余红,朱锦云,王建安

• 1:浙江大学医学院附属第二医院心内科

摘要(Abstract)：

<正>缺血性心肌病,因心肌长期缺血导致心肌纤维化,常伴心律失常和心力衰竭的发生,具有较高的病死率。目前,临床上采用药物、介入手术等方法进行治疗,虽然能减缓疾病进展,改善心脏功能,但因心肌细胞缺血坏死,预后大多不良。虽然有不少证据表明心脏受损伤后心肌细胞更新的速率会增快,但这种反应较轻微且增殖的细胞不足以代替缺失的心肌细胞数,仍会导致心力衰竭的发生。随着对干细胞基础及临床研究的日益深入及干细胞研究技术的成熟,近年来

关键词(KeyWords)： 干细胞治疗;缺血性心肌病;干细胞类型;作用机制

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 余红,朱锦云,王建安

参考文献(References)：

• [1]van Ramshorst J,Rodrigo SF,Schalij MJ,et al.Bone marrow cell injection for chronic myocardial ischemia:the past and the future.J Cardiovasc Transl Res,2011,4:182-191.
• [2]Hare JM,Fishman JE,Gerstenblith G,et al.Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy:the POSEIDON randomized trial.JAMA,2012,308:2369-2379.
• [3]Bartunek J,Behfar A,Dolatabadi D,et al.Cardiopoietic stem cell therapy in heart failure:the C-CURE(Cardiopoietic stem Cell therapy in heart fail URE)multicenter randomized trial with lineage-specified biologics.J Am Coll Cardiol,2013,61:2329-2338.
• [4]Heldman AW,Di Fede DL,Fishman JE,et al.Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy:the TAC-HFT randomized trial.JAMA,2014,311:62-73.
• [5]王建安,谢小洁,孙勇,等.骨髓间质干细胞冠脉内移植治疗近期陈旧性心肌梗死伴心功能不全.中华急诊医学杂志,2005,14:996-999.
• [6]Wollert KC,Meyer GP,Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction:the BOOST randomised controlled clinical trial.Lancet,2004,364:141-148.
• [7]Assmus B,Rolf A,Erbs S,et al.Clinical outcome 2 years after intracoronary administration of bonemarrow-derived progenitorcells in acutemyocardial infarction.Circ Heart Fail,2010,3:89-96.
• [8]Traverse JH,Henry TD,Pepine CJ,et al.Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction:the TIME randomized trial.JAMA,2012,308:2380-2389.
• [9]Traverse JH,Henry TD,Ellis SG,et al.Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3weeks following acute myocardial infarction on left ventricular function:the Late TIME randomized trial.JAMA,2011,306:2110-2119.
• [10]Lunde K,Solheim S,Aakhus S,et al.Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.N Engl J Med,2006,355:1199-1209.
• [11]Perin EC,Willerson JT,Pepine CJ,et al.Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity,left ventricular function,and perfusion in chronic heart failure:the FOCUS-CCTRN trial.JAMA,2012,307:1717-1726.
• [12]Assmus B,Fischer-Rasokat U,Honold J,et al.Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure:results ofmthe TOPCARE-CHD Registry.Circ Res,2007,100:1234-1241.
• [13]Tse HF,Thambar S,Kwong YL,et al.Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases(PROTECT-CAD trial).Eur Heart J,2007,28:2998-3005.
• [14]Huikuri HV,Kervinen K,Niemel?M,et al.Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function,arrhythmia risk profile,and restenosis after thrombolytic therapy of acute myocardial infarction.Eur Heart J,2008,29:2723-2732.
• [15]Hirsch A,Nijveldt R,van der Vleuten PA,et al.Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention:results of the randomized controlled HEBE trial.Eur Heart J,2011,32:1736-1747.
• [16]Perin EC,Silva GV,Henry TD,et al.A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure(FOCUSHF).Am Heart J,2011,161:1078-1087.
• [17]Mathiasen AB,Jrgensen E,Qayyum AA,et al.Rationale and design of the first randomized,double-blind,placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal,Stromal Cells in chronic ischemic Heart Failure(MSC-HF Trial).Am Heart J,2012,164:285-291.
• [18]Bolli R,Chugh AR,D'Amario D,et al.Cardiac stem cells in patients with ischaemic cardiomyopathy(SCIPIO):initial results of a randomised phase 1 trial.Lancet,2011,378:1847-1857.
• [19]Makkar RR,Smith RR,Cheng K,et al.Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction(CADUCEUS):a prospective,randomised phase 1trial.Lancet,2012,379:895-904.
• [20]Bergmann O,Bhardwaj,RD,Bernard S,et al.Evidence for cardiomyocyte renewal in humans.Science,2009,324:98-102.
• [21]Ellison GM,Vicinanza C,Smith AJ,et al.Adult c-kit(pos)cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair.Cell,2013,154:827-842.
• [22]van Berlo JH,Kanisicak O,Maillet M,et al.c-kit+cells minimally contribute cardiomyocytes to the heart.Nature,2014,509:337-341.
• [23]Ye J,Boyle A,Shih H,et al.Sca-1+cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.PLo S One,2012,7:e30329.
• [24]Laugwitz KL,Moretti A,Lam J,et al.Postnatal isl1+cardioblasts enter fully differentiated cardiomyocyte lineages.Nature,2005,433:647-653.
• [25]Chong JJ,Yang X,Don CW,et al.Human embryonic-stem-cellderived cardiomyocytes regenerate non-human primate hearts.Nature,2014,510:273-277.
• [26]Glass C,Singla DK.Overexpression of TIMP-1 in embryonic stem cells attenuates adverse cardiac remodeling following myocardial infarction.Cell Transplant,2012,21:1931-1944.
• [27]Zwi-Dantsis L,Huber I,Habib M,et al.Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients.Eur Heart J,2013,34:1575-1586.
• [28]Savla JJ,Nelson BC,Perry CN,et al.Induced pluripotent stem cells for the study of cardiovascular disease.J Am Coll Cardiol,2014,64:512-519.
• [29]Ieda M,Fu JD,Delgado-Olguin P,et al.Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors.Cell,2010,142:375-386.
• [30]Song K,Nam YJ,Luo X,et al.Heart repair by reprogramming non-myocytes with cardiac transcription factors.Nature,2012,485:599-604.
• [31]Toma C,Pittenger MF,Cahill KS,et al.Human mesenchymal stem cells differentiate to a cardiom yocyte phenotype in the adult murine heart.Circulation,2002,105:93-98.
• [32]D'Amario D,Cabral-Da-Silva MC,Zheng H,et al.Insulin-like growth factor-1 receptor identifies a pool of human cardiac stem cells with superior therapeutic potential for myocardial regeneration.Circ Res,2011,108:1467-1481.
• [33]Guo J,Jie W,Shen Z,et al.SCF increases cardiac stem cell migration through PI3K/AKT and MMP-2/-9 signaling.Int J Mol Med,2014,34:112-118.
• [34]Zacchigna S,Giacca M.Extra-and intracellular factors regulating cardiomyocyte proliferation in postnatal life.Cardiovasc Res,2014,102:312-320.
• [35]Lai RC,Chen TS,Lim SK.Mesenchymal stem cell exosome:a novel stem cell-based therapy for cardiovascular disease.Regen Med,2011,6:481-492.
• [36]Wen Z,Zheng S,Zhou C,et al.Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction.J Cell Mol Med,2011,15:1032-1043.
• [37]Kobayashi T,Hamano K,Li TS,et al.Enhancement of angiogenes is by the implantation of self bone marrow cells in a rat ischemic heart model.J Surg Res,2000,89:189-195
• [38]Zhang Z,Wang JA,Xu Y,et al.Menstrual blood derived mesenchymal cells ameliorate cardiac fibrosis via inhibition of endothelial to mesenchymal transition in myocardial infarction.Int J Cardiol,2013,168:1711-1714.
• [39]Guo S,Cheng Y,Ma Y,et al.Endothelial progenitor cells derived from CD34+cells form cooperative vascular networks.Cell Physiol Biochem,2010,26:679-688.
• [40]Fang J,Chen L,Fan L,et al.Enhanced therapeutic effects of mesenchymal stem cells on myocardial infarction by ischemic postconditioning through paracrine mechanisms in rats.J Mol Cell Cardiol,2011,51:839-847.
• [41]Di Trapani M,Bassi G,Ricciardi M,et al.Comparative study of immune regulatory properties of stem cells derived from different tissues.Stem Cells Dev,2013,22:2990-3002.
• [42]Hu X,Wu R,Jiang Z,et al.Leptin signaling is required for augmented therapeutic properties of mesenchymal stem cells conferred by hypoxia preconditioning.Stem cells,2014,32:2702-2713.
• [43]Fu JD,Stone NR,Liu L,et al.Direct reprogramming of human fibroblasts toward a cardiomyocyte-like State.Stem Cell Reports,2013,1:235-247.