Mech Dev,2006,123(8):626-640.
[53] Nemir M,Croquelois A,Pedrazzini T,et al.Induction of cardiogenesis in embryonic stem cells via downregulation of notchl signaling[J]. Circ Res,2006,98(12):1471-1478.
[54] Li W, Ma N, OngLL, et al1.Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function[J].Stem Cells,2007,25(8): 2118-2127.
[55] Lee K, Majumdar MK, Buyaner D, et all.Human mesenchymal stem cells maintain transgene expression during expansion and differentiation[J].Mol Ther, 2001,3(6):857-866.
[56] Toma C, Pittenger MF, Cahill KS, et all Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adultmurine heart[J].Circulation,2002,105(1):932981
[57]Mangi AA,Noiseux N,Kong D,et al1.Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts[J].Nat Med,2003,9(9):1195-1201.
[58]Gnecchi M,He H,Noiseux N,et all.Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement[J].FASEB J,2006,20(6):661-669.
[59]Tang YL,Tang Y,Zhang YC,et al1.Improved graft mesenchymal stem cell survival in ischemic heartwith a hypoxia-regulated heme oxygenase-1vector[J].J Am Coil Cardiol,2005,46(7):1339-13501.
[60]Matsumoto R,Omura T,Yoshiyama M,et all.Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction[J].Arterioscler Thromb Vasc Biol,2005,25(6):1168-1173.
[61]Sun L,Cui M,Wang Z,et al1.Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat model of acute myocardial infarction[J].Biochem Biophys Res Commun,2007,357(3):779-784.
[62]Zhou YF,Yang XJ,Li HX,et all.Mesenchymal stem cells transfected with HCN2 genes by LentiV can be modified to be cardiac pacemaker cells[J].Med Hypotheses,2007,69(5):1093-1071.
[63]Guo YT,Li XY,Lu XC,et all.Bone marrow stem cells based SERCA2a gene therapy for heart failure after acute myocardium infarction[J].Zhonghua Yi Xue Za Zhi,2006,86(12):826-831.
[64]Yau TM,Kim C,Li G;et al1.Maximizing ventficular function with multimodal cell-based gene therapy[J].Circulation,2005,112(9 Suppl):Ⅱ23-Ⅱ28.
[65]Liu J,Hu Q,Wang Z,et all.Autologous stem cell transplantation for myocardial repair[J].Am J Physiol Heart Circ Physiol,2004,287(2):H501-H511.
[66]Xiang Z,Liao R,Kelly MS,et al1.Collagen-GAG scaffolds grafted onto myocardial infarcts in a rat model:a delivery vehicle for mesenchymal stem cells[J].Tissue Eng,2006,12(9):2467-2478.
[67]Davis ME,Hsieh PC,Takahashi T,et al1.Local myocardial insulin-like growth factor 1(IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy formyocardial infarction[J].Proc Natl Acad Sci USA,2006,103(21):8155-8160.
[68]McMullen NM,Pasumarthi KB.Donor cell transplantation for myocardial disease:does it complement current pharmacological therapies?[J].Can J Physiol Pharmacol,2007,85(1):1-15.
[69]Olivares EL,Costa-E-Sousa RH,Werneck-de-Castro JP,et al1.Cellular cardiomyoplasty in large myocardial infarction:can the beneficial effect be enhanced by ACE-inhibitor therapy?[J].Eur J Heart Fail,2007,9(627):558-567.
[70]Wang JA,Luo RH,Zhang X,et al1.Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction[J].J Zhejiang Univ Sci B,2006,7(8):641-647.
[71]Shake JG,Gruber PJ,Baumgartner WA,et al1.Mesenchymal stem cell implantation in a swine myocardial infarct model:engraftment and functional effectsl Ann Thorac Surg,2002,73(6):1919-1925.
[72]van Eickels M,Vetter H,Grohe C.Angiotensin-converting enzyme(ACE)inhibition attenuates insulin-like growth factor-Ⅰ(IGF-Ⅰ) induced cardiac fibroblast proliferationl[J].Br J Pharmacol,2000,131(8):1592-1596.
[73]Zhang D,Zhang F,Zhang Y,et al1.Combining erythropoietin infusion with intramyocardial delivery of bone marrow cells is more effective for cardiac repair[J].Transpl Int,2007,20(2):174-183.
[74]Xu R,Chen J,Cong X,et al1.Lovastatin protects mesenchymal stem cells against hypoxia-and serum deprivation-induced apoptosis by activation of PI3K/Akt and ERK1/21[J].J Cell Biochem,2008,103(1):256-269.
[75]Ogura T,Tanaka Y,Nakata T,et al1.Simvastatin reduces insulin-like growth factor-1 signaling in differentiating C2C12 mouse myoblast cells in an HMG-CoA reductase inhibition-independent manner[J].J Toxicol Sci,2007,32(1):57-67.
[76]张近宝,顾春虎,刘维水,等.犬骨髓间充质干细胞可诱导分化为组织工程瓣间质种子细胞[J].心脏杂志,2006,18(5):489-491,495.
[77]徐瑾,王彬尧,王长谦,等.骨髓间充质干细胞在心肌梗死区的移植和分化对心肌梗死后心力衰竭的影响[J].心脏杂志,2006,18(2):138-142.
[78]王莹,龚卫琴,张珊红,等.骨髓间充质干细胞不同移植方法对心肌梗死大鼠心脏的保护作用[J].心脏杂志,2007,19(3):266-268.
[79]Minguell JJ,Erices A.Mesenchymal stem cells and the treatment of cardiac disease[J].Exp BiolMed(Maywood),2006,231(1):39-49
[2]张静,李庚山,李国草,等.骨髓间充质干细胞自体移植治疗阿霉素心肌病[J].微循环学杂志,2005,15(3):8-10.
[3]Minguell JJ,Erices A.Mesenchymal stem cells and the treatment of cardiac disease[J].Exp Biol Med(Maywood),2006,231(1):39-49.
[4]Epstein S E,Komowski R,Fuchs S,et al.Angiogenesis therapy:a midst the hype,the neglected potential for serious side effects[J].Circtdation,2001,104(1):115-119.
[5]Artavanis-Tsakonas S,Rand M D,Lake R J.Notch signaling:Cell fate control and signal integration in development[J].Science,1999,284(5415):770-776.
[6]Arias A,Zecchini V,Brennan K.CSL-independent Notch signalling:A checkpoint in cell fate decisions during development[J].Curr Opin Genet Dev,2002,12(5):524-533.
[7]Kojika S,Griffin JD.Notch receptors and hematopoiesis[J].Exp Hematol 2001;29(9):1041-1052.
[8]Wesley CS,Saez L.Notch responds differently to Delta and Wingless in cultured Drosophila cells[J].J Biol Chem 2000;275(13):9099-9101.
[9]Minguell J J,Erices A,Conget P.Mesenchymal stem cells[J].Exp Biol Med (Maywood),2001,226(6):507-520.
[10]Deans R J,Moseley A B.Mesenchymal stem cells:Biology and potential clinical uses[J].Exp Hematol,2000,28(8):875-884.
[11]鲁茁壮,吴祖泽,等.激活Notch信号通路促进骨髓间充质干细胞向成骨细胞分化[J].科学通报,2004,49(6):554-557.
[12]Kang TJ,Yeom JE,Lee HJ,Rho SH,Han H,Chae GT.Growth kinetics of human mesenchymal stem cells from bone marrow and umbilical cord blood[J].Acta Haematol 2004;112(4):230-233.
[13]Orlic D,Kajstura J,Chimenti S,et al.Mobilized bone marrow cell repair the infarcted heart,improving function and survival[J].Proc Natl Acad Sci USA,2001,98:(18) 10344-10349.
[14]Strauer B E,Brehm M,Zeus T,et al.Myocardial regeneration after interacoronary transplatation of human autogous stem cells following acute myocardial infarction[J].Dtsch Med Wschr,2001,126(34 35):932-938.
[15]Wollert KC,Meyer G P,Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction:the BOOST randomised controlled clinical trial[J].Lancet,2004,364(9429):141-148.
[1]Robert J Deans,Annemarie B Moseley.Mesenchymal stem cells:biology and potential clinical uses[J].Experimental Hematology,2000,8:875-884.
[2]Paolo Bianco,Mara Riminucci,Start Gronthos,et al.Bone marrow stromal stem cells:nature,biology,and potential applications[J].Stem Cells,2001,19:180-192.
[3]Gronthos S,Graves SE,Ohta S,et al.The STRO-1 positive fraction of adult human bonem arrow contains the osteogenic precursors[J].Blood,1994,84:4164-4173.
[4]Shigeyuki Wakitani,Tomoyuki Saito,Arnold I Caplan.Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacyt idine[J].Muscle & Nerve,1995,18:1417-1426.
[5]Constantinides PG,Taylor SM,Jones PA.Phenotypic conversion of cu-ltured mouse embryo cells by aza pyrimidine nucleosides[J].Dev Biol,1978,66:57-71.
[6]Shinji Tomita,Ren-Ke Li,Richard D Weisel,et al.Autologous transplantation of bone marrow cells improves damaged heart function[J].Circulation,1999,100[suppl Ⅱ]:Ⅱ-247-Ⅱ-256.
[7]Shinji Makino,Keiichi Fukuda,Shunichirou Miyoshi,et al.Cardiomyocytes can be generated from marrow stromal cells invitro[J].J Clin Invest,1999,103:697-705.
[8]Xu W,Zhang X,Qian H,et al.Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro[J].Exp Biol Meal,2004,299(7):623-631.
[9]程芮,王士雯,曹丰,等.5-氮胞苷浓度对体外骨髓间充质干细胞诱导分化为心肌样细胞的影响[J].中华老年多器官疾病杂志,2005,4(3):196-220.
[10]Shim WS,Jiang S,Wong P,et al.Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells[J].Biochem Biophys Res Commun,2004,324(2):481-488.
[11]Jih-Shiuan Wang,Dominique Shum-Tim,Edgar Chedrawy,et al.The coronary delivery of marrow stromal cells for myocardial regeneration pathophysiological and therapeutic implications[J].J Thorac Cardiovasc Surg,2001,122:699-675.
[1]Gage HF.Mammalian neural stem cells[J].Science,2000,287(8):1433-1438.
[2]Minguell JJ,Erices A,Conget P.Mesenchymal stem cells[J].Exp Biol Med(Maywood),2001,226(6):507-520.
[3]Deans RJ,Moseley AB.Mesenchymal stem cells:biology and potential clinical uses[J].Exp Hematol,2000,28(4):875-884.
[4]张近宝,顾春虎,刘维水,等.犬骨髓问充质干细胞可诱导分化为组织工程瓣间质种子细胞[J].心脏杂志,2006,18(5):489-491,495.
[5]徐瑾,王彬尧,王长谦,等.骨髓间充质干细胞在心肌梗死区的移植和分化对心肌梗死后心力衰竭的影响[J].心脏杂志,2006,18(2):138-142.
[6]王莹,龚卫琴,张珊红,等.骨髓间充质干细胞不同移植方法对心肌梗死大鼠心脏的保护作用[J].心脏杂志,2007,19(3):266-268.
[7]Minguell J J,Erices A.Mesenchymal stem cells and the treatment of cardiac disease[J].Exp BiolMed(Maywood),2006,231(1):39-49.
[8]Artavanis-Tsakonas S,Rand MD,Lake RJ.Notch signaling:cell fate control and signal integration in development[J].Science.1999,284(5415):770-776.
[9]Kojika S,Griffin JD.Notch receptors and hematopoiesis[J].Exp Hematol.2001;29(9):1041-1052.
[10]Wesley CS,Saez L.Notch responds differently to Delta and Wingless in cultured Drosophila cells[J].J Biol Chem.2000;275(13):9099-9101.
[11]Ross DA,Kadesch T.Consequences of Notch-mediated induction of Jagged1[J].Exp Cell Res.2004;296(2):173-182.
[12]Struhl G,Fitzgerald K,Greenwald I.Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo[J].Cell.1993,74(2):331-345.
[13]Nam Y,Weng AP,Aster JC,Blacklow SC.Structural requirements for assembly of the CSL intracellular Notchl.Master-mind-likel transcriptional activation complex[J].J Biol Chem.2003;278(23):21232-21239.
[14]Mumm JS,Kopan R.Notch signaling:from the outside in[J].Dev Biol.2000;228(2):151-165.
[15]邢莹,白瑞樱,等.人骨髓间充质干细胞向神经细胞分化过程中Notch通路信号分子表达的变化[J].生理学报,2007,59(3):267-272.
[1]Artavanis-Tsakonas S,Rand M D,Lake R J.Notch signaling:Cell fate control and signal integration in development[J].Science,1999,284(5415):770-776.
[2]Arias A,Zecchini V,Brennan K.CSL-independent Notch signalling:A checkpoint in cell fate decisions during development[J].Curt Opin Genet Dev,2002,12(5):524-533.
[3]鲁茁壮,吴祖泽,等.激活Notch信号通路促进骨髓间充质干细胞向成骨细胞分化[J].科学通报,2004,49(6):554-557.
[4]Taylor DA,Atldns BZ,Hungspreugs P,et al.Regeneratingf unctional myocardium:improved performance after skeletal myoblast transplantation[J].Nat Med 1998,4(8):929-933.
[5]王立新,高长青,自体骨骼肌成肌细胞心肌成形术的实验研究[J].中华医学杂志.2002,82(3):100-103.
[6]Suzuki K,Murtuza B,Suzuki N,et al.Intracoronary infusion of keletal myoblasts improves cardiac function in doxorubicin-induced heart failure[J].Circulation.2001,104(Supp Ⅱ):1213-1217.
[7]Jain M,DerSimonian H,Brenner DA,et al.Cell therapy attenuates deleterious ventdcular remodeling and improves cardiac performance after myocardial infarction[J].Circulation.2001,103(Supp Ⅱ):1920-1927
[8]Shinji Tomita,Ren-Ke Li,Richard D.Weisel,et al.Autologous transplantation of bone marrow cells improves damaged heart function[J].Circulation,1999,100[suppl Ⅱ]:Ⅱ-247-Ⅱ-256.
[9]Pawlush DG,Moore RL,Musch TI,et al.Echocardiographic evaluation of size,function,and mass of normal and hypertrophied rat ventdcles[J].J Appl Physiol.1993,74(5):2598-2605.
[10]Litwin SE,Katz SE,Morgan JP,et al.Serial echocardiographic assessment of left ventricular geometry and function after large myocardial in farction in the rat[J].Circulation.1994,89(1):345-354.
[11]De Simone G,Devereux RB,Wallerson DC.Echocardiographic assessment of left ventricular hypertrophy in rats using a simplified approach[J].Am J Hypertens.1994,7(6):555-558.
[12]Schwarz ER,Pollick C,Dow J,et al.A small animal model of non-ischemic cardiomyopathy and its evaluation by transthoracic echocardiography[J].Cardiovasc Res.1998,39(1):216-223.
[13]方和平,翟莉,吴振军等。多普勒超声心动图评价心肌梗死大鼠心功能的研究[J].铁道医学 2000,28(5):308-309.
[14]Kenneth W.Liechty,Yippi C.Mackenzie,Aimen EShaaban,et al.Human mese nchymal stem cells engraft and demonstrated site-specific differ entiation after in utero transplantation in ship[J].Nature Medicine,2000,6:1282-1286.
[15]Shinji Yomita,Ren-Ke Li,Richard D.Weisel,et al.Autologous transp lantation of bone marrow cells improves damaged heart function[J].Ci rculation,1999,100[supp Ⅱ]:Ⅱ-247-Ⅱ-256.
[16]Jih-Shiuan Wang,Dominique Shum-Tim,Edgar Chedrawy,et al.The coro nary delivery of marrows tromal cells for myocardial regeneration:path ophysiological and therapeutic implications[J].J Thorac Cardiovasc Surg,2001,122:699-675.
[17]Donald Orlic,Jan Kajstura,Stefano Chimenti,et al.Bone marrow cells re generate infarcted myocardium[J].Nature,2000,410:701-705.
[18]Catalin Toma,Mark F.Pittenger,Kevin S.Cahill,et al.Human mese nchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart[J].Circulation,2002,105:93-98.
[19]Baldwin ME,Stacker SA,Achen MG.Molecular control of lymphan giogenesis[J].Bioessays 2002;24:1030-1040.
[20]Nagy JA,Vasile E,Feng D,Sundberg C,Brown LF,Detmar MJ,et al.Va seular permeability factor/vascular endothelial growth factor induces L ymphangiogenesis as well as angiogenesis[J].J Exp Med 2002;196:1497-1506.
[21]Ohm JE,Gabrilovich DI,Sempowski GD,Kisseleva E,Parman KS,Nadaf S,et al.VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression[J].Blood 2003:101:4878-4886.
[22]Ohm JE,Carbone DE VEGF as a mediator of tumor-associated immuno deficiency[J].Immunol Res 2001;23:263-272.
[23]Lyden D,Hattori K,Dias S,Costa C,Blaikie P,Butros L,et al.Imp aired recruitment of bone-marrow-derived endothelial and hematopoieticp recursor cells blocks tumor angiogenesis and growth[J].Nat Med 2001;7:1194-1201.
[24]Rafii S,Lyden D,Benezra R,Hattori K,Heissi B.Vascular and haematopoietic stem cells:novel targets for anti-angiogenesis therapy[J]? Nat Rev Cancer,2002;2:826-835.
[25]Mann DR,Plant TM.Leptin and pubertal development[J].Semin Reprod Med 2002;20:93-102.
[26]Neufeld G;Cohen T,Gengrinovitch S,et al.Vascular endothelial growth factor(VEGF) and its receptors[J].FASEB J,1999,13(1):9-22.
[27]Clauss M.Molecular biology of the VEGF and the VEGF receptor family[J].Sem in Thromb Hemost,2000,26(5):561-569.
[28]Brown L P,Yeo K T,Brese B,et al.Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing[J].J Exp Med,1992,176(5):1375-1379.
[29]Unger EF,Banai S,Shou M,et al.[J].Am J Physiol,1994,266(4pt2):H1588-1595.
[30]Banai S,Jaklitsch MT,Shou M,et al.[J].Circulation,1994,89(5):2183-2189.
[31]Isner JM,Walsh K,Symes J,et al.[J].Circulation,1995,91(11):2687-2692.
[32]Juha Rutanen,Tuomas T.Rissanen,Johanna E.Markkanen,et al.Adenov iral Catheter-Mediated Intramyocardial Gene Transfer Using the Mature Form of Vascular Endothelial Growth Factor-D In ducesrransmural Angiogenesis in Porcine Heart[J].Circulation.2004:109:1029-1035.
[33]Kang HJ,Kim HS,Zhang SY,et al.Effects of intracoronary infusion of peripheral blood stem cells mobilised with granulocyte colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction:the MAGIC cell randomised clinical trial[J].Lancet,2004,363(9411):751-756.
[34]Wollert KC,Meyer GP,Lotz J,et al.Intracoronary autologous bone marrow cell transfer after myocardial infarction:the BOOST randomised controlled clinical trial[J].Lancet,2004,364(9429):141-148.
[1]Friedenstein AJ,Petrakova KV,Kurolesova AI,et al.Heterotypic transplants of bone marrow:analysis of precursor cells for osteogenic and hematopoietic tissues[J].Transplantation,1968,6:230-247.
[2]Trotha R,Hanck T,Konig W,et al.Rapid ribesequencing—an effective diagnostic tool for detecting microbial infection[J].Infect,2001,29:12-16.
[3]Wakitani S,Saito T,Caplan AI.Myogeni ccells derived from rat bone marrow mesenchymal stem cells exlxased to 5-azacytidine[J].Mule Nerve,1995,18:1417-1426.
[4]Makino S,Fukuda K,Miyoshi S,etal.Cardiomyocytes can be generated from manrrow stromal cells invitro[J].J Clin Invest,1999,103:697-705.
[5]Wang JS,Shum-Tlm D,Galipeau J,et al.Marrow stromal cells for cellular endiumyoplasty:feasility and potential clinical advantages[J].J Thorac cardiovasc Stag,2000,120:999-1002.
[6]Tomita S,Weisel RD.Autologous transplantation of bone marrow cells improves infarction heart function[J].Circulation,1999,100(Suppl Ⅱ):S247-S252.
[7]Fukuhara S,Tomita S,Yamashiro S,etal.Direct cell-cell interaction of cardiomyocytes is key for bone marrow stromal cells to go into cardiac lineage in vitro[J].J Thorac Cardiovasc Stag,2003,125:1470-1480.
[8]Toma C,Pittenger MF,Cahill KS,etal.Human mesenchyma stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart[J].Circulation,2002,105:93-98.
[9]Strauer BE,Brehm M,Zeus T,etal.Intracoronary human autologous stem cells transplantation for myocardial regeneration following myocardial infarction[J].Dtsch Med Wochenscher,2001,126:932-938.
[10]Assmus B,Schachiger V,Teupe C,et al.Transplantation of progenitor cells and regeneration enhancement in acute myocardia infarction[J].Circulation,2002,106:3009-3017.
[11]Perin EC,Dohmam HF,Borojevic R,et al.Transendo cardial,autologous bone marrow cell transplantation for severe,chronic is chemic heartfailure[J].Circulation,2003,107:2294-2302.
[12]Muller EJ,Kedes LH,Schwinger RH,et al.Cellular cardioplasty a novel approach to treat heart disease[J].Congest Heart Fail,2002,8:220-227.
[13]Hakuno D,Fukuda K,Makino S,etal.Bone marrow-derived regenerated cardimyocytes(CMG Cells)express functional adrenergic and muscarinic receptors[J].Circulation,2002,105:380-386.
[14]Kocher AA,Shuster MD,Szabolcs M7,et al.Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis,reduces remodeling and improves cardiac function[J].Nat Med,2001,7:430-436.
[15]Krampera M,Glennie S,Dyson J,etal.Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen specific T cells to their cognate peptide[J].Blood,200,101:3722-3729.
[16]Djouad F,Hence P,Bony C,et al.Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals[J].Blood,2003,102:3837-3844.
[17]Pak HN,Qayyum M,Kim DT,et al.Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction[J].Cardiovasc Electrophysiol,2003,14(8):841-848.
[18]Agbulut O,Vandervelde S,Al Attar N,et al.Comparison of human skeletal myoblasts and bone marrow-derived CD133+progenitors for the repair of infarcted myocardium[J].Am Coil Cardiol,2004,44(2):458-463.
[19]Dai W,Hale SL,Martin BJ,et al.Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium:short-and long-term effects[J].Circulation,2005,112(2):214-223.
[20]Weimar IS,Miranda N,Muller EJ,et al.Hepatocyte growth factor/scatter factor(HGF/SF) is produced by human bone marrow stromal cells and promotes proliferation,adhesion and survival of human hematopoietic progenitor cells(CD34+)[J].Exp Hematol,1998,29(6):885-894.
[21]Kinnaird T,Stabile E,Burnett MS,et al.Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms[J].Circ Res,2004,94(5):678-685.
[22]Kinnaird T,Stabile E,Burnett MS,et al.Local delivery of marrow derived stromal cells augments collateral perfusion through paracrine mechanisms[J].Circulation,2004,109(12):1543-1549.
[23]Haynesworth SE,Baber MA,Caplan AI.Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro:effects of dexame thasone and IL-1 alpha[J].Cell Physiol,1996,166(3):585-592.
[24]Gnecchi M,He H,Liang OD,et al.Paracrine action accounts formarked protection of ischemic heart by Akt-modified mesenchymal stem cells[J].Nat Med,2005,11(4):367-368.
[25]曹丰,裴雪涛,李艳华,等.移植时机对骨髓间充质干细胞修复梗死心肌的影响[J].第四军医大学学报,2005,26:22-27.
[26]Rangogiannis NG,Smith CW,Mark LE.The inflammatory response in myocardial infarction[J].Cardiovasc Res,2002,53:31-47.
[27]Rangogiannis NG,Mendoza LH,Lewallen M,et al.Induction and suppression of interferon-inducible protein 10 in reperfused myocardial infarcts may regulate angiogenesis[J].FASEB J,2001,15:1428-1430.
[28]Sockit T,Tamura Y,Shinohara H,et al.Senial Changes in serum VEGF and HGF in patients with acute myocardial infarction[J].Cardilology,2000,93:168-174.
[29]裴雪涛,程芮,曹丰,等.3种不同途径移植自体骨髓间充质干细胞治疗急性心肌梗死效果比[J].中华实验外科杂志,2005,12:1054-1056.
[30]Xu W,Zhang X,Qian H,et al.Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro[J].Exp Biol Med,2004,299(7):623-631.
[31]程芮,王士雯,曹丰,等.5-氮胞苷浓度对体外骨髓间充质干细胞诱导分化为心 肌样细胞的影响[J].中华老年多器官疾病杂志,2005,4(3):196-220.
[32]Shim WS,Jiang S,Wong P,et al.Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells[J].Biochem Biophys Res Commun,2004,324(2):481-488.
[33]Price MJ,Chou CC,Frantzen M,et al.Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties[J].Int J Cardiol,2006,111(2):231-239.
[34]Xu M,Wani M,Dai YS,et al.Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes[J].Circulation,2004,110(17):2658-2665.
[35]Yoon J,Shim WJ,Ro YM,et al.Transdifferentiation of mesenchymal stem cells into cardiomyocytes by direct cell-to-cell contact with neonatal cardiomyocyte but not adult cardiomyocytes[J].Ann Hematol,2005,84(11):715-721.
[36]Li H,Yu B,Zhang Y,et al.Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes[J].Biochem Biophys Res Commun,2006,341(2):320-325.
[37]Anversa P,Kajstura J,Leri A,et al.Life and death of cardiac stem cells:a paradigm shift in cardiac biology[J].Circulation,2006,113(11):1451-1463.
[38]Yamashita JK,Takano M,Hiraoka-Kanie M,et al.Prospective identification of cardiac progenitors by a novel single cell-based cardiomyocyte induction[J].FASEB J,2005,19(11):1534-1536.
[39]Matsuura K,Nagai T,Nishigaki N,et al.Adult Cardiac Sca-1-positive cells differentiate into beating cardiomyocytes[J].J Biol Chem,2004,297(12):11384-11391.
[40]Fazel S,Cimini M,Chen L,et al.Cardioprotective c-kit~+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines[J].J Clin Invest,2006,116(7):1865-1877.
[41]Yuasa S,Itabashi Y,Koshimizu U,et al.Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells[J].Nat Biotechnol,2005,23(5):607-611.
[42]van W ijk B,Moorman AF,van den Hoff MJ.Role of bone morphogenetic proteins in cardiac differentiation[J].Cardiovasc Res,2007,74(2):244-255.
[43]Wang J,Wynshaw Boris A.The canonical Wnt pathway in early mammalian embryogenesis and stem cellmaintenance/differentiation[J].Curr Opin Genet Dev,2004,14(5):533-539.
[44] Kuhl M. The WNT/calcium pathway: biochemical mediators,tools and future requirements[J]. Front Biosci,2004,9:967-974.
[45] Terami H, Hidaka K, Katsumata T, et al. Wntl1 facilitates embry onic stem cell differentiation to Nkx2.5-positive cardiomyocytes[J]. Biochem Biophys Res Commun,2004,325(3):968-975.
[46] Koyanagi M, Haendeler J, Badorff C, et al. Non-canonical Wnt signaling enhances differentiation of human circulating progenitor cells to cardiomyogenic cells[J]. J Biol Chem, 2005,280(17):16838-16842.
[47] Singh AM, Li FQ, Hamazaki T, et al. Chibby, an antagonistof the Wnt/p-Catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells[J].Circulation,2007,115(5):617-626.
[48] Rosenblatt-Velin N, Lepore MG, Cartoni C, et al. FGF-2 controls the differentiation of resident cardiac precursors into functional cardiomyocytes[J]. J ClinInvest,2005,115(7):1724-1733.
[49] Song H, Kwon K, Lim S, et al. Transfection of nesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions[J]. Mol Cells,2005,19(3):402-407.
[50] Kruithof BP, van W ijk B, Somi S, et al. BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage[J]. Dev Biol,2006,295(2):507-522.
[51] Marguerie A,Bajolle F, Zaffran S, et al. Congenital heart defects in Fgfr2-IIIb and Fgf10 mutantmice[J]. Cardiovasc Res,2006,71(1):50-60.
[52] Chau MD,Tuft R,Fogarty K, et al. Notch signaling plays a key role in cardiac cell differentiation[J].Mech Dev,2006,123(8):626-640.
[53] Nemir M,Croquelois A,Pedrazzini T,et al.Induction of cardiogenesis in embryonic stem cells via downregulation of notchl signaling[J]. Circ Res,2006,98(12):1471-1478.
[54] Li W, Ma N, OngLL, et al1.Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function[J].Stem Cells,2007,25(8): 2118-2127.
[55] Lee K, Majumdar MK, Buyaner D, et all.Human mesenchymal stem cells maintain transgene expression during expansion and differentiation[J].Mol Ther, 2001,3(6):857-866.
[56] Toma C, Pittenger MF, Cahill KS, et all Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adultmurine heart[J].Circulation,2002,105(1):932981
[57]Mangi AA,Noiseux N,Kong D,et al1.Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts[J].Nat Med,2003,9(9):1195-1201.
[58]Gnecchi M,He H,Noiseux N,et all.Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement[J].FASEB J,2006,20(6):661-669.
[59]Tang YL,Tang Y,Zhang YC,et al1.Improved graft mesenchymal stem cell survival in ischemic heartwith a hypoxia-regulated heme oxygenase-1vector[J].J Am Coil Cardiol,2005,46(7):1339-13501.
[60]Matsumoto R,Omura T,Yoshiyama M,et all.Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction[J].Arterioscler Thromb Vasc Biol,2005,25(6):1168-1173.
[61]Sun L,Cui M,Wang Z,et al1.Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat model of acute myocardial infarction[J].Biochem Biophys Res Commun,2007,357(3):779-784.
[62]Zhou YF,Yang XJ,Li HX,et all.Mesenchymal stem cells transfected with HCN2 genes by LentiV can be modified to be cardiac pacemaker cells[J].Med Hypotheses,2007,69(5):1093-1071.
[63]Guo YT,Li XY,Lu XC,et all.Bone marrow stem cells based SERCA2a gene therapy for heart failure after acute myocardium infarction[J].Zhonghua Yi Xue Za Zhi,2006,86(12):826-831.
[64]Yau TM,Kim C,Li G;et al1.Maximizing ventficular function with multimodal cell-based gene therapy[J].Circulation,2005,112(9 Suppl):Ⅱ23-Ⅱ28.
[65]Liu J,Hu Q,Wang Z,et all.Autologous stem cell transplantation for myocardial repair[J].Am J Physiol Heart Circ Physiol,2004,287(2):H501-H511.
[66]Xiang Z,Liao R,Kelly MS,et al1.Collagen-GAG scaffolds grafted onto myocardial infarcts in a rat model:a delivery vehicle for mesenchymal stem cells[J].Tissue Eng,2006,12(9):2467-2478.
[67]Davis ME,Hsieh PC,Takahashi T,et al1.Local myocardial insulin-like growth factor 1(IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy formyocardial infarction[J].Proc Natl Acad Sci USA,2006,103(21):8155-8160.
[68]McMullen NM,Pasumarthi KB.Donor cell transplantation for myocardial disease:does it complement current pharmacological therapies?[J].Can J Physiol Pharmacol,2007,85(1):1-15.
[69]Olivares EL,Costa-E-Sousa RH,Werneck-de-Castro JP,et al1.Cellular cardiomyoplasty in large myocardial infarction:can the beneficial effect be enhanced by ACE-inhibitor therapy?[J].Eur J Heart Fail,2007,9(627):558-567.
[70]Wang JA,Luo RH,Zhang X,et al1.Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction[J].J Zhejiang Univ Sci B,2006,7(8):641-647.
[71]Shake JG,Gruber PJ,Baumgartner WA,et al1.Mesenchymal stem cell implantation in a swine myocardial infarct model:engraftment and functional effectsl Ann Thorac Surg,2002,73(6):1919-1925.
[72]van Eickels M,Vetter H,Grohe C.Angiotensin-converting enzyme(ACE)inhibition attenuates insulin-like growth factor-Ⅰ(IGF-Ⅰ) induced cardiac fibroblast proliferationl[J].Br J Pharmacol,2000,131(8):1592-1596.
[73]Zhang D,Zhang F,Zhang Y,et al1.Combining erythropoietin infusion with intramyocardial delivery of bone marrow cells is more effective for cardiac repair[J].Transpl Int,2007,20(2):174-183.
[74]Xu R,Chen J,Cong X,et al1.Lovastatin protects mesenchymal stem cells against hypoxia-and serum deprivation-induced apoptosis by activation of PI3K/Akt and ERK1/21[J].J Cell Biochem,2008,103(1):256-269.
[75]Ogura T,Tanaka Y,Nakata T,et al1.Simvastatin reduces insulin-like growth factor-1 signaling in differentiating C2C12 mouse myoblast cells in an HMG-CoA reductase inhibition-independent manner[J].J Toxicol Sci,2007,32(1):57-67.
[76]张近宝,顾春虎,刘维水,等.犬骨髓间充质干细胞可诱导分化为组织工程瓣间质种子细胞[J].心脏杂志,2006,18(5):489-491,495.
[77]徐瑾,王彬尧,王长谦,等.骨髓间充质干细胞在心肌梗死区的移植和分化对心肌梗死后心力衰竭的影响[J].心脏杂志,2006,18(2):138-142.
[78]王莹,龚卫琴,张珊红,等.骨髓间充质干细胞不同移植方法对心肌梗死大鼠心脏的保护作用[J].心脏杂志,2007,19(3):266-268.
[79]Minguell JJ,Erices A.Mesenchymal stem cells and the treatment of cardiac disease[J].Exp BiolMed(Maywood),2006,231(1):39-49