间充质干细胞治疗心肌梗死的研究进展
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摘要
间充质干细胞广泛存在于骨髓、外周血、脐带、胎盘、脂肪及牙髓等组织。由于其具有高度自我增殖能力与多向分化潜能,可分化为心肌样细胞和内皮细胞。促进血管新成,并通过旁分泌途径改善心功能,为心肌梗死的治疗研究提供新选择,现就其在心肌梗死治疗中的现状及进展做全面概述。
Mesenchymal stem cells(MSCs) are a category of stem cells that are isolated from a variety of tissues, including bone marrow, peripheral blood, umbilical cord, placenta, adipose tissue, dental pulp, etc. On account of their capacity of selfproliferation and multilineage differentiation, MSCs can differentiate into cardiomyocytes and endothelial cells, which contributes to the angiogenesis. Furthermore, MSCs are beneficial to improve the cardiac function via the paracrine mechanism and bring the new option to the treatments of myocardial infarction. This current review provides overviews of the present situation and advances made in the treatments of myocardial infarction using mesenchymal stem cells.
Mesenchymal stem cells(MSCs) are a category of stem cells that are isolated from a variety of tissues, including bone marrow, peripheral blood, umbilical cord, placenta, adipose tissue, dental pulp, etc. On account of their capacity of selfproliferation and multilineage differentiation, MSCs can differentiate into cardiomyocytes and endothelial cells, which contributes to the angiogenesis. Furthermore, MSCs are beneficial to improve the cardiac function via the paracrine mechanism and bring the new option to the treatments of myocardial infarction. This current review provides overviews of the present situation and advances made in the treatments of myocardial infarction using mesenchymal stem cells.
引文
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[3]FAZZI R,PACINI S,CARNICELLI V,et al.Mesodermal progenitor cells(MPCs)differentiate into mesenchymal stromal cells(MSCs)by activation of Wnt5/calmodulin signalling pathway[J].PLoS One,2011,6(9):e25600.
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[6]CAPLAN AI.Mesenchymal stem cells[J].J Orthop Res,1991,9(5):641-650.
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[8]DE MIGUEL MP,FUENTES-JULIAN S,BLAZQUEZ-MARTINEZA,et al.Immunosuppressive properties of mesenchymal stem cells:advances and applications[J].Curr Mol Med,2012,12(5):574-591.
[9]ABUMAREE MH,AL JM,KALIONIS B,et al.Human placental mesenchymal stem cells(pMSCs)play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1to anti-inflammatory M2 macrophages[J].Stem Cell Rev,2013,9(5):620-641.
[10]SAITO T,KUANG JQ,BITTIRA B,et al.Xenotransplant cardiac chimera:immune tolerance of adult stem cells[J].Ann Thorac Surg,2002,74(1):19-24,24.
[11]BARBASH IM,CHOURAQUI P,BARON J,et al.Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium:feasibility,cell migration,and body distribution[J].Circulation,2003,108(7):863-868.
[12]CHENG M,HUANG K,ZHOU J,et al.A critical role of Src family kinase in SDF-1/CXCR4-mediated bone-marrow progenitor cell recruitment to the ischemic heart[J].J Mol Cell Cardiol,2015,81:49-53.
[13]KHAN I,ALI A,AKHTER MA,et al.Epac-Rap1-activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction[J].Cardiovasc Ther,2017,35(2),e12248.
[14]TOMITA S,LI RK,WEISEL RD,et al.Autologous transplantation of bone marrow cells improves damaged heart function[J].Circulation,1999,100(19 Suppl):II247-II256.
[15]KANG PL,CHEN CH,CHEN SY,et al.Nano-sized collagen Imolecules enhanced the differentiation of rat mesenchymal stem cells into cardiomyocytes[J].J Biomed Mater Res A,2013,101(10):2808-2816.
[16]BOBI J,SOLANES N,FERNáNDEZ-JIMéNEZ R,et al.Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function,in a translational model of acute myocardial infarction[J].J Am Heart Assoc,2017,6(5):e005771.
[17]ZHANG Z,YANG J,YAN W,et al.Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair[J].J Am Heart Assoc,2016,5(1):e002856.
[18]MAO Q,LIN C,GAO J,et al.Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction[J].Mol Cell Biochem,2014,397(1-2):203-214.
[19]JIANG W,MA A,WANG T,et al.Homing and differentiation of mesenchymal stem cells delivered intravenously to ischemic myocardium in vivo:a time-series study[J].Pflügers Archiv,2006,453(1):43-52.
[20]CHEN XQ,CHEN LL,FAN L,et al.Stem cells with FGF4-bFGF fused gene enhances the expression of bFGF and improves myocardial repair in rats[J].Biochem Biophys Res Commun,2014,447(1):145-151.
[21]KRAMPERA M,COSMI L,ANGELI R,et al.Role for interferongamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells[J].Stem Cells,2006,24(2):386-398.
[22]LUGER D,LIPINSKI MJ,WESTMAN PC,et al.Intravenously delivered mesenchymal stem cells:systemic anti-inflammatory effects improve left ventricular dysfunction in acute myocardial infarction and ischemic cardiomyopathy[J].Circ Res,2017,120(10):1598-1613.
[23]ASSIS AC,CARVALHO JL,JACOBY BA,et al.Time-dependent migration of systemically delivered bone marrow mesenchymal stem cells to the infarcted heart[J].Cell Transplant,2010,19(2):219-230.
[24]LI L,WU S,LIU Z,et al.Ultrasound-targeted microbubble destruction improves the migration and homing of mesenchymal stem gells after myocardial infarction by upregulating SDF-1/CXCR4:a pilot study[J].Stem Cells International,2015,2015:1-14.
[25]LUO L,TANG J,NISHI K,et al.Fabrication of synthetic mesenchymal stem cells for the treatment of acute myocardial infarction in mice[J].Circ Res,2017,120(11):1768-1775.
[26]KHAN I,ALI A,AKHTER MA,et al.Preconditioning of mesenchymal stem cells with 2,4-dinitrophenol improves cardiac function in infarcted rats[J].Life Sci,2016,162:60-69.
[27]HE H,ZHAO ZH,HAN FS,et al.Overexpression of protein kinase C?improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction[J].Cell Death Dis,2016,7(1):e2056.
[28]SONG L,YANG YJ,DONG QT,et al.Atorvastatin enhance efficacy of mesenchymal stem cells treatment for swine myocardial infarction via activation of nitric oxide synthase[J].PLoS One,2013,8(5):e65702.
[29]YAN W,GUO Y,TAO L,et al.C1q/tumor necrosis factor-related protein-9 regulates the fate of implanted mesenchymal stem cells and mobilizes their protective effects against ischemic heart injury via multiple novel signaling pathways[J].Circulation,2017,136(22):2162-2177.
[30]CHEN SL,FANG WW,QIAN J,et al.Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction[J].Chin Med J(Engl),2004,117(10):1443-1448.
[31]LEISTNER DM,FISCHER-RASOKAT U,HONOLD J,et al.Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction(TOPCARE-AMI):final 5-year results suggest long-term safety and efficacy[J].Clinical Research in Cardiology,2011,100(10):925-934.
[32]CHULLIKANA A,MAJUMDAR AS,GOTTIPAMULA S,et al.Randomized,double-blind,phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction[J].Cytotherapy,2015,17(3):250-261.
[33]LALU MM,MAZZARELLO S,ZLEPNIG J,et al.Safety and efficacy of adult stem cell therapy for acute myocardial infarction and ischemic heart failure(safecell heart):a systematic review and meta-analysis[J].Stem Cells Transl Med,2018,7(12):857-866.
[2]MAKINO S,FUKUDA K,MIYOSHI S,et al.Cardiomyocytes can be generated from marrow stromal cells in vitro[J].The Journal of Clinical Investigation,1999,103(5):697-705.
[3]FAZZI R,PACINI S,CARNICELLI V,et al.Mesodermal progenitor cells(MPCs)differentiate into mesenchymal stromal cells(MSCs)by activation of Wnt5/calmodulin signalling pathway[J].PLoS One,2011,6(9):e25600.
[4]ZHAO RC.Essentials of mesenchymal stem cell biology and its clinical translation[M].Springer Netherlands,2013:17-32.
[5]FRIEDENSTEIN AJ,CHAILAKHYAN RK,GERASIMOVUV.Bone marrow osteogenic stem cells:in vitro cultivation and transplantation in diffusion chambers[J].Cell Tissue Kinet,1987,20(3):263-272.
[6]CAPLAN AI.Mesenchymal stem cells[J].J Orthop Res,1991,9(5):641-650.
[7]DOMINICI M,LE BLANC K,MUELLER I,et al.Minimal criteria for defining multipotent mesenchymal stromal cells.The International Society for Cellular Therapy position statement[J].Cytotherapy,2006,8(4):315-317.
[8]DE MIGUEL MP,FUENTES-JULIAN S,BLAZQUEZ-MARTINEZA,et al.Immunosuppressive properties of mesenchymal stem cells:advances and applications[J].Curr Mol Med,2012,12(5):574-591.
[9]ABUMAREE MH,AL JM,KALIONIS B,et al.Human placental mesenchymal stem cells(pMSCs)play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1to anti-inflammatory M2 macrophages[J].Stem Cell Rev,2013,9(5):620-641.
[10]SAITO T,KUANG JQ,BITTIRA B,et al.Xenotransplant cardiac chimera:immune tolerance of adult stem cells[J].Ann Thorac Surg,2002,74(1):19-24,24.
[11]BARBASH IM,CHOURAQUI P,BARON J,et al.Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium:feasibility,cell migration,and body distribution[J].Circulation,2003,108(7):863-868.
[12]CHENG M,HUANG K,ZHOU J,et al.A critical role of Src family kinase in SDF-1/CXCR4-mediated bone-marrow progenitor cell recruitment to the ischemic heart[J].J Mol Cell Cardiol,2015,81:49-53.
[13]KHAN I,ALI A,AKHTER MA,et al.Epac-Rap1-activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction[J].Cardiovasc Ther,2017,35(2),e12248.
[14]TOMITA S,LI RK,WEISEL RD,et al.Autologous transplantation of bone marrow cells improves damaged heart function[J].Circulation,1999,100(19 Suppl):II247-II256.
[15]KANG PL,CHEN CH,CHEN SY,et al.Nano-sized collagen Imolecules enhanced the differentiation of rat mesenchymal stem cells into cardiomyocytes[J].J Biomed Mater Res A,2013,101(10):2808-2816.
[16]BOBI J,SOLANES N,FERNáNDEZ-JIMéNEZ R,et al.Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function,in a translational model of acute myocardial infarction[J].J Am Heart Assoc,2017,6(5):e005771.
[17]ZHANG Z,YANG J,YAN W,et al.Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair[J].J Am Heart Assoc,2016,5(1):e002856.
[18]MAO Q,LIN C,GAO J,et al.Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction[J].Mol Cell Biochem,2014,397(1-2):203-214.
[19]JIANG W,MA A,WANG T,et al.Homing and differentiation of mesenchymal stem cells delivered intravenously to ischemic myocardium in vivo:a time-series study[J].Pflügers Archiv,2006,453(1):43-52.
[20]CHEN XQ,CHEN LL,FAN L,et al.Stem cells with FGF4-bFGF fused gene enhances the expression of bFGF and improves myocardial repair in rats[J].Biochem Biophys Res Commun,2014,447(1):145-151.
[21]KRAMPERA M,COSMI L,ANGELI R,et al.Role for interferongamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells[J].Stem Cells,2006,24(2):386-398.
[22]LUGER D,LIPINSKI MJ,WESTMAN PC,et al.Intravenously delivered mesenchymal stem cells:systemic anti-inflammatory effects improve left ventricular dysfunction in acute myocardial infarction and ischemic cardiomyopathy[J].Circ Res,2017,120(10):1598-1613.
[23]ASSIS AC,CARVALHO JL,JACOBY BA,et al.Time-dependent migration of systemically delivered bone marrow mesenchymal stem cells to the infarcted heart[J].Cell Transplant,2010,19(2):219-230.
[24]LI L,WU S,LIU Z,et al.Ultrasound-targeted microbubble destruction improves the migration and homing of mesenchymal stem gells after myocardial infarction by upregulating SDF-1/CXCR4:a pilot study[J].Stem Cells International,2015,2015:1-14.
[25]LUO L,TANG J,NISHI K,et al.Fabrication of synthetic mesenchymal stem cells for the treatment of acute myocardial infarction in mice[J].Circ Res,2017,120(11):1768-1775.
[26]KHAN I,ALI A,AKHTER MA,et al.Preconditioning of mesenchymal stem cells with 2,4-dinitrophenol improves cardiac function in infarcted rats[J].Life Sci,2016,162:60-69.
[27]HE H,ZHAO ZH,HAN FS,et al.Overexpression of protein kinase C?improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction[J].Cell Death Dis,2016,7(1):e2056.
[28]SONG L,YANG YJ,DONG QT,et al.Atorvastatin enhance efficacy of mesenchymal stem cells treatment for swine myocardial infarction via activation of nitric oxide synthase[J].PLoS One,2013,8(5):e65702.
[29]YAN W,GUO Y,TAO L,et al.C1q/tumor necrosis factor-related protein-9 regulates the fate of implanted mesenchymal stem cells and mobilizes their protective effects against ischemic heart injury via multiple novel signaling pathways[J].Circulation,2017,136(22):2162-2177.
[30]CHEN SL,FANG WW,QIAN J,et al.Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction[J].Chin Med J(Engl),2004,117(10):1443-1448.
[31]LEISTNER DM,FISCHER-RASOKAT U,HONOLD J,et al.Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction(TOPCARE-AMI):final 5-year results suggest long-term safety and efficacy[J].Clinical Research in Cardiology,2011,100(10):925-934.
[32]CHULLIKANA A,MAJUMDAR AS,GOTTIPAMULA S,et al.Randomized,double-blind,phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction[J].Cytotherapy,2015,17(3):250-261.
[33]LALU MM,MAZZARELLO S,ZLEPNIG J,et al.Safety and efficacy of adult stem cell therapy for acute myocardial infarction and ischemic heart failure(safecell heart):a systematic review and meta-analysis[J].Stem Cells Transl Med,2018,7(12):857-866.