内皮祖细胞治疗脑创伤的研究进展
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摘要
内皮祖细胞(endothelial progenitor cells,EPCs)可促进创伤性脑损伤患者损伤区血管新生,并保护神经元的再生。近年来,外源性EPCs移植、动员内源性EPCs以及运用EPCs等治疗方法在创伤性脑损伤大鼠的实验研究中证实有很好的疗效,并表明EPCs的水平与脑创伤的恢复程度和预后密切相关。为了详细阐明最新相关研究,笔者就EPCs治疗创伤性脑损伤的作用机制、治疗策略、临床应用、预后作一综述。
Endothelial progenitor cells(EPC) can promote angiogenesis and neurogenesis in the traumatic brain injury. In recent years,the therapeutic strategies such as transplanting EPCs,mobilizing EPCs or the transplantation of endothelial progenitor cells exosomes,have proved to be effective and demonstrated that the level of EPCs is closely related to the degree of recovery and prognosis of brain traumatic in the experimental research. In order to illustrate the advances in the latest research,we make a review of the treatment mechanism of EPCs,therapeutic strategy,clinical application and the prognosis.
Endothelial progenitor cells(EPC) can promote angiogenesis and neurogenesis in the traumatic brain injury. In recent years,the therapeutic strategies such as transplanting EPCs,mobilizing EPCs or the transplantation of endothelial progenitor cells exosomes,have proved to be effective and demonstrated that the level of EPCs is closely related to the degree of recovery and prognosis of brain traumatic in the experimental research. In order to illustrate the advances in the latest research,we make a review of the treatment mechanism of EPCs,therapeutic strategy,clinical application and the prognosis.
引文
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[2] Yap YC,King AE,Guijt RM,et al.Mild and repetitive very mild axonal stretch injury triggers cystoskeletal mislocalization and growth cone collapse[J].PLoS One,2017,12(5):e0176997.
[3] Hawryluk GWJ,Bullock MR.Past,present,and future of traumatic brain injury research[J].Neurosur Clin North(Am),2016,27(4):375-396.
[4] Liu L,Wei H,Chen F,et al.Endothelial progenitor cells correlate with clinical outcome of traumatic brain injury[J].Crit Care Med,2011,39(7):1760-1765.
[5] Wagenfuhr L,Meyer AK,Marrone L,et al.Oxygen tension within the neurogenic niche regulates dopaminergic neurogenesis in the developing midbrain[J].Stem Cells Dev,2016,25(3):227-238.
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[7] Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endothelial cell for angiogenesis[J].Science,1997,275(5302):964-966.
[8] Hristov M,Weber C.Endothelial progenitor cells: characterization,pathophysiology and possible clinical relevance[J].J Cell Mol Med,2004,8(4):498-508.
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[11] Huang S,Tang Y,Cai X,et al.Celastrol inhibits vasculogenesis by suppressing the VEGF-induced functional activity of bone marrow-derived endothelial progenitor cells[J].Biochem Biophys Res Commun,2012,423(3):467-472.
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[15] Mochizuki M.Polo-like kinase 2 is dynamically regulated to coordinate proliferation and early lineage specification downstream of yes-associated protein 1 in cardiac progenitor cells[J].J Am Heart Assoc,2017,6(10):e005920
[16] Rosell A,Morancho A,Navarro-Sobrino M,et al.Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice[J].PLoS One,2013,8(9):e73244.
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[18] Xue S,Zhang HT,Zhang P,et al.Functional endothelial progenitor cells derived from adipose tissue show beneficial effect on cell therapy of traumatic brain injury [J].Neurosci Lett,2010,473(3):186-191.
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[20] Yu P,Li S,Zhang Z,et al.Progesterone-mediated angiogenic activity of endothelial progenitor cell and angiogenesis in traumatic brain injury rats were antagonized by progesterone receptor antagonist[J].Cell Prolif,2017,50(5): e12362.
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[22] Di Stefano R,Felice F,Feriani R,et al.Endothelial progenitor cells,cardiovascular risk factors and lifestyle modifications[J].Intern Emerg Med,2013,8 (S1):S47-49.
[23] Mao M,Xu X,Zhang Y,et al.Endothelial progenitor cells: the promise of cell-based therapies for acute lung injury[J].Inflamm Res,2013,62(1):3-8.
[24] Bitzer M,Ben-Dov IZ,Thum T,Microparticles and microRNAs of endothelial progenitor cells ameliorate acute kidney injury[J].Kidney Int,2012,82(4):375-377.
[25] 杨莹莹,陈秋娟,袁文,等.不同浓度雌激素对急性期高血压脑出血患者的内皮祖细胞功能及衰老的影响[J].山西医药杂志,2017,46(3):250-253.
[26] Wang L,Wang X,Tian Y,et al.Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in traumatic brain injury in rats[J].J Neurol Sci,2012,319(1-2):117-123.
[27] Chiang KH,Cheng WL,Shih CM,et al.Statins,HMG-CoA reductase inhibitors,improve neovascularization by increasing the expression density of CXCR4 in endothelial progenitor cells[J].PloS one,2015,10(8):e0136405
[28] Wang L,Wang X,Su H,et al.Recombinant human erythropoietin improves the neurofunctional recovery of rats following traumatic brain injury via an increase in circulating endothelial progenitor cells[J].Transl Stroke Res,2015,6(1):50-59.
[29] Yu P,Zhang Z,Li S,et al.Progesterone modulates endothelial progenitor cell (EPC) viability through the CXCL12/CXCR4/PI3K/Akt signaling pathway[J].Cell Prolif,2016,49(1):48-57.
[30] 李飞.内皮祖细胞来源外泌体对脑损伤小鼠血管修复作用的实验研究[D].天津医科大学,2017.
[31] Malaney P,Uversky VN,Dave V.PTEN proteoforms in biology and disease[J].Cell Mol Life Sci,2017,74(15):2783-2794.
[32] Xin H,Li Y,Buller B,et al.Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth[J].Stem Cells,2012,30(7):1556-1564.
[33] Fruhbeis C,Frohlich D,Kuo WP,et al.Extracellular vesicles as mediators of neuron-glia communication[J].Front Cell Neurosci,2013,7:182.
[34] Yang Z,Di Santo S,Kalka C.Current developments in the use of stem cell for therapeutic neovascularization: is the future therapy "cell-free"[J].Swiss Med Wkly,2010,140:w13130
[35] 王计伟,王毅,王东.不同程度颅脑创伤大鼠外周血内皮祖细胞动态变化及伤后认知能力的研究[J].天津医药,2018,46(2):139-143.
[36] Guo XB,Deng X,Wei Y.Homing of cultured endothelial progenitor cells and their effect their effect on traumatic brain injury in rat model[J].Sci Rep,2017,7(1):4164.
[37] 王文燕,张国华.干细胞移植治疗脑出血疗效研究进展[J].世界最新医学信息文摘,2018,18(2):115-116.
[38] Sun XQ,Ying JL,Wang YN, et al.Meta-analysis on autologous stem cell transplantation in the treatment of limb ischemic[J].Int J Clin Exp Med,2015,8(6): 8740-8748.
[2] Yap YC,King AE,Guijt RM,et al.Mild and repetitive very mild axonal stretch injury triggers cystoskeletal mislocalization and growth cone collapse[J].PLoS One,2017,12(5):e0176997.
[3] Hawryluk GWJ,Bullock MR.Past,present,and future of traumatic brain injury research[J].Neurosur Clin North(Am),2016,27(4):375-396.
[4] Liu L,Wei H,Chen F,et al.Endothelial progenitor cells correlate with clinical outcome of traumatic brain injury[J].Crit Care Med,2011,39(7):1760-1765.
[5] Wagenfuhr L,Meyer AK,Marrone L,et al.Oxygen tension within the neurogenic niche regulates dopaminergic neurogenesis in the developing midbrain[J].Stem Cells Dev,2016,25(3):227-238.
[6] Pearn ML,Niesman IR,Egawa J,et al.Pathophysiology associated with traumatic brain injury.Current treatments and potential novel therapeutics [J].Cell Mol Neurobiol,2017,37(4):571-585.
[7] Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endothelial cell for angiogenesis[J].Science,1997,275(5302):964-966.
[8] Hristov M,Weber C.Endothelial progenitor cells: characterization,pathophysiology and possible clinical relevance[J].J Cell Mol Med,2004,8(4):498-508.
[9] 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.
[10] Urbich C,Aicher A,Heeschen C,et al.Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells[J].J Mol Cell Cardiol,2005,39(5):733-742.
[11] Huang S,Tang Y,Cai X,et al.Celastrol inhibits vasculogenesis by suppressing the VEGF-induced functional activity of bone marrow-derived endothelial progenitor cells[J].Biochem Biophys Res Commun,2012,423(3):467-472.
[12] Lampugnani MG,Resnati M,Raiteri M,et al.A novel endothelial-specific membrane protein is a marker of cell-cell contacts[J].J Cell Biol,1992,118(6):1511-1522。
[13] Murota SI,Onodera M,Morita I.Regulation of angiogenesis by controlling VEGF receptor[J].Ann N Y Acad Sci,2000,902:208-212.
[14] Nejigane S.Hippo signaling components,Mst1 and Mst2,act as a switch between self-renewal and differentiation in Xenopus hematopoietic and endothelial progenitors[J].Int J Dev Biol,2013,57(5): 407-414.
[15] Mochizuki M.Polo-like kinase 2 is dynamically regulated to coordinate proliferation and early lineage specification downstream of yes-associated protein 1 in cardiac progenitor cells[J].J Am Heart Assoc,2017,6(10):e005920
[16] Rosell A,Morancho A,Navarro-Sobrino M,et al.Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice[J].PLoS One,2013,8(9):e73244.
[17] Park KJ,Park E,Liu E,et al.Bone marrow-derived endothelial progenitor cells protect postischemic axons after traumatic brain injury[J].J Cereb Blood Flow Metab,2014,34(2):357-366.
[18] Xue S,Zhang HT,Zhang P,et al.Functional endothelial progenitor cells derived from adipose tissue show beneficial effect on cell therapy of traumatic brain injury [J].Neurosci Lett,2010,473(3):186-191.
[19] Park E,Park K,Liu E,et al.Bone-marrow-derived endothelial progenitor cell treatment in a model of lateral fluid percussion injury in rats: evaluation of acute and subacute outcome measures[J].J Neurotrauma,2017,34(19):2801-2811.
[20] Yu P,Li S,Zhang Z,et al.Progesterone-mediated angiogenic activity of endothelial progenitor cell and angiogenesis in traumatic brain injury rats were antagonized by progesterone receptor antagonist[J].Cell Prolif,2017,50(5): e12362.
[21] 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.
[22] Di Stefano R,Felice F,Feriani R,et al.Endothelial progenitor cells,cardiovascular risk factors and lifestyle modifications[J].Intern Emerg Med,2013,8 (S1):S47-49.
[23] Mao M,Xu X,Zhang Y,et al.Endothelial progenitor cells: the promise of cell-based therapies for acute lung injury[J].Inflamm Res,2013,62(1):3-8.
[24] Bitzer M,Ben-Dov IZ,Thum T,Microparticles and microRNAs of endothelial progenitor cells ameliorate acute kidney injury[J].Kidney Int,2012,82(4):375-377.
[25] 杨莹莹,陈秋娟,袁文,等.不同浓度雌激素对急性期高血压脑出血患者的内皮祖细胞功能及衰老的影响[J].山西医药杂志,2017,46(3):250-253.
[26] Wang L,Wang X,Tian Y,et al.Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in traumatic brain injury in rats[J].J Neurol Sci,2012,319(1-2):117-123.
[27] Chiang KH,Cheng WL,Shih CM,et al.Statins,HMG-CoA reductase inhibitors,improve neovascularization by increasing the expression density of CXCR4 in endothelial progenitor cells[J].PloS one,2015,10(8):e0136405
[28] Wang L,Wang X,Su H,et al.Recombinant human erythropoietin improves the neurofunctional recovery of rats following traumatic brain injury via an increase in circulating endothelial progenitor cells[J].Transl Stroke Res,2015,6(1):50-59.
[29] Yu P,Zhang Z,Li S,et al.Progesterone modulates endothelial progenitor cell (EPC) viability through the CXCL12/CXCR4/PI3K/Akt signaling pathway[J].Cell Prolif,2016,49(1):48-57.
[30] 李飞.内皮祖细胞来源外泌体对脑损伤小鼠血管修复作用的实验研究[D].天津医科大学,2017.
[31] Malaney P,Uversky VN,Dave V.PTEN proteoforms in biology and disease[J].Cell Mol Life Sci,2017,74(15):2783-2794.
[32] Xin H,Li Y,Buller B,et al.Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth[J].Stem Cells,2012,30(7):1556-1564.
[33] Fruhbeis C,Frohlich D,Kuo WP,et al.Extracellular vesicles as mediators of neuron-glia communication[J].Front Cell Neurosci,2013,7:182.
[34] Yang Z,Di Santo S,Kalka C.Current developments in the use of stem cell for therapeutic neovascularization: is the future therapy "cell-free"[J].Swiss Med Wkly,2010,140:w13130
[35] 王计伟,王毅,王东.不同程度颅脑创伤大鼠外周血内皮祖细胞动态变化及伤后认知能力的研究[J].天津医药,2018,46(2):139-143.
[36] Guo XB,Deng X,Wei Y.Homing of cultured endothelial progenitor cells and their effect their effect on traumatic brain injury in rat model[J].Sci Rep,2017,7(1):4164.
[37] 王文燕,张国华.干细胞移植治疗脑出血疗效研究进展[J].世界最新医学信息文摘,2018,18(2):115-116.
[38] Sun XQ,Ying JL,Wang YN, et al.Meta-analysis on autologous stem cell transplantation in the treatment of limb ischemic[J].Int J Clin Exp Med,2015,8(6): 8740-8748.