摘要
背景
颅脑创伤对于人体健康危害极大,是现代社会致死率及致残率极高的疾病之一,尤其是对于年龄小于45岁的中青年人群。创伤后的一系列复杂病理生理学变化导致微循环障碍,血脑屏障通透性增高,神经元死亡,以及神经功能障碍。对于脑创伤的研究注重于伤后脑血流、脑代谢、脑水肿、颅高压、电解质平衡以及脑组织形态学改变的研究。尽管对于颅脑创伤后的病理生理学机制的研究有了很大发展,但是对于颅脑创伤的治疗方法还是较为局限,主要基于伤后的对症支持治疗。越来越多的学者意识到促进脑创伤区域血循环的恢复,对于大脑神经功能的恢复起到至关重要的作用。已有研究表明内皮祖细胞(endothelial progenitor cells, EPCs)可以促进血管新生,并己在多种体内研究中证实具有血管生成及促进损伤恢复的作用。血培养内皮祖细胞又称为内皮集落形成细胞(Endothelial colony-forming cells, ECFCs)是EPCs的同源亚型,具有更强的细胞增殖潜能并且表达更多的血管内皮生长因子受体。ECFCs移植治疗是当前研究的热点。
目的：
在颅脑创伤小鼠模型中证实循环血中内皮祖细胞在创伤急性期可以归巢定位于脑创伤区域,并探索移植血培养内皮祖细胞对创伤后神经功能的影响,为临床治疗颅脑创伤提供新的治疗策略。
方法：
应用梯度离心法分离新鲜脐静脉血提取单个核细胞(MNCs),将所获得的MNCs采用贴壁培养的方法获取血培养EPCs (ECFCs)集落,并在体外培养、扩增,采用细胞免疫荧光法检测所获ECFCs的细胞表面标记。
应用液压打击设备制备颅脑损伤免疫缺陷小鼠模型并将其随机分为三组,包括ECFCs移植组,PBS注射组和单纯打击组,将培养ECFCs由尾静脉注射入小鼠体内。应用性别错配实验,即将所获来源于男性胎儿脐带血的ECFCs由尾静脉移植入创伤后雌性小鼠体内,采用人Y染色体特异性探针并利用荧光原位杂交技术技术检测移植ECFCs的归巢。
应用免疫组化和Western blot的方法检测小鼠创伤脑组织区域的微血管密度以及细胞因子表达的变化,分析血管新生与神经生物学功能恢复的关系。
应用改良神经功能评分(mNSS)和Morris水迷宫分别评价移植ECFCs后神经行为学功能恢复和空间学习功能改善。
结果：
人脐血源的ECFCs移植后24小时在小鼠损伤脑组织部位被检测到,mNSS评分以及水迷宫实验证明移植ECFCs组神经功能损害较PBS注射组和单纯打击组有明显减少(P<0.05),同时移植组脑损伤侧的微血管密度(MVD)明显增加,细胞因子SDF1和VEGF表达较其他两对照组明显增高(P<0.05)。微血管密度与mNSS评分呈负相关。
结论：
脐血源的ECFCs作为标志证明了循环血中EPCs能够归巢到脑损伤区域,移植ECFCs能够有效促进神经及血管的修复,并且改善了TBI后长期的神经功能,ECFCs移植未来可能是治疗脑外伤潜在的细胞治疗方法。
Background
Traumatic brain injury is greatly harmful to human health, and it is one of the diseases with high mortality and disability rate of modern society, especially for middle-aged people younger than45-year-old. A series of complex post-traumatic pathophysiology cause microcirculation disturbance, increased permeability of the blood-brain barrier, neuronal death and neurological dysfunction. The study of traumatic brain injury was focused on the cerebral blood flow, metabolism, brain edema, intracranial hypertension, electrolyte balance, and brain tissue morphology changes. Although many research areas had made significant progress in the pathophysiological mechanisms after traumatic brain injury, the treatment of traumatic brain injury is still relatively limited, and based mainly on symptomatic and supportive treatment after the TBI. More and more investigators realize that the recovery of blood circulation of TBI area play a crucial role for the neurologic improvement. It has been tested that endothelial progenitor cells (EPCs) can increase the angiogenesis and promote the recovery of injury in many in vivo studies. Endothelial colony-forming cells (ECFCs) are homologous subtype of EPCs, with the stronger cellular proliferative potential and the more expression of vascular endothelial growth factor receptor. The transplantation of ECFCs for some diseases is a research hotspot currently.
Objective
We are in order to confirm that the endothelial progenitor cells in the circulating blood can homing and locate in the area of traumatic brain injury in a TBI mouse model in the acute phase of trauma, explore the transplanted blood endothelial progenitor cells cultured could improve nerve function in post-traumatic, and find a new therapeutic strategies for clinical treatment of TBI.
Methods
The way of gradient centrifugation was used to isolate the mononuclear cells (MNCs) from the fresh umbilical vein, and then the MNCs was cultured by the adherent culture method to get ECFCs colony, and proliferated in vitro. The cells obtained were detected by immunofluorescence to check the cell surface markers of ECFCs. Youth female nude mice received fluid percussion and were divided into3groups, the ECFCs treated group, the PBS treated group and without infusion group. A method of sex-mismatched was used to design the experiment. The cultured ECFCs from boys were infused by tail vein into female mice. The transplanted ECFCs'homing was detected by the way of fluorescence in situ hybridization (FISH) and used the Y chromosome-specific probes of human. Modified neurological severity score (Mnss) was used to evaluate the recovery of neurological function of TBI mice after transplantation, and the Morris water maze was used to evaluate the special learning memory deficit. The cytokines (VEGF and SDF1) expression of injured area was assessed by western blot, and the microvascular density (MVD) was used the way of immunohistochemistry. The relationship of angiogenesis and neurological functional recovery was analyzed at last.
Results
ECFCs from donor were detected in the injured brain24hours after infusion. mNSS and MWM tests presented that the rate of neurological disability was significantly reduced in mice received ECFCs (P<0.05) and the ability of learning and memory improved greatly in the same group (P<0.05). Mice received with ECFCs had increased microvessel density (MVD), and the expression of cytokines including SDF1and VEGF in injured brain tissue.The increased microvascular density was negatively correlated with the mNSS.
Conclusion
The ECFCs form cord blood could home to the injured brain area, and it could effectively increase the angiogenesis, promote the recovery of neurological function and improved long-term outcome after TBI. The findings suggest that ECFCs from human umbilical cord blood hold great potentials of cell therapy in patients after TBI.
引文
[1]Werner C, Engelhard K. Pathophysiology of traumatic brain injury [J]. British journal of anaesthesia,2007,99(1):4-9.
[2]Cunningham AS, Salvador R, Coles JP, et al. Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury [J]. Brain:a journal of neurology,2005,128(Pt 8):1931-1942.
[3]Fagel DM, Ganat Y, Silbereis J, et al. Cortical neurogenesis enhanced by chronic perinatal hypoxia [J]. Exp Neurol,2006,199(1):77-91.
[4]Li Q, Michaud M, Stewart W, et al. Modeling the neurovascular niche:Murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn [J]. J Neurosci Res,2008,86(6):1227-1242.
[5]Li Q, Ford MC, Lavik EB, et al. Modeling the neurovascular niche:Vegf-and bdnf-mediated cross-talk between neural stem cells and endothelial cells:An in vitro study [J]. J Neurosci Res,2006,84(8):1656-1668.
[6]Ward NL, Lamanna JC. The neurovascular unit and its growth factors: Coordinated response in the vascular and nervous systems [J]. Neurological research,2004,26(8):870-883.
[7]Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis [J]. J Comp Neurol,2000,425(4):479-494.
[8]Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis [J]. Science,1997,275(5302):964-967.
[9]Lara-Hernandez R, Lozano-Vilardell P, Blanes P, et al. Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients with critical limb ischemia [J]. Annals of vascular surgery,2010,24(2):287-294.
[10]Lee CW, Huang PH, Huang SS, et al. Decreased circulating endothelial progenitor cell levels and function in essential hypertensive patients with electrocardiographic left ventricular hypertrophy [J]. Hypertension research official journal of the Japanese Society of Hypertension,2011,34(9):999-1003.
[11]Bogoslovsky T, Chaudhry A, Latour L, et al. Endothelial progenitor cells correlate with lesion volume and growth in acute stroke [J]. Neurology, 2010,75(23):2059-2062.
[12]Liu L, Liu H, Jiao J, et al. Changes in circulating human endothelial progenitor cells after brain injury [J]. J Neurotrauma,2007,24(6):936-943.
[13]Kao CH, Chen SH, Chio CC, et al. Human umbilical cord blood-derived cd34+ cells may attenuate spinal cord injury by stimulating vascular endothelial and neurotrophic factors [J]. Shock,2008,29(1):49-55.
[14]Shintani S, Murohara T, Ikeda H, et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation [J]. Circulation,2001,103(6):897-903.
[15]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 [J]. Experimental hematology, 2002,30(8):967-972.
[16]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 [J]. Lancet, 2002,360(9331):427-435.
[17]Huang PP, Li SZ, Han MZ, et al. Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities [J]. Thrombosis and haemostasis, 2004,91(3):606-609.
[18]Erbs S, Linke A, Adams V, et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion:First randomized and placebo-controlled study [J]. Circulation research,2005,97(8):756-762.
[19]Renault MA, Losordo DW. Therapeutic myocardial angiogenesis [J]. Microvascular research,2007,74(2-3):159-171.
[20]Jujo K, Ii M, Losordo DW. Endothelial progenitor cells in neovascularization of infarcted myocardium [J]. Journal of molecular and cellular cardiology, 2008,45(4):530-544.
[21]Sobrino T, Hurtado O, Moro MA, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome [J]. Stroke; a journal of cerebral circulation,2007,38(10):2759-2764.
[22]Chu K, Jung KH, Lee ST, et al. Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke [J]. Stroke; a journal of cerebral circulation,2008,39(5):1441-1447.
[23]Gong D, Hao M, Liu L, et al. Prognostic relevance of circulating endothelial progenitor cells for severe traumatic brain injury [J]. Brain injury:[BI], 2012,26(3):291-297.
[24]Lavergne M, Vanneaux V, Delmau C, et al. Cord blood-circulating endothelial progenitors for treatment of vascular diseases [J]. Cell proliferation,2011,44 Suppl 1(44-47.
[25]Rocha V, Gluckman E. Clinical use of umbilical cord blood hematopoietic stem cells [J]. Biology of blood and marrow transplantation:journal of the American Society for Blood and Marrow Transplantation,2006,12(1 Suppl 1):34-41.
[26]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood [J]. Blood,2004,104(9):2752-2760.
[27]Bompais H, Chagraoui J, Canron X, et al. Human endothelial cells derived from circulating progenitors display specific functional properties compared with mature vessel wall endothelial cells [J]. Blood,2004,103(7):2577-2584.
[28]Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals [J]. Blood, 2007,109(5):1801-1809.
[29]Baudin B, Bruneel A, Bosselut N, et al. A protocol for isolation and culture of human umbilical vein endothelial cells [J]. Nature protocols, 2007,2(3):481-485.
[30]Schwartz SM, Gajdusek CM, Selden SC,3rd. Vascular wall growth control: The role of the endothelium [J]. Arteriosclerosis,1981,1(2):107-126.
[31]Kunz J, Schreiter B, Schubert B, et al. [experimental investigations on the regeneration of aortic endothelial cells. Automatic and visual evaluation of autoradiograms (author's transl)] [J]. Acta histochemica,1978,61(1):53-63.
[32]Malczak HT, Buck RC. Regeneration of endothelium in rat aorta after local freezing. A scanning electron microscopic study [J]. The American journal of pathology,1977,86(1):133-148.
[33]Schwartz SM, Gajdusek CM, Reidy MA, et al. Maintenance of integrity in aortic endothelium [J]. Federation proceedings,1980,39(9):2618-2625.
[34]Schwartz SM, Stemerman MB, Benditt EP. The aortic intima. Ii. Repair of the aortic lining after mechanical denudation [J]. The American journal of pathology,1975,81(1):15-42.
[35]Caplan BA, Schwartz CJ. Increased endothelial cell turnover in areas of in vivo evans blue uptake in the pig aorta [J]. Atherosclerosis,1973,17(3):401-417.
[36]Haudenschild CC, Schwartz SM. Endothelial regeneration. Ii. Restitution of endothelial continuity [J]. Laboratory investigation; a journal of technical methods and pathology,1979,41(5):407-418.
[37]Taylor RG, Lewis JC. Endothelial cell proliferation and monocyte adhesion to atherosclerotic lesions of white carneau pigeons [J]. The American journal of pathology,1986,125(1):152-160.
[38]Haudenschild C, Studer A. Early interactions between blood cells and severely damaged rabbit aorta [J]. European journal of clinical investigation, 1971,2(1):1-7.
[39]Gupta R, Tongers J, Losordo DW. Human studies of angiogenic gene therapy [J]. Circulation research,2009,105(8):724-736.
[40]Moreno PR, Sanz J, Fuster V. Promoting mechanisms of vascular health: Circulating progenitor cells, angiogenesis, and reverse cholesterol transport [J]. Journal of the American College of Cardiology,2009,53(25):2315-2323.
[41]Pacilli A, Faggioli G, Stella A, et al. An update on therapeutic angiogenesis for peripheral vascular disease [J]. Annals of vascular surgery,2010,24(2):258-268.
[42]Tongers J, Roncalli JG, Losordo DW. Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation [J]. Microvascular research,2010,79(3):200-206.
[43]Sekiguchi H, Ii M, Losordo DW. The relative potency and safety of endothelial progenitor cells and unselected mononuclear cells for recovery from myocardial infarction and ischemia [J]. Journal of cellular physiology, 2009,219(2):235-242.
[44]Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes [J]. The New England journal of medicine, 2005,353(10):999-1007.
[45]Dimmeler S, Zeiher AM. Cell therapy of acute myocardial infarction:Open questions [J]. Cardiology,2009,113(3):155-160.
[46]George JC. Stem cell therapy in acute myocardial infarction:A review of clinical trials [J]. Translational research:the journal of laboratory and clinical medicine,2010,155(1):10-19.
[47]Martin-Rendon E, Brunskill SJ, Hyde CJ, et al. Autologous bone marrow stem cells to treat acute myocardial infarction:A systematic review [J]. European heart journal,2008,29(15):1807-1818.
[48]Urbich C, Heeschen C, Aicher A, et al. Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells [J]. Circulation,2003,108(20):2511-2516.
[49]Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk [J]. The New England journal of medicine,2003,348(7):593-600.
[50]Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization [J]. Proceedings of the National Academy of Sciences of the United States of America, 2000,97(7):3422-3427.
[51]Lopez-Holgado N, Alberca M, Sanchez-Guijo F, et al. Short-term endothelial progenitor cell colonies are composed of monocytes and do not acquire endothelial markers [J]. Cytotherapy,2007,9(1):14-22.
[52]Prokopi M, Pula G, Mayr U, et al. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures [J]. Blood, 2009,114(3):723-732.
[53]Hur J, Yang HM, Yoon CH, et al. Identification of a novel role of t cells in postnatal vasculogenesis:Characterization of endothelial progenitor cell colonies [J]. Circulation,2007,116(15):1671-1682.
[54]Rohde E, Bartmann C, Schallmoser K, et al. Immune cells mimic the morphology of endothelial progenitor colonies in vitro [J]. Stem Cells, 2007,25(7):1746-1752.
[55]Rohde E, Malischnik C, Thaler D, et al. Blood monocytes mimic endothelial progenitor cells [J]. Stem Cells,2006,24(2):357-367.
[56]Rehman J, Li J, Parvathaneni L, et al. Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells [J]. Journal of the American College of Cardiology, 2004,43(12):2314-2318.
[57]Guven H, Shepherd RM, Bach RG, et al. The number of endothelial progenitor cell colonies in the blood is increased in patients with angiographically significant coronary artery disease [J]. Journal of the American College of Cardiology,2006,48(8):1579-1587.
[58]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis [J]. Arteriosclerosis, thrombosis, and vascular biology,2004,24(2):288-293.
[59]Ingram DA, Mead LE, Moore DB, et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells [J]. Blood,2005,105(7):2783-2786.
[60]Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease [J]. Circulation,2001,103(24):2885-2890.
[61]Au P, Daheron LM, Duda DG, et al. Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels [J]. Blood,2008,111(3):1302-1305.
[62]Prater DN, Case J, Ingram DA, et al. Working hypothesis to redefine endothelial progenitor cells [J]. Leukemia,2007,21 (6):1141-1149.
[63]Meneveau N, Deschaseaux F, Seronde MF, et al. Presence of endothelial colony-forming cells is associated with reduced microvascular obstruction limiting infarct size and left ventricular remodelling in patients with acute myocardial infarction [J]. Basic research in cardiology,2011,106(6):1397-1410.
[64]Wang CH, Hsieh IC, Su Pang JH, et al. Factors associated with purity, biological function, and activation potential of endothelial colony-forming cells [J]. American journal of physiology Regulatory, integrative and comparative physiology,2011,300(3):R586-594.
[65]Shelley WC, Leapley AC, Huang L, et al. Changes in the frequency and in vivo vessel-forming ability of rhesus monkey circulating endothelial colony-forming cells across the lifespan (birth to aged) [J]. Pediatric research, 2012,71(2):156-161.
[66]Kogler G, Critser P, Trapp T, et al. Future of cord blood for non-oncology uses [J]. Bone marrow transplantation,2009,44(10):683-697.
[67]Ladhoff J, Fleischer B, Hara Y, et al. Immune privilege of endothelial cells differentiated from endothelial progenitor cells [J]. Cardiovascular research, 2010,88(1):121-129.
[68]Aghi M, Chiocca EA. Contribution of bone marrow-derived cells to blood vessels in ischemic tissues and tumors [J]. Molecular therapy:the journal of the American Society of Gene Therapy,2005,12(6):994-1005.
[69]Moore XL, Lu J, Sun L, et al. Endothelial progenitor cells' "homing" specificity to brain tumors [J]. Gene Ther,2004,11(10):811-818.
[70]Greve MW, Zink BJ. Pathophysiology of traumatic brain injury [J]. The Mount Sinai journal of medicine, New York,2009,76(2):97-104.
[71]Narayan RK, Michel ME, Ansell B, et al. Clinical trials in head injury [J]. J Neurotrauma,2002,19(5):503-557.
[72]Tolias CM, Bullock MR. Critical appraisal of neuroprotection trials in head injury:What have we learned? [J]. NeuroRx:the journal of the American Society for Experimental NeuroTherapeutics,2004,1 (1):71-79.
[73]Jain KK. Neuroprotection in traumatic brain injury [J]. Drug discovery today, 2008,13(23-24):1082-1089.
[74]Weintraub MI. Thrombolysis (tissue plasminogen activator) in stroke:A medicolegal quagmire [J]. Stroke; a journal of cerebral circulation, 2006,37(7):1917-1922.
[75]Hagg T. From neurotransmitters to neurotrophic factors to neurogenesis [J]. The Neuroscientist:a review journal bringing neurobiology, neurology and psychiatry,2009,15(1):20-27.
[76]Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis [J]. Cell,2008,132(4):645-660.
[77]Taupin P. The therapeutic potential of adult neural stem cells [J]. Current opinion in molecular therapeutics,2006,8(3):225-231.
[78]Greenberg DA, Jin K. From angiogenesis to neuropathology [J]. Nature, 2005,438(7070):954-959.
[79]Ramaswamy S, Goings GE, Soderstrom KE, et al. Cellular proliferation and migration following a controlled cortical impact in the mouse [J]. Brain Res, 2005,1053(1-2):38-53.
[80]Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke [J]. Nature medicine, 2002,8(9):963-970.
[81]Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors [J]. Cell,2002,110(4):429-441.
[82]Kernie SG, Erwin TM, Parada LF. Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice [J]. J Neurosci Res,2001,66(3):317-326.
[83]Lu D, Mahmood A, Qu C, et al. Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury [J]. J Neurotrauma, 2005,22(9):1011-1017.
[84]Xiong Y, Lu D, Qu C, et al. Effects of erythropoietin on reducing brain damage and improving functional outcome after traumatic brain injury in mice [J]. J Neurosurg,2008,109(3):510-521.
[85]Urrea C, Castellanos DA, Sagen J, et al. Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat [J]. Restorative neurology and neuroscience,2007,25(1):65-76.
[86]Zhang R, Zhang L, Zhang Z, et al. A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats [J]. Ann Neurol, 2001,50(5):602-611.
[87]Kadam SD, Mulholland JD, McDonald JW, et al. Neurogenesis and neuronal commitment following ischemia in a new mouse model for neonatal stroke [J]. Brain Res,2008,1208(35-45.
[88]Beck H, Plate KH. Angiogenesis after cerebral ischemia [J]. Acta neuropathologica,2009,117(5):481-496.
[89]Zhang R, Wang L, Zhang L, et al. Nitric oxide enhances angiogenesis via the synthesis of vascular endothelial growth factor and cgmp after stroke in the rat [J]. Circulation research,2003,92(3):308-313.
[90]Morgan R, Kreipke CW, Roberts G, et al. Neovascularization following traumatic brain injury:Possible evidence for both angiogenesis and vasculogenesis [J]. Neurological research,2007,29(4):375-381.
[91]Guo X, Liu L, Zhang M, et al. Correlation of cd34+ cells with tissue angiogenesis after traumatic brain injury in a rat model [J]. J Neurotrauma, 2009,26(8):1337-1344.
[92]Zhang ZG, Zhang L, Jiang Q, et al. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse [J]. Circulation research,2002,90(3):284-288.
[93]Zhang ZG, Chopp M. Neurorestorative therapies for stroke:Underlying mechanisms and translation to the clinic [J]. Lancet neurology, 2009,8(5):491-500.
[94]Li Y, Chopp M. Marrow stromal cell transplantation in stroke and traumatic brain injury [J]. Neuroscience letters,2009,456(3):120-123.
[95]Chopp M, Li Y, Zhang J. Plasticity and remodeling of brain [J]. Journal of the neurological sciences,2008,265(1-2):97-101.
[96]Chopp M, Zhang ZG, Jiang Q. Neurogenesis, angiogenesis, and mri indices of functional recovery from stroke [J]. Stroke; a journal of cerebral circulation, 2007,38(2 Suppl):827-831.
[97]Wu H, Lu D, Jiang H, et al. Simvastatin-mediated upregulation of vegf and bdnf, activation of the pi3k/akt pathway, and increase of neurogenesis are associated with therapeutic improvement after traumatic brain injury [J]. J Neurotrauma,2008,25(2):130-139.
[98]Chen J, Zhang ZG, Li Y, et al. Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke [J]. Ann Neurol,2003,53(6):743-751.
[99]Zhang Y, Xiong Y, Mahmood A, et al. Therapeutic effects of erythropoietin on histological and functional outcomes following traumatic brain injury in rats are independent of hematocrit [J]. Brain Res,2009,1294(153-164.
[100]Arai K, Jin G, Navaratna D, et al. Brain angiogenesis in developmental and pathological processes:Neurovascular injury and angiogenic recovery after stroke [J]. The FEBS journal,2009,276(17):4644-4652.
[101]Pereira AC, Huddleston DE, Brickman AM, et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus [J]. Proceedings of the National Academy of Sciences of the United States of America, 2007,104(13):5638-5643.
[102]Palmer TD, Schwartz PH, Taupin P, et al. Cell culture. Progenitor cells from human brain after death [J]. Nature,2001,411(6833):42-43.
[103]Sanai N, Tramontin AD, Quinones-Hinojosa A, et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration [J]. Nature,2004,427(6976):740-744.
[104]Miljan EA, Sinden JD. Stem cell treatment of ischemic brain injury [J]. Current opinion in molecular therapeutics,2009,11(4):394-403.
[105]Richardson RM, Singh A, Sun D, et al. Stem cell biology in traumatic brain injury:Effects of injury and strategies for repair [J]. J Neurosurg, 2010,112(5):1125-1138.
[106]Torrente Y, Polli E. Mesenchymal stem cell transplantation for neurodegenerative diseases [J]. Cell transplantation,2008,17(10-11):1103-1113.
[107]Kode JA, Mukherjee S, Joglekar MV, et al. Mesenchymal stem cells: Immunobiology and role in immunomodulation and tissue regeneration [J]. Cytotherapy,2009,11(4):377-391.
[108]Fan Y, Shen F, Frenzel T, et al. Endothelial progenitor cell transplantation improves long-term stroke outcome in mice [J]. Ann Neurol, 2010,67(4):488-497.
[109]Moubarik C, Guillet B, Youssef B, et al. Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke [J]. Stem cell reviews,2011,7(1):208-220.
[110]Chen J, Sanberg PR, Li Y, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats [J]. Stroke; a journal of cerebral circulation,2001,32(11):2682-2688.
[111]Ning R, Xiong Y, Mahmood A, et al. Erythropoietin promotes neurovascular remodeling and long-term functional recovery in rats following traumatic brain injury [J]. Brain Res,2011,1384(140-150.
[112]Xiong Y, Mahmood A, Meng Y, et al. Treatment of traumatic brain injury with thymosin beta(4) in rats [J]. J Neurosurg,2011,114(1):102-115.
[113]Chen J, Li Y, Wang L, et al. Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats [J]. Journal of the neurological sciences,2001,189(1-2):49-57.
[114]Li Y, Chen J, Wang L, et al. Treatment of stroke in rat with intracarotid administration of marrow stromal cells [J]. Neurology,2001,56(12):1666-1672.
[115]Newcomb JD, Ajmo CT, Jr., Sanberg CD, et al. Timing of cord blood treatment after experimental stroke determines therapeutic efficacy [J]. Cell transplantation,2006,15(3):213-223.
[116]Critser PJ, Yoder MC. Endothelial colony-forming cell role in neoangiogenesis and tissue repair [J]. Current opinion in organ transplantation, 2010,15(1):68-72.
[117]Ito H, Rovira, II, Bloom ML, et al. Endothelial progenitor cells as putative targets for angiostatin [J]. Cancer research,1999,59(23):5875-5877.
[118]Timmermans F, Van Hauwermeiren F, De Smedt M, et al. Endothelial outgrowth cells are not derived from cdl33+ cells or cd45+ hematopoietic precursors [J]. Arteriosclerosis, thrombosis, and vascular biology, 2007,27(7):1572-1579.
[119]Gunsilius E, Duba HC, Petzer AL, et al. Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells [J]. Lancet,2000,355(9216):1688-1691.
[120]Asosingh K, Aldred MA, Vasanji A, et al. Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension [J]. The American journal of pathology,2008,172(3):615-627.
[121]Yoon CH, Hur J, Park KW, et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells:The role of angiogenic cytokines and matrix metalloproteinases [J]. Circulation,2005,112(11):1618-1627.
[122]Hirschi KK, Ingram DA, Yoder MC. Assessing identity, phenotype, and fate of endothelial progenitor cells [J]. Arteriosclerosis, thrombosis, and vascular biology,2008,28(9):1584-1595.
[123]Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease [J]. Circulation research,2001,89(1):E1-7.
[124]Dimmeler S, Aicher A, Vasa M, et al. Hmg-coa reductase inhibitors (statins) increase endothelial progenitor cells via the pi 3-kinase/akt pathway [J]. The Journal of clinical investigation,2001,108(3):391-397.
[125]Rehman J, Li J, Orschell CM, et al. Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors [J]. Circulation,2003,107(8):1164-1169.
[126]Sieveking DP, Buckle A, Celermajer DS, et al. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations:Insights from a novel human angiogenesis assay [J]. Journal of the American College of Cardiology, 2008,51(6):660-668.
[127]Lin Y, Weisdorf DJ, Solovey A, et al. Origins of circulating endothelial cells and endothelial outgrowth from blood [J]. The Journal of clinical investigation, 2000,105(1):71-77.
[128]Lu D, Goussev A, Chen J, et al. Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury [J]. J Neurotrauma,2004,21(1):21-32.
[129]Dixon CE, Kochanek PM, Yan HQ, et al. One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats [J]. J Neurotrauma,1999,16(2):109-122.
[130]Morris R. Developments of a water-maze procedure for studying spatial learning in the rat [J]. Journal of neuroscience methods,1984,11(1):47-60.
[131]Vorhees CV, Williams MT. Morris water maze:Procedures for assessing spatial and related forms of learning and memory [J]. Nature protocols, 2006,1(2):848-858.
[132]Zhang L, Yang R, Han ZC. Transplantation of umbilical cord blood-derived endothelial progenitor cells:A promising method of therapeutic revascularisation [J]. European journal of haematology,2006,76(1):1-8.
[133]Corselli M, Parodi A, Mogni M, et al. Clinical scale ex vivo expansion of cord blood-derived outgrowth endothelial progenitor cells is associated with high incidence of karyotype aberrations [J]. Experimental hematology, 2008,36(3):340-349.
[134]Aicher A, Brenner W, Zuhayra M, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling [J]. Circulation,2003,107(16):2134-2139.
[135]Schwarz TM, Leicht SF, Radic T, et al. Vascular incorporation of endothelial colony-forming cells is essential for functional recovery of murine ischemic tissue following cell therapy [J]. Arteriosclerosis, thrombosis, and vascular biology,2012,32(2):e13-21.
[136]Chavakis E, Urbich C, Dimmeler S. Homing and engraftment of progenitor cells:A prerequisite for cell therapy [J]. Journal of molecular and cellular cardiology,2008,45(4):514-522.
[137]Bechara C, Chai H, Lin PH, et al. Growth related oncogene-alpha (gro-alpha): Roles in atherosclerosis, angiogenesis and other inflammatory conditions [J]. Medical science monitor:international medical journal of experimental and clinical research,2007,13(6):RA87-90.
[138]Krupinski J, Issa R, Bujny T, et al. A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans [J]. Stroke; a journal of cerebral circulation,1997,28(3):564-573.
[139]Liu XS, Zhang ZG, Zhang RL, et al. Chemokine ligand 2 (ccl2) induces migration and differentiation of subventricular zone cells after stroke [J]. J Neurosci Res,2007,85(10):2120-2125.
[140]Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia [J]. Neuroscience, 2009,158(3):983-994.
[141]Sun D, Bullock MR, Altememi N, et al. The effect of epidermal growth factor in the injured brain after trauma in rats [J]. J Neurotrauma,2010,27(5):923-938.
[142]Zampetaki A, Kirton JP, Xu Q. Vascular repair by endothelial progenitor cells [J]. Cardiovascular research,2008,78(3):413-421.
[143]Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells.1989 [J]. Biochemical and biophysical research communications,2012,425(3):540-547.
[144]Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen [J]. Science,1989,246(4935):1306-1309.
[145]Plouet J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by att-20 cells [J]. The EMBO journal,1989,8(12):3801-3806.
[146]Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-b-cell growth-stimulating factor [J]. Proceedings of the National Academy of Sciences of the United States of America,1994,91(6):2305-2309.
[147]Aiuti A, Webb IJ, Bleul C, et al. 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]. The Journal of experimental medicine,1997,185(1):111-120.
[148]Peled A. Multiple constraint organization in the brain:A theory for schizophrenia [J]. Brain research bulletin,1999,49(4):245-250.
[149]Burns JM, Summers BC, Wang Y, et al. A novel chemokine receptor for sdf-1 and i-tac involved in cell survival, cell adhesion, and tumor development [J]. The Journal of experimental medicine,2006,203(9):2201-2213.
[150]Floege J, Smeets B, Moeller MJ. The sdf-1/cxcr4 axis is a novel driver of vascular development of the glomerulus [J]. Journal of the American Society of Nephrology:JASN,2009,20(8):1659-1661.
[151]Lazarini F, Tham TN, Casanova P, et al. Role of the alpha-chemokine stromal cell-derived factor (sdf-1) in the developing and mature central nervous system [J]. Glia,2003,42(2):139-148.
[152]Li M, Ransohoff RM. Multiple roles of chemokine cxcl12 in the central nervous system:A migration from immunology to neurobiology [J]. Progress in neurobiology,2008,84(2):116-131.
[153]Barresi V, Cerasoli S, Vitarelli E, et al. Density of microvessels positive for cd105 (endoglin) is related to prognosis in meningiomas [J]. Acta neuropathologica,2007,114(2):147-156.
[154]Shweiki D, Itin A, Soffer D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis [J]. Nature, 1992,359(6398):843-845.
[155]Millauer B, Wizigmann-Voos S, Schnurch H, et al. High affinity vegf binding and developmental expression suggest flk-1 as a major regulator of vasculogenesis and angiogenesis [J]. Cell,1993,72(6):835-846.
[156]Deng YB, Ye WB, Hu ZZ, et al. Intravenously administered bmscs reduce neuronal apoptosis and promote neuronal proliferation through the release of vegf after stroke in rats [J]. Neurological research,2010,32(2):148-156.
[157]Mouw G, Zechel JL, Zhou Y, et al. Caspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia [J]. Metabolic brain disease,2002,17(3):143-151.
[158]Hill WD, Hess DC, Martin-Studdard A, et al. Sdf-1 (cxcll2) is upregulated in the ischemic penumbra following stroke:Association with bone marrow cell homing to injury [J]. Journal of neuropathology and experimental neurology, 2004,63(1):84-96.
[159]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 [J]. Circulation,2003,107(9):1322-1328.
[160]Abbott JD, Huang Y, Liu D, et al. Stromal cell-derived factor-lalpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury [J]. Circulation, 2004,110(21):3300-3305.
[161]Tachibana K, Hirota S, Iizasa H, et al. The chemokine receptor cxcr4 is essential for vascularization of the gastrointestinal tract [J]. Nature, 1998,393(6685):591-594.
[162]Salvucci O, Yao L, Villalba S, et al. Regulation of endothelial cell branching morphogenesis by endogenous chemokine stromal-derived factor-1 [J]. Blood, 2002,99(8):2703-2711.
[163]Huo Y, Schober A, Forlow SB, et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein e [J]. Nature medicine, 2003,9(1):61-67.
[164]Yu X, Chen D, Zhang Y, et al. Overexpression of cxcr4 in mesenchymal stem cells promotes migration, neuroprotection and angiogenesis in a rat model of stroke [J]. Journal of the neurological sciences,2012,316(1-2):141-149.
[165]Grant MB, May WS, Caballero S, et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization [J]. Nature medicine,2002,8(6):607-612.
[166]Sheu ML, Cheng FC, Su HL, et al. Recruitment by sdf-1alpha of cd34-positive cells involved in sciatic nerve regeneration [J]. J Neurosurg, 2012,116(2):432-444.
[167]Zou YR, Kottmann AH, Kuroda M, et al. Function of the chemokine receptor cxcr4 in haematopoiesis and in cerebellar development [J]. Nature, 1998,393(6685):595-599.
[168]Peng H, Huang Y, Rose J, et al. Stromal cell-derived factor 1-mediated cxcr4 signaling in rat and human cortical neural progenitor cells [J]. J Neurosci Res, 2004,76(1):35-50.
[169]Itoh T, Satou T, Nishida S, et al. Expression of amyloid precursor protein after rat traumatic brain injury [J]. Neurological research,2009,31(1):103-109.
[170]Amantea D, Nappi G, Bernardi G, et al. Post-ischemic brain damage: Pathophysiology and role of inflammatory mediators [J]. The FEBS journal, 2009,276(1):13-26.
[171]Liu XS, Chopp M, Santra M, et al. Functional response to sdfl alpha through over-expression of cxcr4 on adult subventricular zone progenitor cells [J]. Brain Res,2008,1226(18-26.
[172]Li Y, McIntosh K, Chen J, et al. Allogeneic bone marrow stromal cells promote glial-axonal remodeling without immunologic sensitization after stroke in rats [J]. Exp Neurol,2006,198(2):313-325.
[173]Koch KC, Schaefer WM, Liehn EA, et al. Effect of catheter-based transendocardial delivery of stromal cell-derived factor lalpha on left ventricular function and perfusion in a porcine model of myocardial infarction [J]. Basic research in cardiology,2006,101(1):69-77.
[174]Zheng H, Dai T, Zhou B, et al. Sdf-lalpha/cxcr4 decreases endothelial progenitor cells apoptosis under serum deprivation by pi3k/akt/enos pathway [J]. Atherosclerosis,2008,201(1):36-42.
[1]Schwartz SM, Gajdusek CM, Selden SC,3rd. Vascular wall growth control:The role of the endothelium [J]. Arteriosclerosis,1981,1(2):107-126.
[2]Schwartz SM, Stemerman MB, Benditt EP. The aortic intima. Ii. Repair of the aortic lining after mechanical denudation [J]. The American journal of pathology, 1975,81(1):15-42.
[3]Schwartz SM, Gajdusek CM, Reidy MA, et al. Maintenance of integrity in aortic endothelium [J]. Federation proceedings,1980,39(9):2618-2625.
[4]Malczak HT, Buck RC. Regeneration of endothelium in rat aorta after local freezing. A scanning electron microscopic study [J]. The American journal of pathology,1977,86(1):133-148.
[5]Kunz J, Schreiter B, Schubert B, et al. [experimental investigations on the regeneration of aortic endothelial cells. Automatic and visual evaluation of autoradiograms (author's transl)] [J]. Acta histochemica,1978,61(1):53-63.
[6]Caplan BA, Schwartz CJ. Increased endothelial cell turnover in areas of in vivo evans blue uptake in the pig aorta [J]. Atherosclerosis,1973,17(3):401-417.
[7]Haudenschild C, Studer A. Early interactions between blood cells and severely damaged rabbit aorta [J]. European journal of clinical investigation, 1971,2(1):1-7.
[8]Haudenschild CC, Schwartz SM. Endothelial regeneration. Ii. Restitution of endothelial continuity [J]. Laboratory investigation; a journal of technical methods and pathology,1979,41(5):407-418.
[9]Taylor RG, Lewis JC. Endothelial cell proliferation and monocyte adhesion to atherosclerotic lesions of white carneau pigeons [J]. The American journal of pathology,1986,125(1):152-160.
[10]Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis [J]. Science,1997,275(5302):964-967.
[11]Gupta R, Tongers J, Losordo DW. Human studies of angiogenic gene therapy [J]. Circulation research,2009,105(8):724-736.
[12]Moreno PR, Sanz J, Fuster V. Promoting mechanisms of vascular health: Circulating progenitor cells, angiogenesis, and reverse cholesterol transport [J]. Journal of the American College of Cardiology,2009,53(25):2315-2323.
[13]Pacilli A, Faggioli G, Stella A, et al. An update on therapeutic angiogenesis for peripheral vascular disease [J]. Annals of vascular surgery,2010,24(2):258-268.
[14]Tongers J, Roncalli JG, Losordo DW. Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation [J]. Micro vascular research,2010,79(3):200-206.
[15]Sekiguchi H, li M, Losordo DW. The relative potency and safety of endothelial progenitor cells and unselected mononuclear cells for recovery from myocardial infarction and ischemia [J]. Journal of cellular physiology,2009,219(2):235-242.
[16]Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes [J]. The New England journal of medicine, 2005,353(10):999-1007.
[17]Zeoli A, Dentelli P, Brizzi MF. Endothelial progenitor cells and their potential clinical implication in cardiovascular disorders [J]. Journal of endocrinological investigation,2009,32(4):370-382.
[18]Jujo K, Li M, Losordo DW. Endothelial progenitor cells in neovascularization of infarcted myocardium [J]. Journal of molecular and cellular cardiology, 2008,45(4):530-544.
[19]Dimmeler S, Zeiher AM. Cell therapy of acute myocardial infarction:Open questions [J]. Cardiology,2009,113(3):155-160.
[20]George JC. Stem cell therapy in acute myocardial infarction:A review of clinical trials [J]. Translational research:the journal of laboratory and clinical medicine, 2010,155(1):10-19.
[21]Martin-Rendon E, Brunskill SJ, Hyde CJ, et al. Autologous bone marrow stem cells to treat acute myocardial infarction:A systematic review [J]. European heart journal,2008,29(15):1807-1818.
[22]Steinmetz M, Nickenig G, Werner N. Endothelial-regenerating cells:An expanding universe [J]. Hypertension,2010,55(3):593-599.
[23]Yoder MC, Ingram DA. Endothelial progenitor cell:Ongoing controversy for defining these cells and their role in neoangiogenesis in the murine system [J]. Current opinion in hematology,2009,16(4):269-273.
[24]Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization [J]. Proceedings of the National Academy of Sciences of the United States of America, 2000,97(7):3422-3427.
[25]Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization [J]. Nature medicine,1999,5(4):434-438.
[26]Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease [J]. Circulation research,2001,89(1):El-7.
[27]Assmus B, Rolf A, Erbs S, et al. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction [J]. Circulation Heart failure,2010,3(1):89-96.
[28]Chavakis E, Urbich C, Dimmeler S. Homing and engraftment of progenitor cells: A prerequisite for cell therapy [J]. Journal of molecular and cellular cardiology, 2008,45(4):514-522.
[29]Kovacic JC, Harvey RP, Dimmeler S. Cardiovascular regenerative medicine: Digging in for the long haul [J]. Cell stem cell,2007,1(6):628-633.
[30]Urbich C, Rossig L, Dimmeler S. Restoration of cardiac function with progenitor cells [J]. Novartis Foundation symposium,2006,274(214-223; discussion 223-217,272-216.
[31]Abdul-Salam F, Mansour MH, Al-Shemary T. The selective expression of distinct fucosylated glycoproteins on murine t and b lymphocyte subsets [J]. Immunobiology,2005,210(9):695-708.
[32]Baldus SE, Thiele J, Charles A, et al. Carbohydrate antigens of human megakaryocytes and platelet glycoproteins:A comparative study [J]. Histochemistry,1994,102(3):205-211.
[33]Chionh YT, Wee JL, Every AL, et al. M-cell targeting of whole killed bacteria induces protective immunity against gastrointestinal pathogens [J]. Infection and immunity,2009,77(7):2962-2970.
[34]Gao X, Chen J, Tao W, et al. Uea i-bearing nanoparticles for brain delivery following intranasal administration [J]. International journal of pharmaceutics, 2007,340(1-2):207-215.
[35]Georgiou S, Pasmatzi E, Monastirli A, et al. Age-related alterations in the carbohydrate residue composition of the cell surface in the unexposed normal human epidermis [J]. Gerontology,2005,51 (3):155-160.
[36]Kobayashi N, Matsuzaki O, Shirai S, et al. Collecting duct carcinoma of the kidney:An immunohistochemical evaluation of the use of antibodies for differential diagnosis [J]. Human pathology,2008,39(9):1350-1359.
[37]Schmitz B, Thiele J, Otto F, et al. Interactions between endogeneous lectins and fucosylated oligosaccharides in megakaryocyte-dependent fibroblast growth of the normal bone marrow [J]. Leukemia,1996,10(10):1604-1614.
[38]Thom I, Schult-Kronefeld O, Burkholder I, et al. Lectin histochemistry of metastatic adenocarcinomas of the lung [J]. Lung Cancer,2007,56(3):391-397.
[39]Zhang SJ, Zhang H, Wei YJ, et al. Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture [J]. Cell research,2006,16(6):577-584.
[40]Prokopi M, Pula G, Mayr U, et al. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures [J]. Blood, 2009,114(3):723-732.
[41]Hassan NF, Campbell DE, Douglas SD. Purification of human monocytes on gelatin-coated surfaces [J]. Journal of immunological methods, 1986,95(2):273-276.
[42]Schmeisser A, Garlichs CD, Zhang H, et al. Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in matrigel under angiogenic conditions [J]. Cardiovascular research,2001,49(3):671-680.
[43]Schmeisser A, Graffy C, Daniel WG, et al. Phenotypic overlap between monocytes and vascular endothelial cells [J]. Advances in experimental medicine and biology,2003,522(59-74.
[44]Medina RJ, O'Neill CL, Sweeney M, et al. Molecular analysis of endothelial progenitor cell (epc) subtypes reveals two distinct cell populations with different identities [J]. BMC medical genomics,2010,3(18.
[45]Peichev M, Naiyer AJ, Pereira D, et al. Expression of vegfr-2 and acl33 by circulating human cd34(+) cells identifies a population of functional endothelial precursors [J]. Blood,2000,95(3):952-958.
[46]Bertolini F, Mancuso P, Braidotti P, et al. The multiple personality disorder phenotype(s) of circulating endothelial cells in cancer [J]. Biochimica et biophysica acta,2009,1796(1):27-32.
[47]Case J, Mead LE, Bessler WK, et al. Human cd34+acl33+vegfr-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors [J]. Experimental hematology,2007,35(7):1109-1118.
[48]Estes ML, Mund JA, Ingram DA, et al. Identification of endothelial cells and progenitor cell subsets in human peripheral blood [J]. Current protocols in cytometry/editorial board, J Paul Robinson, managing editor [et al], 2010,Chapter 9(Unit 9 33 31-11.
[49]Timmermans F, Van Hauwermeiren F, De Smedt M, et al. Endothelial outgrowth cells are not derived from cdl33+ cells or cd45+ hematopoietic precursors [J]. Arteriosclerosis, thrombosis, and vascular biology,2007,27(7):1572-1579.
[50]Bertolini F, Mancuso P, Kerbel RS. Circulating endothelial progenitor cells [J]. The New England journal of medicine,2005,353(24):2613-2616; author reply 2613-2616.
[51]Gao D, Nolan DJ, Mellick AS, et al. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis [J]. Science, 2008,319(5860):195-198.
[52]Nolan DJ, Ciarrocchi A, Mellick AS, et al. Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization [J]. Genes & development,2007,21(12):1546-1558.
[53]Hagensen MK, Shim J, Thim T, et al. Circulating endothelial progenitor cells do not contribute to plaque endothelium in murine atherosclerosis [J]. Circulation, 2010,121(7):898-905.
[54]Perry TE, Song M, Despres DJ, et al. Bone marrow-derived cells do not repair endothelium in a mouse model of chronic endothelial cell dysfunction [J]. Cardiovascular research,2009,84(2):317-325.
[55]Purhonen S, Palm J, Rossi D, et al. Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth [J]. Proceedings of the National Academy of Sciences of the United States of America,2008,105(18):6620-6625.
[56]Aicher A, Rentsch M, Sasaki K, et al. Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia [J]. Circulation research,2007,100(4):581-589.
[57]Hillebrands JL, Klatter FA, van Dijk WD, et al. Bone marrow does not contribute substantially to endothelial-cell replacement in transplant arteriosclerosis [J]. Nature medicine,2002,8(3):194-195.
[58]Estes ML, Mund JA, Mead LE, et al. Application of polychromatic flow cytometry to identify novel subsets of circulating cells with angiogenic potential [J]. Cytometry Part A:the journal of the International Society for Analytical Cytology,2010,77(9):831-839.
[59]Ito H, Miyake M, Nishitani E, et al. Anti-tumor promoting activity of polyphenols from cowania mexicana and coleogyne ramosissima [J]. Cancer letters,1999,143(1):5-13.
[60]Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk [J]. The New England journal of medicine,2003,348(7):593-600.
[61]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood [J]. Blood,2004,104(9):2752-2760.
[62]Lin Y, Weisdorf DJ, Solovey A, et al. Origins of circulating endothelial cells and endothelial outgrowth from blood [J]. The Journal of clinical investigation, 2000,105(1):71-77.
[63]Ingram DA, Mead LE, Moore DB, et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells [J]. Blood,2005,105(7):2783-2786.
[64]Au P, Daheron LM, Duda DG, et al. Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels [J]. Blood,2008,111 (3):1302-1305.
[65]Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals [J]. Blood, 2007,109(5):1801-1809.
[66]Melero-Martin JM, Khan ZA, Picard A, et al. In vivo vasculogenic potential of human blood-derived endothelial progenitor cells [J]. Blood, 2007,109(11):4761-4768.
[67]Rohde E, Bartmann C, Schallmoser K, et al. Immune cells mimic the morphology of endothelial progenitor colonies in vitro [J]. Stem Cells, 2007,25(7):1746-1752.
[68]Rohde E, Malischnik C, Thaler D, et al. Blood monocytes mimic endothelial progenitor cells [J]. Stem Cells,2006,24(2):357-367.
[69]Sieveking DP, Buckle A, Celermajer DS, et al. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations:Insights from a novel human angiogenesis assay [J]. Journal of the American College of Cardiology, 2008,51(6):660-668.
[70]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis [J]. Arteriosclerosis, thrombosis, and vascular biology,2004,24(2):288-293.
[71]Mukai N, Akahori T, Komaki M, et al. A comparison of the tube forming potentials of early and late endothelial progenitor cells [J]. Experimental cell research,2008,314(3):430-440.
[72]Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J]. Circulation research,1999,85(3):221-228.
[73]Zhang ZG, Zhang L, Jiang Q, et al. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse [J]. Circulation research,2002,90(3):284-288.
[74]Gill M, Dias S, Hattori K, et al. Vascular trauma induces rapid but transient mobilization of vegfr2(+)acl33(+) endothelial precursor cells [J]. Circulation research,2001,88(2):167-174.
[75]Shintani S, Murohara T, Ikeda H, et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction [J]. Circulation, 2001,103(23):2776-2779.
[76]Walter DH, Rittig K, Bahlmann FH, et al. Statin therapy accelerates reendothelialization:A novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells [J]. Circulation, 2002,105(25):3017-3024.
[77]Kalka C, Masuda H, Takahashi T, et al. Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects [J]. Circulation research,2000,86(12):1198-1202.
[78]Hamano K, Li TS, Kobayashi T, et al. Therapeutic angiogenesis induced by local autologous bone marrow cell implantation [J]. The Annals of thoracic surgery, 2002,73(4):1210-1215.
[79]Kamihata H, Matsubara H, Nishiue T, et al. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines [J]. Circulation,2001,104(9):1046-1052.
[80]Isner JM, Asahara T. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization [J]. The Journal of clinical investigation, 1999,103(9):1231-1236.
[81]Murohara T, Ikeda H, Duan J, et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization [J]. The Journal of clinical investigation,2000,105(11):1527-1536.
[82]Kawamoto A, Gwon HC, Iwaguro H, et al. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia [J]. Circulation, 2001,103(5):634-637.
[83]Iwaguro H, Yamaguchi J, Kalka C, et al. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration [J]. Circulation, 2002,105(6):732-738.
[84]Murasawa S, Llevadot J, Silver M, et al. Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells [J]. Circulation,2002,106(9):1133-1139.
[85]Pucci F, Venneri MA, Biziato D, et al. A distinguishing gene signature shared by tumor-infiltrating tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships [J]. Blood,2009,114(4):901-914.
[86]Coffelt SB, Lewis CE, Naldini L, et al. Elusive identities and overlapping phenotypes of proangiogenic myeloid cells in tumors [J]. The American journal of pathology,2010,176(4):1564-1576.
[87]Fantin A, Vieira JM, Gestri G, et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of vegf-mediated endothelial tip cell induction [J]. Blood,2010,116(5):829-840.
[88]Dubois C, Liu X, Claus P, et al. Differential effects of progenitor cell populations on left ventricular remodeling and myocardial neovascularization after myocardial infarction [J]. Journal of the American College of Cardiology, 2010,55(20):2232-2243.
[89]Medina RJ, O'Neill CL, Humphreys MW, et al. Outgrowth endothelial cells: Characterization and their potential for reversing ischemic retinopathy [J]. Investigative ophthalmology & visual science,2010,51(11):5906-5913.