Research Progress in Cell Transplantation for Treatment of Myocardial Infarction_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

 HOUJiang-long ,  WUZhong

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

HOUJiang-long, Email: houjl@163.com; WUZhong, Email: wuzhong71@163.com

Keywords：

Myocardial infarction; Cell transplantation; Regeneration

DOI：

10.7507/1007-4848.20150126

Video：

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Abstract Full text Figures/Tables Video References Cited by

The capacity for self-regeneration of the adult heart is very limited, conventional therapies cannot solve the loss of cardiomyocytes in the infarcted heart leads to continuous ventricular remodeling. Cell transplantation therapy is emerging as a novel approach for myocardial repair over conventional therapies. Various types of cell transplantation have improved cardiac function and angiogenesis in animal models and clinical settings. The safety and feasibility of some clinical trials have been initiated. In this review, we summarize the advantages and limitations of different cell types proposed for cell transplantation in myocardial infarction and give an overview of the clinical trials using this novel therapeutic approach in patients with myocardial infarction.

Citation： HOUJiang-long, WUZhong. Research Progress in Cell Transplantation for Treatment of Myocardial Infarction. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2015, 22(5): 486-490. doi: 10.7507/1007-4848.20150126 Copy

1.	Ye L, Chang YH, Xiong Q, et al. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell, 2014, 15(6):750-761.
2.	Murry CE, Whitney ML, Laflamme MA, et al. Cellular therapies for myocardial infarct repair. Cold Spring Harb Symp Quant Biol, 2002, 67:519-526.
3.	Muller-Ehmsen J, Peterson KL, Kedes L, et al. Rebuilding a damaged heart:long-term survival of transplanted neonatal rat cardiomyocytes after myocardial infarction and effect on cardiac function. Circulation, 2002, 105(14):1720-1726.
4.	Etzion S, Battler A, Barbash IM, et al. Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. J Mol Cell Cardiol, 2001, 33(7):1321-1330.
5.	Koh GY, Klug MG, Soonpaa MH, et al. Differentiation and longterm survival of C2C12 myoblast grafs in heart. J Clin Invest, 1993, 92(3):1548-1554.
6.	Zhu K, Guo C, Xia Y, et al. Transplantation of novel vascular endothelial growth factor gene delivery system manipulated skeletal myoblasts promote myocardial repair. Int J Cardiol, 2013, 168(3):2622-2631.
7.	Pagani FD, DerSimonian H, Zawadzka A, et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol, 2003, 41(5):879-888.
8.	Shudo Y, Miyagawa S, Ohkura H, et al. Addition of mesenchymal stem cells enhances the therapeutic effects of skeletal myoblast cell-sheet transplantation in a rat ischemic cardiomyopathy model. Tissue Eng Part A, 2014, 20(3-4):728-739.
9.	Kellar RS, Shepherd BR, Larson DF, et al. Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function afer acute infarct. Tissue Eng, 2005, 11(11-12):1678-1687.
10.	Wei F, Wang T, Liu J, et al. The subpopulation of mesenchymal stem cells that differentiate toward cardiomyocytes is cardiac progenitor cells. Exp Cell Res, 2011, 317(18):2661-2670.
11.	Jeevanantham V, Butler M, Saad A, et al. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters:a systematic review and meta-analysis. Circulation, 2012, 126(5):551-568.
12.	Francis DP, Mielewczik M, Zargaran D, et al. Autologous bone marrow-derived stem cell therapy in heart disease:discrepancies and contradictions. Int J Cardiol, 2013, 168(4):3381-3403.
13.	Williams AR, Hare JM. Mesenchymal stem cells:biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res, 2011, 109(8):923-940.
14.	Liu B, Duan CY, Luo CF, et al. Effectiveness and safety of selected bone marrow stem cells on left ventricular function in patients with acute myocardial infarction:A meta-analysis of randomized controlled trials. Int J Cardiol, 2014, 177(3):764-770.
15.	Emmert MY, Weber B, Wolint P, et al. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model:a proof of concept study. Plos One, 2013, 8(3):e57759.
16.	Schuleri KH, Feigenbaum GS, Centola M, et al. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J, 2009, 30(22):2722-2732.
17.	Williams AR, Trachtenberg B, Velazquez DL, et al. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy:functional recovery and reverse remodeling. Circ Res, 2011, 108(7):792-796.
18.	Behfar A, Yamada S, Crespo-Diaz R, et al. Guided cardiopoiesis enhances therapeutic beneft of bone marrow human mesenchymal stem cells in chronic myocardial infarction. J Am Coll Cardiol, 2010, 56(9):721-734.
19.	Kawamoto A, Iwasaki H, Kusano K, et al. CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization afer myocardial infarction compared with total mononuclear cells. Circulation, 2006, 114(20):2163-2169.
20.	Losordo DW, Schatz RA, White CJ, et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina:a phase I/Ⅱa double-blind, randomized controlled trial. Circulation, 2007, 115(25):3165-3172.
21.	Stamm C, Kleine HD, Choi YH, et al. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafing for chronic ischemic heart disease:safety and efcacy studies. J Torac Cardiovasc Surg, 2007, 133(3):717-725.
22.	Yerebakan C, Kaminski A, Westphal B, et al. Impact of preoperative lef ventricular function and time from infarction on the long-term benefits after intramyocardial CD133(+) bone marrow stem cell transplant. J Torac Cardiovasc Surg, 2011, 142(6):1530-1539.
23.	Balsam LB, Wagers AJ, Christensen JL, et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 2004, 428(6983):668-673.
24.	Zhu Y, Liu T, Song K, et al. Collagen-chitosan polymer as a scaffold for the proliferation of human adipose tissue-derived stem cells. J Mater Sci Mater Med, 2009, 20(3):799-808.
25.	Paul A, Srivastava S, Chen G, et al. Functional assessment of adipose stem cells for xenotransplantation using myocardial infarction immunocompetent models:comparison with bone marrow stem cells. Cell Biochem Biophys, 2013, 67(2):263-273.
26.	Emmert MY, Emmert LS, Martens A, et al. Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium. Eur Heart J, 2013, 34(36):2830-2838.
27.	Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res, 2004, 95(9):911-921.
28.	Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 2003, 114(6):763-776.
29.	Laugwitz KL, Moretti A, Lam J, et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 2005, 433(7026):647-653.
30.	Makkar RR, Smith RR, Cheng K, et al. Intracoronary cardiospherederived cells for heart regeneration after myocardial infarction (CADUCEUS):a prospective, randomised phase 1 trial. Lancet, 2012, 379(9819):895-904.
31.	Klug MG, Soonpaa MH, Koh GY, et al. Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafs. J Clin Invest, 1996, 98(1):216-224.
32.	Laflamme MA, Chen KY, Naumova AV, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol, 2007, 25(9):1015-1024.
33.	Park IH, Zhao R, West JA, et al. Reprogramming of human somatic cells to pluripotency with defned factors. Nature, 2008, 451(7175):141-146.
34.	Iglesias-Garcia O, Pelacho B, Prosper F. Induced pluripotent stem cells as a new strategy for cardiac regeneration and disease modeling. J Mol Cell Cardiol, 2013, 62:43-50.
35.	Chong JJ, Murry CE. Cardiac regeneration using pluripotent stem cells——Progression to large animal models. Stem Cell Res, 2014, 13(3PB):654-665.
36.	Kawamura M, Miyagawa S, Miki K, et al. Feasibility, safety, and therapeutic efcacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation, 2012, 126(11 Suppl 1):S29-S37.
37.	Kim D, Kim CH, Moon JI, et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 2009, 4(6):472-476.
38.	Lister R, Pelizzola M, Kida YS, et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature, 2011, 471(7336):68-73.
39.	Qian L, Huang Y, Spencer CI, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature, 2012, 485(7400):593-598.
40.	Muraoka N, Ieda M. Direct reprogramming of fibroblasts into myocytes to reverse fbrosis. Annu Rev Physiol, 2014, 76:21-37.

1. Ye L, Chang YH, Xiong Q, et al. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell, 2014, 15(6):750-761.
2. Murry CE, Whitney ML, Laflamme MA, et al. Cellular therapies for myocardial infarct repair. Cold Spring Harb Symp Quant Biol, 2002, 67:519-526.
3. Muller-Ehmsen J, Peterson KL, Kedes L, et al. Rebuilding a damaged heart:long-term survival of transplanted neonatal rat cardiomyocytes after myocardial infarction and effect on cardiac function. Circulation, 2002, 105(14):1720-1726.
4. Etzion S, Battler A, Barbash IM, et al. Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. J Mol Cell Cardiol, 2001, 33(7):1321-1330.
5. Koh GY, Klug MG, Soonpaa MH, et al. Differentiation and longterm survival of C2C12 myoblast grafs in heart. J Clin Invest, 1993, 92(3):1548-1554.
6. Zhu K, Guo C, Xia Y, et al. Transplantation of novel vascular endothelial growth factor gene delivery system manipulated skeletal myoblasts promote myocardial repair. Int J Cardiol, 2013, 168(3):2622-2631.
7. Pagani FD, DerSimonian H, Zawadzka A, et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol, 2003, 41(5):879-888.
8. Shudo Y, Miyagawa S, Ohkura H, et al. Addition of mesenchymal stem cells enhances the therapeutic effects of skeletal myoblast cell-sheet transplantation in a rat ischemic cardiomyopathy model. Tissue Eng Part A, 2014, 20(3-4):728-739.
9. Kellar RS, Shepherd BR, Larson DF, et al. Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function afer acute infarct. Tissue Eng, 2005, 11(11-12):1678-1687.
10. Wei F, Wang T, Liu J, et al. The subpopulation of mesenchymal stem cells that differentiate toward cardiomyocytes is cardiac progenitor cells. Exp Cell Res, 2011, 317(18):2661-2670.
11. Jeevanantham V, Butler M, Saad A, et al. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters:a systematic review and meta-analysis. Circulation, 2012, 126(5):551-568.
12. Francis DP, Mielewczik M, Zargaran D, et al. Autologous bone marrow-derived stem cell therapy in heart disease:discrepancies and contradictions. Int J Cardiol, 2013, 168(4):3381-3403.
13. Williams AR, Hare JM. Mesenchymal stem cells:biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res, 2011, 109(8):923-940.
14. Liu B, Duan CY, Luo CF, et al. Effectiveness and safety of selected bone marrow stem cells on left ventricular function in patients with acute myocardial infarction:A meta-analysis of randomized controlled trials. Int J Cardiol, 2014, 177(3):764-770.
15. Emmert MY, Weber B, Wolint P, et al. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model:a proof of concept study. Plos One, 2013, 8(3):e57759.
16. Schuleri KH, Feigenbaum GS, Centola M, et al. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J, 2009, 30(22):2722-2732.
17. Williams AR, Trachtenberg B, Velazquez DL, et al. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy:functional recovery and reverse remodeling. Circ Res, 2011, 108(7):792-796.
18. Behfar A, Yamada S, Crespo-Diaz R, et al. Guided cardiopoiesis enhances therapeutic beneft of bone marrow human mesenchymal stem cells in chronic myocardial infarction. J Am Coll Cardiol, 2010, 56(9):721-734.
19. Kawamoto A, Iwasaki H, Kusano K, et al. CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization afer myocardial infarction compared with total mononuclear cells. Circulation, 2006, 114(20):2163-2169.
20. Losordo DW, Schatz RA, White CJ, et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina:a phase I/Ⅱa double-blind, randomized controlled trial. Circulation, 2007, 115(25):3165-3172.
21. Stamm C, Kleine HD, Choi YH, et al. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafing for chronic ischemic heart disease:safety and efcacy studies. J Torac Cardiovasc Surg, 2007, 133(3):717-725.
22. Yerebakan C, Kaminski A, Westphal B, et al. Impact of preoperative lef ventricular function and time from infarction on the long-term benefits after intramyocardial CD133(+) bone marrow stem cell transplant. J Torac Cardiovasc Surg, 2011, 142(6):1530-1539.
23. Balsam LB, Wagers AJ, Christensen JL, et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 2004, 428(6983):668-673.
24. Zhu Y, Liu T, Song K, et al. Collagen-chitosan polymer as a scaffold for the proliferation of human adipose tissue-derived stem cells. J Mater Sci Mater Med, 2009, 20(3):799-808.
25. Paul A, Srivastava S, Chen G, et al. Functional assessment of adipose stem cells for xenotransplantation using myocardial infarction immunocompetent models:comparison with bone marrow stem cells. Cell Biochem Biophys, 2013, 67(2):263-273.
26. Emmert MY, Emmert LS, Martens A, et al. Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium. Eur Heart J, 2013, 34(36):2830-2838.
27. Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res, 2004, 95(9):911-921.
28. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 2003, 114(6):763-776.
29. Laugwitz KL, Moretti A, Lam J, et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 2005, 433(7026):647-653.
30. Makkar RR, Smith RR, Cheng K, et al. Intracoronary cardiospherederived cells for heart regeneration after myocardial infarction (CADUCEUS):a prospective, randomised phase 1 trial. Lancet, 2012, 379(9819):895-904.
31. Klug MG, Soonpaa MH, Koh GY, et al. Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafs. J Clin Invest, 1996, 98(1):216-224.
32. Laflamme MA, Chen KY, Naumova AV, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol, 2007, 25(9):1015-1024.
33. Park IH, Zhao R, West JA, et al. Reprogramming of human somatic cells to pluripotency with defned factors. Nature, 2008, 451(7175):141-146.
34. Iglesias-Garcia O, Pelacho B, Prosper F. Induced pluripotent stem cells as a new strategy for cardiac regeneration and disease modeling. J Mol Cell Cardiol, 2013, 62:43-50.
35. Chong JJ, Murry CE. Cardiac regeneration using pluripotent stem cells——Progression to large animal models. Stem Cell Res, 2014, 13(3PB):654-665.
36. Kawamura M, Miyagawa S, Miki K, et al. Feasibility, safety, and therapeutic efcacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation, 2012, 126(11 Suppl 1):S29-S37.
37. Kim D, Kim CH, Moon JI, et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 2009, 4(6):472-476.
38. Lister R, Pelizzola M, Kida YS, et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature, 2011, 471(7336):68-73.
39. Qian L, Huang Y, Spencer CI, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature, 2012, 485(7400):593-598.
40. Muraoka N, Ieda M. Direct reprogramming of fibroblasts into myocytes to reverse fbrosis. Annu Rev Physiol, 2014, 76:21-37.

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Research Progress in Cell Transplantation for Treatment of Myocardial Infarction

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