重组人粒细胞集落刺激因子动员内皮祖细胞对脑创伤大鼠功能恢复的影响
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摘要
[目的]
内皮祖细胞(endothelial progenitor cells, EPCs)不仅维持正常脉管系统的生理功能,而且主导病理状态下的血管再生与修复。但目前对于颅脑创伤后的血管生成研究尚不多见。重组人粒细胞集落刺激因子(granulocyte colony stimulating factor, rhG-CSF)具有动员骨髓内皮祖细胞进入外周血,增殖分化为内皮细胞的前体细胞,参与损伤组织血管的修复和再生的作用。因此rhG-CSF在神经系统病方面的研究成为热门。本实验通过观察rhG-CSF对颅脑创伤(traumatic brain injury, TBI)后对神经功能的保护作用,以期探讨颅脑创伤治疗中的可能新途径。
[材料与方法]
1.健康成年雄性Wistar大鼠36只(体重300-350g,鼠龄7周),随机分为假手术(Sham)组、盐水(NS)组和粒细胞集落刺激因子(rhG-CSF)组,每组12只。TBI模型建立：在颅骨前囟后4.4mm,矢状缝侧方2.4mm钻直径4mm的骨孔,应用大鼠液压打击仪(Fluid-Percussion injury, FPI)以2.0～2.5 atm的打击力度致伤。Sham组只磨骨孔,不打击。rhG-CSF组在打击后3小时内,给予皮下注射rhG-CSF (50μg/kg),每天1次,连续注射5天。NS组于打击后给予等量生理盐水。各组分别于打击后6小时、1天、3天和6天取大鼠内眦球后静脉丛血液约0.5ml,采用Ficoll密度梯度离心法分离大鼠循环血单个核细胞,以CD34、CD133双抗体阳性作为EPCs标志,应用流式细胞仪(flow cytometer, FCM)测定大鼠循环血中EPCs数量。各组分别于TBI后1天、4天、7天、14天和21天进行改良神经功能评分(modified Neurological Severity Score, mNSS)。在TBI后21-25天进行Morris水迷宫(Morris Water Maze, MWM)试验。
2.健康成年雄性Wistar大鼠56只,随机分为NS组和rhG-CSF组,每组28只。TBI后4天、7天、14天和21天,NS组和rhG-CSF组分别随机取7只大鼠,取脑行冰冻切片免疫组化,计数创伤区周围(Boundary Zone, BZ)和海马CA3区的CD31微血管(CD31-MVD)数量。
[结果]
1.大鼠脑创伤后6小时,循环血中CD34/CD133双阳性的EPCs明显超过正常水平,1天以后逐渐回落到正常水平。伤后皮下注射rhG-CSF,可以显著提高大鼠循环血中EPCs数量,随着用药时间的延长,EPCs数量逐渐增多。
2. mNss检测发现,TBI后大鼠神经功能受到严重损害。经rhG-CSF治疗的大鼠,神经功能的改善明显优于NS组(P<0.05)。
3.MWM检测发现,TBI后大鼠空间学习记忆功能障碍。经rhG-CSF治疗的大鼠,空间学习记忆功能明显优于NS组。伤后24、25天rhG-CSF组逃避潜伏期明显比NS组减少(P<0.05),同时象限百分率增高(P<0.05)。
4.TBI后BZ及伤侧海马CA3区,NS组CD31-MVD于伤后7天达到峰值,随后有所下降；应用rhG-CSF后,伤后14、21天BZ及伤侧海马CA3区CD31-MVD明显高于NS组(P<0.05)。[结论]
1.脑创伤后EPCs从骨髓动员入循环血中,rhG-CSF可以显著增加脑创伤后大鼠外周血EPCs的动员。
2.脑创伤使大鼠的神经功能和空间学习记忆能力障碍,rhG-CSF可以明显促进神经功能恢复和改善空间学习记忆能力。
3. rhG-CSF可以通过动员和促进EPCs的归巢,从而增强损伤脑组织的血管再生和促进神经功能的恢复。
Objective:
Endothelial progenitor cells (EPCs) maintain the physiologic functions of normal vascular system; they also play a pivotal role in vasculogenesis and angiogenesis in pathologic condition. However, there is rare study of EPCs related angiogenesis in traumatic brain injury (TBI). Granulocyte colony-stimulating factor (G-CSF) is well-established to mobilize EPCs which proliferate and differentiat precursor cells of endotheliocyte from bone marrow into the peripheral blood, participates repair and regeneration of injure tissues. G-CSF becomes popular in nervous system disease. To investigate the effect of G-CSF on the neurofunctional protection, we hope to find a new way to treat craniocerebral trauma.
Material and Methods:
1.36 of 300-350g and 7 week age adult male Wistar rats (from Academy of Military Medical of China) were randomly divided into three groups:Sham group (12), normal saline group (NS,12) and rhG-CSF group (12). rats were anesthetized with 10% chloral hydrate (0.3ml/kg) administered intraperitoneally and then placed in a stereotaxic frame. A 4.0 mm craniotomy was performed over the right parietal skull to expose the dura (4.4 mm posterior from bregma and 2.4 mm lateral to the sagittal suture). The pressure pulse of the fluid percussion device between 2.0 to 2.5 atm. Sham group grinds the skull but not to percuss. RhG-CSF group was administered G-CSF (50μg/kg; Chugai Pharmaceutical, Co., Japan) subcutaneously for 5 consecutive days after TBI. NS group mitte tales doses normal saline. The 0.5ml blood samples was collected from the rat eyes at 6 hr, 1day,3 day and 6 day after TBI. Blood samples were first subjected to a Ficoll gradient centrifugation to isolate mononuclear cells using a commercial kit. The isolated cells suspended in BSA buffer were incubated with a both PE-conjugated CD34 antibody and FITC-conjugated CD133 antibody for 10 minutes at room temperature. Then the staining cells were analyzed in a flow cytometry. The modified neurological severity score tests were carried out on preinjury and on days 1,4,7,14, and 21 after TBI. The Morris water maze test was tested on days 21-25 after TBI.
2.56 of adult male Wistar rats were randomly divided into NS group and rhG-CSF group,28 rats in each group. CD31-MVD were measured by immunohistochemistry in boundary zone of lesion and the CA3 region of the hippocampus on days 4,7,14 and 21 after TBI. Random 7 rats were divided in each time piont.
Results:
1. There were double CD34/CD133 positive cells, which were defined as EPCs, in the circulating blood in rats. The numbers of circulating EPCs increased significantly at 6 hr after TBI, recurred to normal level after 1 day. After G-CSF mobilization, the numbers of circulating EPCs increased significantly and gradully increased with injection frequency.
2. Injury in the hemisphere cortex of rats causes neurological functional deficits as measured by mNSS. The mNSS scores for the rhG-CSF group were significantly decreased at days 14 and 21 after TBI when compared with the NS group.
3. The dysfunction of spatial learning were found by the Morris water maze test. the rhG-CSF group reduced the dysfunction of spatial learning caused by the brain damage in this model. The percentage of time spent in the correct quadrant was significantly higher and escape latency was significantly lower in the rhG-CSF group than the NS group during the water maze test.
4. CD31-MVD was measured in boundary zone of lesion and the CA3 region of the hippocampus. The number of CD31-MVD was highest at 7 day in the NS group, significantly higher in the rhG-CSF group than the NS group at 7, 14, and 21 days after TBI.
Conclusion:
1. EPCs can be mobilized to the circulating blood from bone marrow after TBI. The numbers of circulating EPCs were increased significantly by G-CSF after TBI.
2. Injury in the hemisphere cortex of rats causes neurological functional deficits and spatial learning disfunction. These disfunctions were recoveried by G-CSF.
3. Circulating EPCs were mobilized and homing by G-CSF. The higher EPCs level conduces to augment more angiogenesis and functional recovery in the injured brain after TBI.
内皮祖细胞(endothelial progenitor cells, EPCs)不仅维持正常脉管系统的生理功能,而且主导病理状态下的血管再生与修复。但目前对于颅脑创伤后的血管生成研究尚不多见。重组人粒细胞集落刺激因子(granulocyte colony stimulating factor, rhG-CSF)具有动员骨髓内皮祖细胞进入外周血,增殖分化为内皮细胞的前体细胞,参与损伤组织血管的修复和再生的作用。因此rhG-CSF在神经系统病方面的研究成为热门。本实验通过观察rhG-CSF对颅脑创伤(traumatic brain injury, TBI)后对神经功能的保护作用,以期探讨颅脑创伤治疗中的可能新途径。
[材料与方法]
1.健康成年雄性Wistar大鼠36只(体重300-350g,鼠龄7周),随机分为假手术(Sham)组、盐水(NS)组和粒细胞集落刺激因子(rhG-CSF)组,每组12只。TBI模型建立：在颅骨前囟后4.4mm,矢状缝侧方2.4mm钻直径4mm的骨孔,应用大鼠液压打击仪(Fluid-Percussion injury, FPI)以2.0～2.5 atm的打击力度致伤。Sham组只磨骨孔,不打击。rhG-CSF组在打击后3小时内,给予皮下注射rhG-CSF (50μg/kg),每天1次,连续注射5天。NS组于打击后给予等量生理盐水。各组分别于打击后6小时、1天、3天和6天取大鼠内眦球后静脉丛血液约0.5ml,采用Ficoll密度梯度离心法分离大鼠循环血单个核细胞,以CD34、CD133双抗体阳性作为EPCs标志,应用流式细胞仪(flow cytometer, FCM)测定大鼠循环血中EPCs数量。各组分别于TBI后1天、4天、7天、14天和21天进行改良神经功能评分(modified Neurological Severity Score, mNSS)。在TBI后21-25天进行Morris水迷宫(Morris Water Maze, MWM)试验。
2.健康成年雄性Wistar大鼠56只,随机分为NS组和rhG-CSF组,每组28只。TBI后4天、7天、14天和21天,NS组和rhG-CSF组分别随机取7只大鼠,取脑行冰冻切片免疫组化,计数创伤区周围(Boundary Zone, BZ)和海马CA3区的CD31微血管(CD31-MVD)数量。
[结果]
1.大鼠脑创伤后6小时,循环血中CD34/CD133双阳性的EPCs明显超过正常水平,1天以后逐渐回落到正常水平。伤后皮下注射rhG-CSF,可以显著提高大鼠循环血中EPCs数量,随着用药时间的延长,EPCs数量逐渐增多。
2. mNss检测发现,TBI后大鼠神经功能受到严重损害。经rhG-CSF治疗的大鼠,神经功能的改善明显优于NS组(P<0.05)。
3.MWM检测发现,TBI后大鼠空间学习记忆功能障碍。经rhG-CSF治疗的大鼠,空间学习记忆功能明显优于NS组。伤后24、25天rhG-CSF组逃避潜伏期明显比NS组减少(P<0.05),同时象限百分率增高(P<0.05)。
4.TBI后BZ及伤侧海马CA3区,NS组CD31-MVD于伤后7天达到峰值,随后有所下降；应用rhG-CSF后,伤后14、21天BZ及伤侧海马CA3区CD31-MVD明显高于NS组(P<0.05)。[结论]
1.脑创伤后EPCs从骨髓动员入循环血中,rhG-CSF可以显著增加脑创伤后大鼠外周血EPCs的动员。
2.脑创伤使大鼠的神经功能和空间学习记忆能力障碍,rhG-CSF可以明显促进神经功能恢复和改善空间学习记忆能力。
3. rhG-CSF可以通过动员和促进EPCs的归巢,从而增强损伤脑组织的血管再生和促进神经功能的恢复。
Objective:
Endothelial progenitor cells (EPCs) maintain the physiologic functions of normal vascular system; they also play a pivotal role in vasculogenesis and angiogenesis in pathologic condition. However, there is rare study of EPCs related angiogenesis in traumatic brain injury (TBI). Granulocyte colony-stimulating factor (G-CSF) is well-established to mobilize EPCs which proliferate and differentiat precursor cells of endotheliocyte from bone marrow into the peripheral blood, participates repair and regeneration of injure tissues. G-CSF becomes popular in nervous system disease. To investigate the effect of G-CSF on the neurofunctional protection, we hope to find a new way to treat craniocerebral trauma.
Material and Methods:
1.36 of 300-350g and 7 week age adult male Wistar rats (from Academy of Military Medical of China) were randomly divided into three groups:Sham group (12), normal saline group (NS,12) and rhG-CSF group (12). rats were anesthetized with 10% chloral hydrate (0.3ml/kg) administered intraperitoneally and then placed in a stereotaxic frame. A 4.0 mm craniotomy was performed over the right parietal skull to expose the dura (4.4 mm posterior from bregma and 2.4 mm lateral to the sagittal suture). The pressure pulse of the fluid percussion device between 2.0 to 2.5 atm. Sham group grinds the skull but not to percuss. RhG-CSF group was administered G-CSF (50μg/kg; Chugai Pharmaceutical, Co., Japan) subcutaneously for 5 consecutive days after TBI. NS group mitte tales doses normal saline. The 0.5ml blood samples was collected from the rat eyes at 6 hr, 1day,3 day and 6 day after TBI. Blood samples were first subjected to a Ficoll gradient centrifugation to isolate mononuclear cells using a commercial kit. The isolated cells suspended in BSA buffer were incubated with a both PE-conjugated CD34 antibody and FITC-conjugated CD133 antibody for 10 minutes at room temperature. Then the staining cells were analyzed in a flow cytometry. The modified neurological severity score tests were carried out on preinjury and on days 1,4,7,14, and 21 after TBI. The Morris water maze test was tested on days 21-25 after TBI.
2.56 of adult male Wistar rats were randomly divided into NS group and rhG-CSF group,28 rats in each group. CD31-MVD were measured by immunohistochemistry in boundary zone of lesion and the CA3 region of the hippocampus on days 4,7,14 and 21 after TBI. Random 7 rats were divided in each time piont.
Results:
1. There were double CD34/CD133 positive cells, which were defined as EPCs, in the circulating blood in rats. The numbers of circulating EPCs increased significantly at 6 hr after TBI, recurred to normal level after 1 day. After G-CSF mobilization, the numbers of circulating EPCs increased significantly and gradully increased with injection frequency.
2. Injury in the hemisphere cortex of rats causes neurological functional deficits as measured by mNSS. The mNSS scores for the rhG-CSF group were significantly decreased at days 14 and 21 after TBI when compared with the NS group.
3. The dysfunction of spatial learning were found by the Morris water maze test. the rhG-CSF group reduced the dysfunction of spatial learning caused by the brain damage in this model. The percentage of time spent in the correct quadrant was significantly higher and escape latency was significantly lower in the rhG-CSF group than the NS group during the water maze test.
4. CD31-MVD was measured in boundary zone of lesion and the CA3 region of the hippocampus. The number of CD31-MVD was highest at 7 day in the NS group, significantly higher in the rhG-CSF group than the NS group at 7, 14, and 21 days after TBI.
Conclusion:
1. EPCs can be mobilized to the circulating blood from bone marrow after TBI. The numbers of circulating EPCs were increased significantly by G-CSF after TBI.
2. Injury in the hemisphere cortex of rats causes neurological functional deficits and spatial learning disfunction. These disfunctions were recoveried by G-CSF.
3. Circulating EPCs were mobilized and homing by G-CSF. The higher EPCs level conduces to augment more angiogenesis and functional recovery in the injured brain after TBI.
引文
[1]Stoffel M, Eriskat J, Plesnila M, et al. The penumbra zone of a traumatic cortical lesion:a microdialysis study of excitatory amino acid release[J]. Acta Neurochir Suppl,1997;70:91-93.
[2]杨树源,安沂华.再述神经干细胞的研究及应用前景[J].中华神经外科杂志,2002；18(5)：273-274.
[3]Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model [J]. J Clin Invest,2004;114:330-338.
[4]Shen Q, Goderie SK, Jin L, et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells [J]. Science, 2004;304(5675):1338-1340.
[5]Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis[J]. Science,1997;275:964-967.
[6]Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors [J]. Blood,2000;95:952-958.
[7]Hill JM, Zalos G. Circulating Endothelial progenitor cells, vascular function, and cardiovascular risk[J]. N Eng J Med,2003;348:593-600.
[8]Walter DH, Rittig K, Bahlmann FH, et al. Statin therapy accelerate reendothelialization:a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells[J]. Circulation,2002; 105:3017-3024.
[9]Murohara T, Ikeda H, Duan J, et al. Transplanted cord blood-derived endothelial progenitor cells augment postnatal neovascularization[J]. J Clin Invest,2000;105:1527-1536.
[10]Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function[J]. Nat Med,2001;7:430-436.
[11]Grant MB, May WS, Caballero S, et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization[J]. Nat Med,2002;8:607-612.
[12]Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cells significance in angiogenic growth factor-induced neovascularization[J]. Exp Hematol, 2002;30:967-972.
[13]Suzuki T, Nishida M, Futami S, et al. Neoendothelialization after peripheral blood stem cell transplantation in humans. A case report of a Tokaimura nuclear accident victim[J]. Cardiovasc Res,2003;58:487-492.
[14]Folkman J, Shing Y. Angiogenesis[J]. J Boil Chem, 1992;267(16):10931-10934.
[15]Risau W, Flamme I. Vasculogenesis[J]. Ann Rev Cell Dev Biol, 1995;11(9):79-91.
[16]Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells[J]. Blood,1998;92:362-367.
[17]Li Liu, Hui Liu,_JunFeng Jiao, et al._Changes in Circulating Human Endothelial Progenitor Cells after Brain Injury[J]. J Neurotrauma, 2007;24(6):936-943.
[18]John Glod, David Kobiler, Martha Noel,_et al. Monocytes form a vascular barrier and participate in vessel repair after brain injury[J].Blood, 2006;107:940-946.
[19]Morgan R, Kreipke CW, Roberts G,_et al._Neovascularization following traumatic brain injury:possible evidence for both angiogenesis and vasculogenesis[J]. Neurol Res,2007;29:375-381.
[20]Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration[J]. Nat Med,2003;9:702-712.
[21]Westenbrink BD, Lipsic E, van der Meer P, et al. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization[J]. Eur Heart J, 2007;28(16):2018-2027.
[22]Powell TM, Paul JD, Hill JM, et al. Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease[J]. Arterioscler Thromb Vasc Biol,2005;25(2):296-301.
[23]Takahashi T, Kalka C, Masuda H, et al. Ischemia and cytokine induced mobilization of bone marrow derived endothelial progenitor cells for neovascularization[J]. Nat Med,1999;5(4):434-438.
[24]Keswani SG, Katz AB, Lim FY, Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type Ⅰ and type Ⅱ diabetic wounds [J]. Wound Repair Regen,2004;12(5):497-504.
[25]Asahara T, Takahashi T, Masuda H, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow derived endothelial progenitor cells[J]. EMBO J,1999; 18(14):3964-3972.
[26]Heeschen C, Aicher A, Lehmann R, et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization[J]. Blood, 2003;102:1340-1346.
[27]Llevadot J, Murasawa S, Kureishi Y, et al. HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells[J]. J Clin Invest,2001;108:399-405.
[28]Iwakura A, Luedemann C, Shastry S, et al. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury[J]. Circulation,2003;108:3115-3121.
[29]Laufs U, Werner N, Link A, et al. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis[J]. Circulation,2004; 109:220-226.
[30]Ohki Y, Heissig B, Sato Y, et al. Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils[J]. FASEB J,2005;19(14):2005-2007.
[31]Honold J, Lehmann R, Heeschen C, et al. Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease[J]. Arterioscler Thromb Vasc Biol,2006;26(10):2238-2243.
[32]Gibson CL, Bath PM, Murphy SP. G-CSF reduces infarct volume and improves functional outcome after transient focal cerebral ischemia in mice[J]. J Cereb Blood Flow Metab,2005;25(4):431-439.
[33]McIntosh TK, Vink R, Noble L, et al. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model [J]. Neuroscience, 1989;28:233-244.
[34]Chen J, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats[J]. Stroke,2001;32(4):1005-1011.
[35]Massa M, Rosti V, Ferrario M, et al._Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction[J]. Blood,2005;105(1):199-206.
[36]Lee DY, Cho TJ, Kim JA, et al. Mobilization of endothelial progenitor cells in fracture healing and distraction osteogenesis[J]. Bone, 2008;42(5):932-941.
[37]Gill M, Dias S, Hattori K, et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+)endothelial precursor cells[J]. Circulation Research,2001;88(2):167-174.
[38]Kalka C, Masuda H, Takahashi T, et al. Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects[J]. Circ Res,2000;86:1198-1202.
[39]Moore MA, Hattori K, Heissig B, et al.Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, andangiopoietin-1 [J]. Ann N Y Acad Sci, 2001;938:36-47.
[40]Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis[J]. Exp Cell Res, 2006;312(5):549-560.
[41]Strehlow K, Werner N, Berweiler J, et al. Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation[J]. Circulation,2003;107(24):3059-3065.
[42]Manalo DJ, Rowan A, Lavoie T, et al. Transcriptional regulation of vascular endothelial cell responses-to hypoxia by HIF-1[J]. Blood, 2005;105(2):659-669.
[43]Korbling M, Reuben JM, Gao H, et al. Recombinant human granulocyte-colony-stimulating factor-mobilized and apheresis-collected endothelial progenitor cells:a novel blood cell component for therapeutic vasculogenesis[J]. Transfusion,2006;46(10):1795-1802.
[44]Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells[J]. Hypertension,2005;45(3):321-325.
[45]陈君柱,张芙荣,朱建华,等.他汀类药物对外周血内皮祖细胞数量和功能的影响[J].中华心血管病杂志,2004；32：346-350.
[46]Pistrosch F, Herbrig K, Oelschlaegel U, et al. PPARgamma-agonist rosiglitazone increases number and migratory activity of cultured endothelial progenitor cells[J]. Atherosclerosis,2005;183(1):163-167.
[47]Hoetzer GL, Van Guilder GP, Irmiger HM, et al. Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men[J]. J Appl Physiol,2007; 102(3):847-852.
[48]Michaud SE, Dussault S, Haddad P, et al. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities[J]. Atherosclerosis,2006;187:423-432.
[49]Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells om the bone marrow niche requires MMP-9 mediated release of kit-ligand[J]. Cell,2002;109:625-637.
[50]Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells[J]. Nat Med,2003;9(11):1370-1376.
[51]Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy[J]. Lancet,2003;362:697-703.
[52]Lapidot T, Dar A, Kollet O. How do stem cells find their way home?[J]. Blood,2005;106:1901-1910.
[53]Hristov M, Erl W, Weber PC. Endothelial progenitor cells:mobilization, differentiation, and homing[J]. Arterioscler Thromb Vasc Biol, 2003;23(7):1185-1189.
[54]Borrello IM, Levitsky HI, Stock W, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)[J]. Blood, 2009;114(9):1736-1745.
[55]Frasci G, Comella P, Rinaldo M, et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer[J]. Ann Oncol,2009;20(7):1185-1192.
[56]Shergill AK, Khalili M, Straley S, et al. Applicability,tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation[J]. Am J Transplant,2005;5(1):118-124.
[57]Kim YJ, Shin JI, Park KW, et al. The effect of granulocyte-colony stimulating factor on endothelial function in patients with myocardial infarction[J]. Heart,2009;95(16):1320-1325.
[58]Eyles JL, Hickey MJ, Norman MU, et al. A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis [J]. Blood,2008;112(13):5193-51201.
[59]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;16:109-122.
[60]Shore PM, Jackson EK, Wisniewski SR, et al. Vascular endothelial growth factor is increased in cerebrospinal fluid after traumatic brain injury in infants and children[J]. Neurosurgery,2004;54(3):605-611.
[61]Skold MK, von Gertten C, Sandberg-Nordqvist AC, et al. VEGF and VEGF receptor expression after experimental brain contusion in rat[J]. J Neurotrauma,2005;22(3):353-367.
[62]Guo X, Liu L, Zhang M, et al. Correlation of CD34+ cells with Tissue Angiogenesis after Traumatic Brain Injury in a Rat Mode[J]. J Neurotrauma,2009;18:[Epub ahead of print].
[63]Rehman J, L i J, O rschell C, et al. Peripheral blood endothelial progenitor cells are derived from monocyte/macrophages and secrete angiogenic growth factors[J]. Circulation,2003; 107:1164-1169.
[64]Bingman VP, Sharp PE. Neuronal implementation of hippocampal-mediated spatial behavior:a comparative evolutionary perspective[J]. Behav Cogn Neurosci Rev,2006;5:80-91.
[65]Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke [J]. Nat Med, 2002;8:963-970.
[1]Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis[J]. Science,1997;275:964-967.
[2]Burgess A, Metcalf D. Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemia cells [J]. Int J Cancer, 1980;26(5):647-651.
[3]Borrello IM, Levitsky HI, Stock W, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)[J]. Blood,2009; 114(9):1736-1745.
[4]Frasci G, Comella P, Rinaldo M, et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer[J]. Ann Oncol,2009;20(7):1185-1192.
[5]Shergill AK, Khalili M, Straley S, et al. Applicability,tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation[J]. Am J Transplant,2005;5(1):118-124.
[6]Kim YJ, Shin JI, Park KW, et al. The effect of granulocyte-colony stimulating factor on endothelial function in patients with myocardial infarction[J]. Heart, 2009;95(16):1320-1325.
[7]Eyles JL, Hickey MJ, Norman MU, et al. A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis [J]. Blood, 2008;112(13):5193-51201.
[8]Bratane BT, Bouley J, Schneider A, et al. Granulocyte-colony stimulating factor delays PWI/DWI mismatch evolution and reduces final infarct volume in permanent-suture and embolic focal cerebral ischemia models in the rat[J]. Stroke,2009;40(9):3102-3106.
[9]Miranville A, Heeschen C, Sengenes C, et al. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells[J]. Circulation, 2004; 110:349-355.
[10]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;105:2783-2786.
[11]Tamaki T, Akatsuka A, Ando K, et al. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle[J]. J Cell Biol, 2002;157:571-577.
[12]Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand[J]. Cell, 2002;109:625-637.
[13]Mohle R, Bautz F, Rafii S, et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1[J]. Blood, 1998;91:4523-4530.
[14]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]. Exp Hematol,2002;30(8):967-972.
[15]Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-I alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovasculorization[J]. Circulation,2004;109(20):2454-2461.
[16]Mlhle R, Bsutz F, Rsfii S, et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor 1[J]. Blood, 1998:91(12):4523-4530.
[17]Badorff C, Brandes RP, Popp R, et al. Transdiferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes[J]. Circulation,2003;107(7):1024-1032.
[18]Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis[J]. Nat Med, 2002;8(4):403-409.
[19]Verama S, Kuliszewski MA, Li SH, et al. C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function[J]. Circulation, 2004;109(17):2058-2067.
[20]Szpak GM, Lechowicz W, Lewandowska E, et al. Border zone neovascularization in cerebral ischemic infarct[J]. Folia neuropathol, 1999;37(4):264-268.
[21]Taguchi A, Matsuyama T, Moriwaki H, et al. Circulating CD34-positive cells provide an index of cerebrovascular function[J]. Circulation, 2004; 109:2972-2975.
[22]Ghani U, Shuaib A, Salam A, et al. Endothelial progenitor cells during cerebrovascular disease[J]. Stroke,2005;36(1):151-153.
[23]Hon-Kan Yip, Li-Teh Chang, Wen-Neng Chang, et al. Level and Value of CirculatingEndothelial Progenitor Cells in Patients After Acute Ischemic Stroke[J]. Stroke,2008;39:69-74.
[24]Ohta T, Kikuta K, Imamura H, et al. Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats[J]. Neurosurgery,2006;59:679-686.
[25]Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis[J]. J Comp Neurol,2000;425:479-494.
[26]Leventhal C, Rafii S, Rafii D, et al. Endothelial trophic support of neuronal production and recruitment from the adult mammalian subependyma[J]. Mol Cell Neurosci,1999;13:450-464.
[27]Li L, Hui L, JF Jiao, et al. Changes in circulating human endothelial progenitor cells after brain injury [J]. J Neurotrauma,2007;24(6):936-943.
[28]John Glod, David Kobiler, Martha Noel, et al. Monocytes form a vascular barrier and participate in vessel repair after brain injury[J]. Blood,2006;107:940-946.
[29]Boneberg EM, Hartung T. Molecular aspects of anti-inflammatory action of G-CSF[J]. Inflamm Res,2002;51(3):119-128.
[30]Hoglund M. Glycosylated and non-glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF)-what is the difference? [J]. Med Oncol, 1998;15(4):229-233.
[31]Layton JE, Hall NE. The interaction of G-CSF with its receptor[J]. Front Biosci, 2006;1(11):3181-3189.
[32]Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis[J]. Clin Invest,2005;115:2083-2098.
[33]Park HK, Chu K, Lee ST, et al. Granulocyte colony-stimulating factor induces sensorimotor recovery in intracerebral hemorrhage [J]. Brain Res, 2005;1041:125-131.
[34]Gibson CL, Jones NC, Prior MJ, et al. G-CSF suppresses edema formation and reduces interleukin-1 expression after cerebral ischemia in mice[J]. J Neuropathol Exp Neurol,2005;64:763-769.
[35]Lee ST, Chu K, Jung KH, et al. Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia[J]. Brain Res,2005;1058:120-128.
[36]Barone FC, Feuerstein GZ. Inflammatory mediators and stroke:new opportunities for novel therapeutics [J]. J Cereb Blood Flow Metab, 1999; 19:819-834.
[37]Quagliarello VJ, Wispelwey B, Long WJ Jr, et al. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor [J]. J Clin Invest, 1991;87:1360-1366.
[38]Rosenman SJ, Shrikant P, Dubb L, et al. Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines[J]. J Immunol,1995;154:1888-1899.
[39]Zavala F, Abad S, Ezine S, et al. G-CSF therapy of ongoing experimental allergic encephalomyelitis via chemokine and cytokine-based immune deviation[J]. J Immunol,2002;168:2011-2019.
[40]Komine-Kobayashi M, Zhang N, Liu M, et al. Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice[J]. J Cereb Blood Flow Metab,2005; 27:[Epub ahead of print].
[41]Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia[J]. Stroke, 2003;34:745-751.
[42]Liu L, Cavanaugh JE, Wang Y, et al. ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons[J]. Proc Natl Acad Sci USA,2003;100:8532-8537.
[43]Wang L, Gang ZZ, Lan ZR, et al. Activation of the PI3-K/Akt pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricular zone[J]. J Cereb Blood Flow Metab,2005;25:1150-1158.
[44]Levesque JP, Hendy J, Takamatsu Y, et al. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide[J]. J Clin Invest,2003; 111:187-196.
[45]Grigg AP, Roberts AW, Raunow H, et al. Optimizing dose and scheduling of filgrastim (granulocyte colony-stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers[J]. Blood, 1995;86:4437-4445.
[46]Six I, Gasan G, Mura E, et al. Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia[J]. Eur J Pharmacol, 2003;458:327-328.
[47]Shyu WC, Lin SZ, Yang HI, et al. Functional recovery of stroke rats induced by granulocyte colony-stimulating factorstimulated stem cells[J]. Circulation, 2004;110:1847-1854.
[48]Ohki Y, Heissig B, Sato Y, et al. Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils[J]. FASEB J,2005;19(14):2005-2007.
[49]Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function[J]. Nat Med,2001;7(4):430-436.
[50]Shen Q, Goderie SK, Jin L,et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells[J]. Science,2004;304(5675):1338-1340.
[51]Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells[J]. Nat Med, 2003;9(11):1370-1376.
[2]杨树源,安沂华.再述神经干细胞的研究及应用前景[J].中华神经外科杂志,2002；18(5)：273-274.
[3]Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model [J]. J Clin Invest,2004;114:330-338.
[4]Shen Q, Goderie SK, Jin L, et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells [J]. Science, 2004;304(5675):1338-1340.
[5]Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis[J]. Science,1997;275:964-967.
[6]Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors [J]. Blood,2000;95:952-958.
[7]Hill JM, Zalos G. Circulating Endothelial progenitor cells, vascular function, and cardiovascular risk[J]. N Eng J Med,2003;348:593-600.
[8]Walter DH, Rittig K, Bahlmann FH, et al. Statin therapy accelerate reendothelialization:a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells[J]. Circulation,2002; 105:3017-3024.
[9]Murohara T, Ikeda H, Duan J, et al. Transplanted cord blood-derived endothelial progenitor cells augment postnatal neovascularization[J]. J Clin Invest,2000;105:1527-1536.
[10]Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function[J]. Nat Med,2001;7:430-436.
[11]Grant MB, May WS, Caballero S, et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization[J]. Nat Med,2002;8:607-612.
[12]Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cells significance in angiogenic growth factor-induced neovascularization[J]. Exp Hematol, 2002;30:967-972.
[13]Suzuki T, Nishida M, Futami S, et al. Neoendothelialization after peripheral blood stem cell transplantation in humans. A case report of a Tokaimura nuclear accident victim[J]. Cardiovasc Res,2003;58:487-492.
[14]Folkman J, Shing Y. Angiogenesis[J]. J Boil Chem, 1992;267(16):10931-10934.
[15]Risau W, Flamme I. Vasculogenesis[J]. Ann Rev Cell Dev Biol, 1995;11(9):79-91.
[16]Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells[J]. Blood,1998;92:362-367.
[17]Li Liu, Hui Liu,_JunFeng Jiao, et al._Changes in Circulating Human Endothelial Progenitor Cells after Brain Injury[J]. J Neurotrauma, 2007;24(6):936-943.
[18]John Glod, David Kobiler, Martha Noel,_et al. Monocytes form a vascular barrier and participate in vessel repair after brain injury[J].Blood, 2006;107:940-946.
[19]Morgan R, Kreipke CW, Roberts G,_et al._Neovascularization following traumatic brain injury:possible evidence for both angiogenesis and vasculogenesis[J]. Neurol Res,2007;29:375-381.
[20]Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration[J]. Nat Med,2003;9:702-712.
[21]Westenbrink BD, Lipsic E, van der Meer P, et al. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization[J]. Eur Heart J, 2007;28(16):2018-2027.
[22]Powell TM, Paul JD, Hill JM, et al. Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease[J]. Arterioscler Thromb Vasc Biol,2005;25(2):296-301.
[23]Takahashi T, Kalka C, Masuda H, et al. Ischemia and cytokine induced mobilization of bone marrow derived endothelial progenitor cells for neovascularization[J]. Nat Med,1999;5(4):434-438.
[24]Keswani SG, Katz AB, Lim FY, Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type Ⅰ and type Ⅱ diabetic wounds [J]. Wound Repair Regen,2004;12(5):497-504.
[25]Asahara T, Takahashi T, Masuda H, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow derived endothelial progenitor cells[J]. EMBO J,1999; 18(14):3964-3972.
[26]Heeschen C, Aicher A, Lehmann R, et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization[J]. Blood, 2003;102:1340-1346.
[27]Llevadot J, Murasawa S, Kureishi Y, et al. HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells[J]. J Clin Invest,2001;108:399-405.
[28]Iwakura A, Luedemann C, Shastry S, et al. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury[J]. Circulation,2003;108:3115-3121.
[29]Laufs U, Werner N, Link A, et al. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis[J]. Circulation,2004; 109:220-226.
[30]Ohki Y, Heissig B, Sato Y, et al. Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils[J]. FASEB J,2005;19(14):2005-2007.
[31]Honold J, Lehmann R, Heeschen C, et al. Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease[J]. Arterioscler Thromb Vasc Biol,2006;26(10):2238-2243.
[32]Gibson CL, Bath PM, Murphy SP. G-CSF reduces infarct volume and improves functional outcome after transient focal cerebral ischemia in mice[J]. J Cereb Blood Flow Metab,2005;25(4):431-439.
[33]McIntosh TK, Vink R, Noble L, et al. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model [J]. Neuroscience, 1989;28:233-244.
[34]Chen J, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats[J]. Stroke,2001;32(4):1005-1011.
[35]Massa M, Rosti V, Ferrario M, et al._Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction[J]. Blood,2005;105(1):199-206.
[36]Lee DY, Cho TJ, Kim JA, et al. Mobilization of endothelial progenitor cells in fracture healing and distraction osteogenesis[J]. Bone, 2008;42(5):932-941.
[37]Gill M, Dias S, Hattori K, et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+)endothelial precursor cells[J]. Circulation Research,2001;88(2):167-174.
[38]Kalka C, Masuda H, Takahashi T, et al. Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects[J]. Circ Res,2000;86:1198-1202.
[39]Moore MA, Hattori K, Heissig B, et al.Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, andangiopoietin-1 [J]. Ann N Y Acad Sci, 2001;938:36-47.
[40]Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis[J]. Exp Cell Res, 2006;312(5):549-560.
[41]Strehlow K, Werner N, Berweiler J, et al. Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation[J]. Circulation,2003;107(24):3059-3065.
[42]Manalo DJ, Rowan A, Lavoie T, et al. Transcriptional regulation of vascular endothelial cell responses-to hypoxia by HIF-1[J]. Blood, 2005;105(2):659-669.
[43]Korbling M, Reuben JM, Gao H, et al. Recombinant human granulocyte-colony-stimulating factor-mobilized and apheresis-collected endothelial progenitor cells:a novel blood cell component for therapeutic vasculogenesis[J]. Transfusion,2006;46(10):1795-1802.
[44]Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells[J]. Hypertension,2005;45(3):321-325.
[45]陈君柱,张芙荣,朱建华,等.他汀类药物对外周血内皮祖细胞数量和功能的影响[J].中华心血管病杂志,2004；32：346-350.
[46]Pistrosch F, Herbrig K, Oelschlaegel U, et al. PPARgamma-agonist rosiglitazone increases number and migratory activity of cultured endothelial progenitor cells[J]. Atherosclerosis,2005;183(1):163-167.
[47]Hoetzer GL, Van Guilder GP, Irmiger HM, et al. Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men[J]. J Appl Physiol,2007; 102(3):847-852.
[48]Michaud SE, Dussault S, Haddad P, et al. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities[J]. Atherosclerosis,2006;187:423-432.
[49]Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells om the bone marrow niche requires MMP-9 mediated release of kit-ligand[J]. Cell,2002;109:625-637.
[50]Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells[J]. Nat Med,2003;9(11):1370-1376.
[51]Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy[J]. Lancet,2003;362:697-703.
[52]Lapidot T, Dar A, Kollet O. How do stem cells find their way home?[J]. Blood,2005;106:1901-1910.
[53]Hristov M, Erl W, Weber PC. Endothelial progenitor cells:mobilization, differentiation, and homing[J]. Arterioscler Thromb Vasc Biol, 2003;23(7):1185-1189.
[54]Borrello IM, Levitsky HI, Stock W, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)[J]. Blood, 2009;114(9):1736-1745.
[55]Frasci G, Comella P, Rinaldo M, et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer[J]. Ann Oncol,2009;20(7):1185-1192.
[56]Shergill AK, Khalili M, Straley S, et al. Applicability,tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation[J]. Am J Transplant,2005;5(1):118-124.
[57]Kim YJ, Shin JI, Park KW, et al. The effect of granulocyte-colony stimulating factor on endothelial function in patients with myocardial infarction[J]. Heart,2009;95(16):1320-1325.
[58]Eyles JL, Hickey MJ, Norman MU, et al. A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis [J]. Blood,2008;112(13):5193-51201.
[59]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;16:109-122.
[60]Shore PM, Jackson EK, Wisniewski SR, et al. Vascular endothelial growth factor is increased in cerebrospinal fluid after traumatic brain injury in infants and children[J]. Neurosurgery,2004;54(3):605-611.
[61]Skold MK, von Gertten C, Sandberg-Nordqvist AC, et al. VEGF and VEGF receptor expression after experimental brain contusion in rat[J]. J Neurotrauma,2005;22(3):353-367.
[62]Guo X, Liu L, Zhang M, et al. Correlation of CD34+ cells with Tissue Angiogenesis after Traumatic Brain Injury in a Rat Mode[J]. J Neurotrauma,2009;18:[Epub ahead of print].
[63]Rehman J, L i J, O rschell C, et al. Peripheral blood endothelial progenitor cells are derived from monocyte/macrophages and secrete angiogenic growth factors[J]. Circulation,2003; 107:1164-1169.
[64]Bingman VP, Sharp PE. Neuronal implementation of hippocampal-mediated spatial behavior:a comparative evolutionary perspective[J]. Behav Cogn Neurosci Rev,2006;5:80-91.
[65]Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke [J]. Nat Med, 2002;8:963-970.
[1]Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis[J]. Science,1997;275:964-967.
[2]Burgess A, Metcalf D. Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemia cells [J]. Int J Cancer, 1980;26(5):647-651.
[3]Borrello IM, Levitsky HI, Stock W, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)[J]. Blood,2009; 114(9):1736-1745.
[4]Frasci G, Comella P, Rinaldo M, et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer[J]. Ann Oncol,2009;20(7):1185-1192.
[5]Shergill AK, Khalili M, Straley S, et al. Applicability,tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation[J]. Am J Transplant,2005;5(1):118-124.
[6]Kim YJ, Shin JI, Park KW, et al. The effect of granulocyte-colony stimulating factor on endothelial function in patients with myocardial infarction[J]. Heart, 2009;95(16):1320-1325.
[7]Eyles JL, Hickey MJ, Norman MU, et al. A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis [J]. Blood, 2008;112(13):5193-51201.
[8]Bratane BT, Bouley J, Schneider A, et al. Granulocyte-colony stimulating factor delays PWI/DWI mismatch evolution and reduces final infarct volume in permanent-suture and embolic focal cerebral ischemia models in the rat[J]. Stroke,2009;40(9):3102-3106.
[9]Miranville A, Heeschen C, Sengenes C, et al. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells[J]. Circulation, 2004; 110:349-355.
[10]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;105:2783-2786.
[11]Tamaki T, Akatsuka A, Ando K, et al. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle[J]. J Cell Biol, 2002;157:571-577.
[12]Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand[J]. Cell, 2002;109:625-637.
[13]Mohle R, Bautz F, Rafii S, et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1[J]. Blood, 1998;91:4523-4530.
[14]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]. Exp Hematol,2002;30(8):967-972.
[15]Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-I alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovasculorization[J]. Circulation,2004;109(20):2454-2461.
[16]Mlhle R, Bsutz F, Rsfii S, et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor 1[J]. Blood, 1998:91(12):4523-4530.
[17]Badorff C, Brandes RP, Popp R, et al. Transdiferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes[J]. Circulation,2003;107(7):1024-1032.
[18]Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis[J]. Nat Med, 2002;8(4):403-409.
[19]Verama S, Kuliszewski MA, Li SH, et al. C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function[J]. Circulation, 2004;109(17):2058-2067.
[20]Szpak GM, Lechowicz W, Lewandowska E, et al. Border zone neovascularization in cerebral ischemic infarct[J]. Folia neuropathol, 1999;37(4):264-268.
[21]Taguchi A, Matsuyama T, Moriwaki H, et al. Circulating CD34-positive cells provide an index of cerebrovascular function[J]. Circulation, 2004; 109:2972-2975.
[22]Ghani U, Shuaib A, Salam A, et al. Endothelial progenitor cells during cerebrovascular disease[J]. Stroke,2005;36(1):151-153.
[23]Hon-Kan Yip, Li-Teh Chang, Wen-Neng Chang, et al. Level and Value of CirculatingEndothelial Progenitor Cells in Patients After Acute Ischemic Stroke[J]. Stroke,2008;39:69-74.
[24]Ohta T, Kikuta K, Imamura H, et al. Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats[J]. Neurosurgery,2006;59:679-686.
[25]Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis[J]. J Comp Neurol,2000;425:479-494.
[26]Leventhal C, Rafii S, Rafii D, et al. Endothelial trophic support of neuronal production and recruitment from the adult mammalian subependyma[J]. Mol Cell Neurosci,1999;13:450-464.
[27]Li L, Hui L, JF Jiao, et al. Changes in circulating human endothelial progenitor cells after brain injury [J]. J Neurotrauma,2007;24(6):936-943.
[28]John Glod, David Kobiler, Martha Noel, et al. Monocytes form a vascular barrier and participate in vessel repair after brain injury[J]. Blood,2006;107:940-946.
[29]Boneberg EM, Hartung T. Molecular aspects of anti-inflammatory action of G-CSF[J]. Inflamm Res,2002;51(3):119-128.
[30]Hoglund M. Glycosylated and non-glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF)-what is the difference? [J]. Med Oncol, 1998;15(4):229-233.
[31]Layton JE, Hall NE. The interaction of G-CSF with its receptor[J]. Front Biosci, 2006;1(11):3181-3189.
[32]Schneider A, Kruger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis[J]. Clin Invest,2005;115:2083-2098.
[33]Park HK, Chu K, Lee ST, et al. Granulocyte colony-stimulating factor induces sensorimotor recovery in intracerebral hemorrhage [J]. Brain Res, 2005;1041:125-131.
[34]Gibson CL, Jones NC, Prior MJ, et al. G-CSF suppresses edema formation and reduces interleukin-1 expression after cerebral ischemia in mice[J]. J Neuropathol Exp Neurol,2005;64:763-769.
[35]Lee ST, Chu K, Jung KH, et al. Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia[J]. Brain Res,2005;1058:120-128.
[36]Barone FC, Feuerstein GZ. Inflammatory mediators and stroke:new opportunities for novel therapeutics [J]. J Cereb Blood Flow Metab, 1999; 19:819-834.
[37]Quagliarello VJ, Wispelwey B, Long WJ Jr, et al. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor [J]. J Clin Invest, 1991;87:1360-1366.
[38]Rosenman SJ, Shrikant P, Dubb L, et al. Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines[J]. J Immunol,1995;154:1888-1899.
[39]Zavala F, Abad S, Ezine S, et al. G-CSF therapy of ongoing experimental allergic encephalomyelitis via chemokine and cytokine-based immune deviation[J]. J Immunol,2002;168:2011-2019.
[40]Komine-Kobayashi M, Zhang N, Liu M, et al. Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice[J]. J Cereb Blood Flow Metab,2005; 27:[Epub ahead of print].
[41]Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia[J]. Stroke, 2003;34:745-751.
[42]Liu L, Cavanaugh JE, Wang Y, et al. ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons[J]. Proc Natl Acad Sci USA,2003;100:8532-8537.
[43]Wang L, Gang ZZ, Lan ZR, et al. Activation of the PI3-K/Akt pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricular zone[J]. J Cereb Blood Flow Metab,2005;25:1150-1158.
[44]Levesque JP, Hendy J, Takamatsu Y, et al. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide[J]. J Clin Invest,2003; 111:187-196.
[45]Grigg AP, Roberts AW, Raunow H, et al. Optimizing dose and scheduling of filgrastim (granulocyte colony-stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers[J]. Blood, 1995;86:4437-4445.
[46]Six I, Gasan G, Mura E, et al. Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia[J]. Eur J Pharmacol, 2003;458:327-328.
[47]Shyu WC, Lin SZ, Yang HI, et al. Functional recovery of stroke rats induced by granulocyte colony-stimulating factorstimulated stem cells[J]. Circulation, 2004;110:1847-1854.
[48]Ohki Y, Heissig B, Sato Y, et al. Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils[J]. FASEB J,2005;19(14):2005-2007.
[49]Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function[J]. Nat Med,2001;7(4):430-436.
[50]Shen Q, Goderie SK, Jin L,et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells[J]. Science,2004;304(5675):1338-1340.
[51]Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells[J]. Nat Med, 2003;9(11):1370-1376.
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