间充质干细胞在脑卒中治疗中的研究现状分析
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摘要
脑卒中是临床上难以攻克的一类神经系统疾病。以间充质干细胞(MSC)为基础的细胞移植为广大脑卒中患者健康的恢复带来了希望,但目前对MSC用于脑卒中治疗的研究不够透彻,仍然面临一些问题。该文旨在从MSC的组织来源、制备流程、时间窗、移植途径、预处理、联合用药、示踪方法等角度,对其在脑卒中治疗中面临的一些问题进行综述,以期为科研和临床应用提供指导。
Stroke is a neurological disease which is difficult to conquer clinically. Cell transplantation based on mesenchymal stem cells( MSCs) provides hope for the healthy recovery of stroke patients,but our study of MSCs for stroke therapy is not thorough enough and still faces some problems. The aim of this paper is to summarize the problems with MSCs in the treatment of stroke from the perspectives of tissue source,preparation process,time window,transplantation pathway,pretreatment,combined medication and tracer method,in order to provide guidance for scientific research and clinical application.
Stroke is a neurological disease which is difficult to conquer clinically. Cell transplantation based on mesenchymal stem cells( MSCs) provides hope for the healthy recovery of stroke patients,but our study of MSCs for stroke therapy is not thorough enough and still faces some problems. The aim of this paper is to summarize the problems with MSCs in the treatment of stroke from the perspectives of tissue source,preparation process,time window,transplantation pathway,pretreatment,combined medication and tracer method,in order to provide guidance for scientific research and clinical application.
引文
[1]陶然,韩焱福,柴家科.人脐带组织间充质干细胞研究进展及应用前景[J].军事医学科学院院刊,2010,34(3):293-296.
[2]Bajek A,Gurtowska N,Olkowska J,et al.Adipose-derived stem cells as a tool in cell-based therapies[J].Arch Immunol Ther Exp,2016,64(6):443-454.
[3]李艳琪,王洪一,姚尧,等.人脐带源和胎盘源间充质干细胞的生物学特性比较[J].军事医学,2015,39(6):418-422.
[4]邓力,黄永灿.胎盘组织——间充质干细胞的新来源[J].中国医药生物技术,2009,(4):285-287.
[5]李晓峰,赵劲民,苏伟,等.大鼠骨髓间充质干细胞的培养与鉴定[J].中国组织工程研究与临床康复,2011,15(10):1721-1725.
[6]刘晓丹,郭子宽,李秀森,等.人骨髓间充质干细胞分离与培养方法的建立[J].军事医学科学院院刊,2000,24(4):282-284.
[7]范宏杰,刘利龙,黄建强,等.间充质干细胞的临床应用若干问题[J].东南国防医药,2017,19(3):285-289.
[8]郭子宽.间充质干细胞及其临床应用中的几个问题[J].中国组织工程研究,2012,16(1):1-10.
[9]孙瑞婷,陈瑶瑶,王华,等.脐带来源间充质干细胞的制备及其质量检定[J].中国医药生物技术,2013,8(6):401-407.
[10]MakelaT,Takalo R,Arvola O,et al.Safety and biodistribution study of bone marrow-derived mesenchymal stromal cells and mononuclear cells and the impact of the administration route in an intact porcine model[J].Cytotherapy,2015,17(4):392-402.
[11]Yavagal DR,Lin B,Raval AP,et al.Efficacy and dose-dependent safety of intra-arterial delivery of mesenchymal stem cells in a rodent stroke model[J].PLo S One,2014,9(5):e93735.
[12]Janowski M,Lyczek A,Engels C,et al.Cell size and velocity of injection are major determinants of the safety of intracarotid stem cell transplantation[J].J Cereb Blood Flow Metab,2013,33(6):921-927.
[13]Cui LL,KerkelaE,Bakreen A,et al.The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity[J].Stem Cell Res Ther,2015,6:11.
[14]Rosenblum S,Wang N,Smith TN,et al.Timing of intra-arterial neural stem cell transplantation after hypoxia-ischemia influences cell engraftment,survival,and differentiation[J].Stroke,2012,43(6):1624-1631.
[15]Wei N,Yu SP,Gu X,et al.Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice[J].Cell Transplant,2013,22(6):977-991.
[16]Tsai LK,Wang Z,Munasinghe J,et al.Mesenchymal stem cells primed with valproate and lithium robustly migrate to infarcted regions and facilitate recovery in a stroke model[J].Stroke,2011,42(10):2932-2939.
[17]Ikeda N,Nonoguchi N,Zhao MZ,et al.Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats[J].Stroke,2005,36(12):2725-2730.
[18]边莉,郭子宽,艾辉胜,等.HGF基因修饰增强间充质干细胞的免疫抑制作用[J].军事医学科学院院刊,2006,30(4):323-328.
[19]Zhao Y,Lai W,Xu Y,et al.Exogenous and endogenous therapeutic effects of combination sodium ferulate and bone marrow stromal cells(BMSCs)treatment enhance neurogenesis after rat focal cerebral ischemia[J].Metab Brain Dis,2013,28(4):655-666.
[20]Lee YS,Chio CC,Chang CP,et al.Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke[J].Mediators Inflamm,2013,2013:512978.
[21]Guan Y,Zhao YH.Treatment of cerebral ischemia with combination of bone marrow-derived mesenchymal stem cells and Chinese medicine[J].Chin J Integr Med,2011,17(9):715-720.
[22]Zhang GW,Gu TX,Sun XJ,et al.Edaravone promotes activation of resident cardiac stem cells by transplanted mesenchymal stem cells in a rat myocardial infarction model[J].J Thorac Cardiovasc Surg,2016,152(2):570-582.
[23]Tari K,Atashi A,Kaviani S,et al.Erythropoietin induces production of hepatocyte growth factor from bone marrow mesenchymal stem cells in vitro[J].Biologicals,2017,45:15-19.
[24]Lu H,Wu X,Wang Z,et al.Erythropoietin-activated mesenchymal stem cells promote healing ulcers by improving microenvironment[J].J Surg Res,2016,205(2):464-473.
[25]Fuseler JW,Valarmathi MT.Nitric oxide modulates postnatal bone marrow-derived mesenchymal stem cell migration[J].Front Cell Dev Biol,2016,4:133.
[26]Bulte JW.In vivo MRI cell tracking:clinical studies[J].Am J Roentgenol,2009,193(2):314-325.
[27]Wolfs E,Verfaillie CM,Van Laere K,et al.Radiolabeling strategies for radionuclide imaging of stem cells[J].Stem Cell Rev,2015,11(2):254-274.
[28]Vandsburger MH,Radoul M,Cohen B,et al.MRI Reporter genes:applications for imaging of cell survival,proliferation,migration and differentiation[J].NMR Biomed,2013,26(7):872-884.
[29]Gu E,Chen WY,Gu J,et al.Molecular imaging of stem cells:tracking survival,biodistribution,tumorigenicity,and immunogenicity[J].Theranostics,2012,2(4):335-345.
[30]Tang Y,Zhang C,Wang J,et al.MRI/SPECT/Fluorescent trimodal probe for evaluating the homing and therapeutic efficacy of transplanted mesenchymal stem cells in a rat ischemic stroke model[J].Adv Funct Mater,2015,25(7):1024-1034.
[31]Scheller A,Vivien D,Kirchhoff F,et al.Imaging neuroinflammation after brain injuries by ultrasensitive MRI and two-photon laser-scanning microscopy[J].Rom J Morphol Embryol,2014,55(3):735-743.
[32]Zhang X,Li CX.Arterial spin labeling perfusion magnetic resonance imaging of non-human primates[J].Quant Imaging Med Surg,2016,6(5):573-581.
[33]Raval AP,Saul I,Dave KR,et al.Pretreatment with a single estradiol-17βbolus activates cyclic-AMP response element binding protein and protects CA1 neurons against global cerebral ischemia[J].Neuroscience,2009,160(2):307-318.
[34]Amariglio N,Hirshberg A,Scheithauer BW,et al.Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient[J].PLo S Med,2009,6(2):e1000029.
[35]Tang G,Liu Y,Zhang Z,et al.Mesenchymal stem cells maintain blood-brain barrier integrity by inhibiting aquaporin-4 upregulation after cerebral ischemia[J].Stem Cells,2014,32(12):3150-3162.
[2]Bajek A,Gurtowska N,Olkowska J,et al.Adipose-derived stem cells as a tool in cell-based therapies[J].Arch Immunol Ther Exp,2016,64(6):443-454.
[3]李艳琪,王洪一,姚尧,等.人脐带源和胎盘源间充质干细胞的生物学特性比较[J].军事医学,2015,39(6):418-422.
[4]邓力,黄永灿.胎盘组织——间充质干细胞的新来源[J].中国医药生物技术,2009,(4):285-287.
[5]李晓峰,赵劲民,苏伟,等.大鼠骨髓间充质干细胞的培养与鉴定[J].中国组织工程研究与临床康复,2011,15(10):1721-1725.
[6]刘晓丹,郭子宽,李秀森,等.人骨髓间充质干细胞分离与培养方法的建立[J].军事医学科学院院刊,2000,24(4):282-284.
[7]范宏杰,刘利龙,黄建强,等.间充质干细胞的临床应用若干问题[J].东南国防医药,2017,19(3):285-289.
[8]郭子宽.间充质干细胞及其临床应用中的几个问题[J].中国组织工程研究,2012,16(1):1-10.
[9]孙瑞婷,陈瑶瑶,王华,等.脐带来源间充质干细胞的制备及其质量检定[J].中国医药生物技术,2013,8(6):401-407.
[10]MakelaT,Takalo R,Arvola O,et al.Safety and biodistribution study of bone marrow-derived mesenchymal stromal cells and mononuclear cells and the impact of the administration route in an intact porcine model[J].Cytotherapy,2015,17(4):392-402.
[11]Yavagal DR,Lin B,Raval AP,et al.Efficacy and dose-dependent safety of intra-arterial delivery of mesenchymal stem cells in a rodent stroke model[J].PLo S One,2014,9(5):e93735.
[12]Janowski M,Lyczek A,Engels C,et al.Cell size and velocity of injection are major determinants of the safety of intracarotid stem cell transplantation[J].J Cereb Blood Flow Metab,2013,33(6):921-927.
[13]Cui LL,KerkelaE,Bakreen A,et al.The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity[J].Stem Cell Res Ther,2015,6:11.
[14]Rosenblum S,Wang N,Smith TN,et al.Timing of intra-arterial neural stem cell transplantation after hypoxia-ischemia influences cell engraftment,survival,and differentiation[J].Stroke,2012,43(6):1624-1631.
[15]Wei N,Yu SP,Gu X,et al.Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice[J].Cell Transplant,2013,22(6):977-991.
[16]Tsai LK,Wang Z,Munasinghe J,et al.Mesenchymal stem cells primed with valproate and lithium robustly migrate to infarcted regions and facilitate recovery in a stroke model[J].Stroke,2011,42(10):2932-2939.
[17]Ikeda N,Nonoguchi N,Zhao MZ,et al.Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats[J].Stroke,2005,36(12):2725-2730.
[18]边莉,郭子宽,艾辉胜,等.HGF基因修饰增强间充质干细胞的免疫抑制作用[J].军事医学科学院院刊,2006,30(4):323-328.
[19]Zhao Y,Lai W,Xu Y,et al.Exogenous and endogenous therapeutic effects of combination sodium ferulate and bone marrow stromal cells(BMSCs)treatment enhance neurogenesis after rat focal cerebral ischemia[J].Metab Brain Dis,2013,28(4):655-666.
[20]Lee YS,Chio CC,Chang CP,et al.Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke[J].Mediators Inflamm,2013,2013:512978.
[21]Guan Y,Zhao YH.Treatment of cerebral ischemia with combination of bone marrow-derived mesenchymal stem cells and Chinese medicine[J].Chin J Integr Med,2011,17(9):715-720.
[22]Zhang GW,Gu TX,Sun XJ,et al.Edaravone promotes activation of resident cardiac stem cells by transplanted mesenchymal stem cells in a rat myocardial infarction model[J].J Thorac Cardiovasc Surg,2016,152(2):570-582.
[23]Tari K,Atashi A,Kaviani S,et al.Erythropoietin induces production of hepatocyte growth factor from bone marrow mesenchymal stem cells in vitro[J].Biologicals,2017,45:15-19.
[24]Lu H,Wu X,Wang Z,et al.Erythropoietin-activated mesenchymal stem cells promote healing ulcers by improving microenvironment[J].J Surg Res,2016,205(2):464-473.
[25]Fuseler JW,Valarmathi MT.Nitric oxide modulates postnatal bone marrow-derived mesenchymal stem cell migration[J].Front Cell Dev Biol,2016,4:133.
[26]Bulte JW.In vivo MRI cell tracking:clinical studies[J].Am J Roentgenol,2009,193(2):314-325.
[27]Wolfs E,Verfaillie CM,Van Laere K,et al.Radiolabeling strategies for radionuclide imaging of stem cells[J].Stem Cell Rev,2015,11(2):254-274.
[28]Vandsburger MH,Radoul M,Cohen B,et al.MRI Reporter genes:applications for imaging of cell survival,proliferation,migration and differentiation[J].NMR Biomed,2013,26(7):872-884.
[29]Gu E,Chen WY,Gu J,et al.Molecular imaging of stem cells:tracking survival,biodistribution,tumorigenicity,and immunogenicity[J].Theranostics,2012,2(4):335-345.
[30]Tang Y,Zhang C,Wang J,et al.MRI/SPECT/Fluorescent trimodal probe for evaluating the homing and therapeutic efficacy of transplanted mesenchymal stem cells in a rat ischemic stroke model[J].Adv Funct Mater,2015,25(7):1024-1034.
[31]Scheller A,Vivien D,Kirchhoff F,et al.Imaging neuroinflammation after brain injuries by ultrasensitive MRI and two-photon laser-scanning microscopy[J].Rom J Morphol Embryol,2014,55(3):735-743.
[32]Zhang X,Li CX.Arterial spin labeling perfusion magnetic resonance imaging of non-human primates[J].Quant Imaging Med Surg,2016,6(5):573-581.
[33]Raval AP,Saul I,Dave KR,et al.Pretreatment with a single estradiol-17βbolus activates cyclic-AMP response element binding protein and protects CA1 neurons against global cerebral ischemia[J].Neuroscience,2009,160(2):307-318.
[34]Amariglio N,Hirshberg A,Scheithauer BW,et al.Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient[J].PLo S Med,2009,6(2):e1000029.
[35]Tang G,Liu Y,Zhang Z,et al.Mesenchymal stem cells maintain blood-brain barrier integrity by inhibiting aquaporin-4 upregulation after cerebral ischemia[J].Stem Cells,2014,32(12):3150-3162.