From bench to bedside, work in cell-based myocardial regeneration therapy

DOI: 10.4236/jbise.2014.72012   PDF   HTML     4,204 Downloads   5,604 Views   Citations


In clinical cellular cardiomyoplasty, bone marrow cells and myoblasts are introduced mainly to ischemic cardiomyopathy tissue via several cell delivery systems, such as needle injection or catheter. These clinical studies have demonstrated the safety and feasibility of this technique, but its effectiveness for treating heart failure, especially in the long term, is still under discussion. Neither of these cell types can differentiate into cardiomyocytes; rather, they improve the failing heart mainly by the paracrine effects of some cytokines, such as Hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF). Thus, many researchers have a great interest in stem cells, which exist in bone marrow, circulating blood, atrium, and adipose tissue, and can differentiate into cardiomyocytes. Although several stem cells with the potential to differentiate into various cell types have been reported, few can differentiate into cardiomyocytes. Moreover, beating cells that can demonstrate synchronized contraction with native cardiomyocytes are critical for the complete repair of severe heart failure. Therefore, stem cells with a high differentiation capacity should be explored for the goal of completely repairing severely damaged myocardium. In this review, we summarize the clinical protocols and basic experiments for cellular cardiomyoplasty using bone marrow cells, myoblasts, and other stem cells.

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Miyagawa, S. and Sawa, Y. (2014) From bench to bedside, work in cell-based myocardial regeneration therapy. Journal of Biomedical Science and Engineering, 7, 86-103. doi: 10.4236/jbise.2014.72012.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Murry, C.E., Soonpaa, M.H., Reinecke, H., Nakajima, H., Nakajima, H.O., Rubart, M., Pasumarthi, K.B., Virag, J.I., Bartelmez, S.H., Poppa, V., Bradford, G., Dowell, J.D., Williams, D.A. and Field, L.J. (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 428, 664-668.
[2] Memon, I.A., Sawa, Y., Fukushima, N., Matsumiya, G., Miyagawa, S., Taketani, S., Sakakida, S.K., Kondoh, H., Aleshin, A.N., Shimizu, T., Okano, T. and Matsuda, H. (2005) Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets. The Journal of Thoracic and Cardiovascular Surgery, 130, 1333-1341.
[3] Marelli, D., Desrosiers, C., el-Alfy, M., Kao, R.L. and Chiu, R.C. (1992) Cell transplantation for myocardial repair: An experimental approach. Cell Transplantation, 1, 383-390.
[4] Chiu, R.C., Zibaitis, A. and Kao, R.L. (1995) Cellular cardiomyoplasty: Myocardial regeneration with satellite cell implantation. The Annals of Thoracic Surgery, 60, 12-18.
[5] Jain, M., DerSimonian, H., Brenner, D.A., Ngoy, S., Teller, P., Edge, A.S., Zawadzka, A., Wetzel, K., Sawyer, D.B., Colucci, W.S., Apstein, C.S. and Liao, R. (2001) Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction. Circulation, 103, 1920-1927.
[6] Taylor, D.A., Atkins, B.Z., Hungspreugs, P., Jones, T.R., Reedy, M.C., Hutcheson, K.A., Glower, D.D. and Kraus, W.E. (1998) Regenerating functional myocardium: Improved performance after skeletal myoblast transplantation. Nature Medicine, 4, 929-933.
[7] Reinecke, H., Poppa, V. and Murry, C.E. (2002) Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. Journal of Molecular and Cellular Cardiology, 34, 241-249.
[8] Reinecke, H., MacDonald, G.H., Hauschka, S.D. and Murry, C.E. (2000) Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. The Journal of Cell Biology, 149, 731-740.
[9] Reinecke, H., Minami, E., Poppa, V. and Murry, C.E. (2004) Evidence for fusion between cardiac and skeletal muscle cells. Circulation Research, 94, e56-60.
[10] Rubart, M., Soonpaa, M.H., Nakajima, H. and Field, L.J. (2004) Spontaneous and evoked intracellular calcium transients in donor-derived myocytes following intracardiac myoblast transplantation. Journal of Clinical Investigation, 114, 775-783.
[11] Suzuki, K., Brand, N.J., Allen, S., Khan, M.A., Farrell, A.O., Murtuza, B., Oakley, R.E. and Yacoub, M.H. (2001) Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell transplantation to the heart. The Journal of Thoracic and Cardiovascular Surgery, 122, 759-766.
[12] Leobon, B., Garcin, I., Menasche, P., Vilquin, J.T., Audinat, E. and Charpak, S. (2003) Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proceedings of the National Academy of Sciences, 100, 7808-7811.
[13] Menasche, P. (2004) Skeletal myoblast transplantation for cardiac repair. Expert Review of Cardiovascular Therapy—Expert Reviews, 2, 21-28.
[14] Dib, N., Michler, R.E., Pagani, F.D., Wright, S., Kereiakes, D.J., Lengerich, R., Binkley, P., Buchele, D., Anand, I., Swingen, C., Di Carli, M.F., Thomas, J.D., Jaber, W.A., Opie, S.R., Campbell, A., McCarthy, P., Yeager, M., Dilsizian, V., Griffith, B.P., Korn, R., Kreuger, S.K., Ghazoul, M., MacLellan, W.R., Fonarow, G., Eisen, H.J., Dinsmore, J. and Diethrich, E. (2005) Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: Four-year follow-up. Circulation, 112, 1748-1755.
[15] Menasche, P., Hagege, A.A., Vilquin, J.T., Desnos, M., Abergel, E., Pouzet, B., Bel, A., Sarateanu, S., Scorsin, M., Schwartz, K., Bruneval, P., Benbunan, M., Marolleau, J.P. and Duboc, D. (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. Journal of the American College of Cardiology, 41, 1078-1083.
[16] Herreros, J., Prosper, F., Perez, A., Gavira, J.J., Garcia-Velloso, M.J., Barba, J., Sanchez, P.L., Canizo, C., Rabago, G., Marti-Climent, J.M., Hernandez, M., Lopez-Holgado, N., Gonzalez-Santos, J.M., Martin-Luengo, C. and Alegria, E. (2003) Autologous intramyocardial injec- tion of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. European Heart Journal, 24, 2012-2020.
[17] Pagani, F.D., DerSimonian, H., Zawadzka, A., Wetzel, K., Edge, A.S., Jacoby, D.B., Dinsmore, J.H., Wright, S., Aretz, T.H., Eisen, H.J. and Aaronson, K.D. (2003) Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. Journal of the American College of Cardiology, 41, 879-888.
[18] Siminiak, T., Kalawski, R., Fiszer, D., Jerzykowska, O., Rzezniczak, J., Rozwadowska, N. and Kurpisz, M. (2004) Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: Phase I clinical study with 12 months of follow-up. American Heart Journal, 148, 531-537.
[19] Smits, P.C., van Geuns, R.J., Poldermans, D., Bountioukos, M., Onderwater, E.E., Lee, C.H., Maat, A.P. and Serruys, P.W. (2003) Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: Clinical experience with six-month follow-up. Journal of the American College of Cardiology, 42, 2063-2069.
[20] Hagege, A.A., Carrion, C., Menasche, P., Vilquin, J.T., Duboc, D., Marolleau, J.P., Desnos, M. and Bruneval, P. (2003) Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. Lancet, 361, 491-492.
[21] Menasche, P., Alfieri, O., Janssens, S., McKenna, W., Reichenspurner, H., Trinquart, L., Vilquin, J.T., Marolleau, J.P., Seymour, B., Larghero, J., Lake, S., Chatellier, G., Solomon, S., Desnos, M. and Hagege, A.A. (2008) The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation, 117, 1189-1200.
[22] Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E., Stornaiuolo, A., Cossu, G. and Mavilio, F. (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 279, 1528-1530.
[23] Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S.M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D.M., Leri, A. and Anversa, P. (2001) Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701-705.
[24] Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., Nadal-Ginard, B., Bodine, D.M., Leri, A. and Anversa, P. (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proceedings of the National Academy of Sciences, 98, 10344-10349.
[25] Jackson, K.A., Majka, S.M., Wang, H., Pocius, J., Hartley, C.J., Majesky, M.W., Entman, M.L., Michael, L.H., Hirschi, K.K. and Goodell, M.A. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. Journal of Clinical Investigation, 107, 1395-1402.
[26] Balsam, L.B., Wagers, A.J., Christensen, J.L., Kofidis, T., Weissman, I.L. and Robbins, R.C. (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 428, 668-673.
[27] Vassilopoulos, G., Wang, P.R. and Russell, D.W. (2003) Transplanted bone marrow regenerates liver by cell fusion. Nature, 422, 901-904.
[28] Alvarez-Dolado, M., Pardal, R., Garcia-Verdugo, J.M., Fike, J.R., Lee, H.O., Pfeffer, K., Lois, C., Morrison, S.J. and Alvarez-Buylla, A. (2003) Fusion of bone-marrow- derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature, 425, 968-973.
[29] Terada, N., Hamazaki, T., Oka, M., Hoki, M., Mastalerz, D.M., Nakano, Y., Meyer, E.M., Morel, L., Petersen, B.E. and Scott, E.W. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature, 416, 542-545.
[30] Nygren, J.M., Jovinge, S., Breitbach, M., Sawen, P., Roll, W., Hescheler, J., Taneera, J., Fleischmann, B.K. and Jacobsen, S.E. (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nature Medicine, 10, 494-501.
[31] Laflamme, M.A. and Murry, C.E. (2005) Regenerating the heart. Nature Biotechnology, 23, 845-856.
[32] Kajstura, J., Rota, M., Whang, B., Cascapera, S., Hosoda, T., Bearzi, C., Nurzynska, D., Kasahara, H., Zias, E., Bonafe, M., Nadal-Ginard, B., Torella, D., Nascimbene, A., Quaini, F., Urbanek, K., Leri, A. and Anversa, P. (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circulation Research, 96, 127-137.
[33] Yoon, Y.S., Wecker, A., Heyd, L., Park, J.S., Tkebuchava, T., Kusano, K., Hanley, A., Scadova, H., Qin, G., Cha, D.H., Johnson, K.L., Aikawa, R., Asahara, T. and Losordo, D.W. (2005) Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. Journal of Clinical Investigation, 115, 326-338.
[34] Caplan, A.I. and Dennis, J.E. (2006) Mesenchymal stem cells as trophic mediators. Journal of Cellular Biochemistry, 98, 1076-1084.
[35] Bittira, B., Kuang, J.Q., Al-Khaldi, A., Shum-Tim, D. and Chiu, R.C. (2002) In vitro preprogramming of marrow stromal cells for myocardial regeneration. Annals of Thoracic Surgery, 74, 1154-1159, discussion 1159-1160.
[36] Makino, S., Fukuda, K., Miyoshi, S., Konishi, F., Kodama, H., Pan, J., Sano, M., Takahashi, T., Hori, S., Abe, H., Hata, J., Umezawa, A. and Ogawa, S. (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. Journal of Clinical Investigation, 103, 697-705.
[37] Miyahara, Y., Nagaya, N., Kataoka, M., Yanagawa, B., Tanaka, K., Hao, H., Ishino, K., Ishida, H., Shimizu, T., Kangawa, K., Sano, S., Okano, T., Kitamura, S. and Mori, H. (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nature Medicine, 12, 459-465.
[38] Amado, L.C., Saliaris, A.P., Schuleri, K.H., St John, M., Xie, J.S., Cattaneo, S., Durand, D.J., Fitton, T., Kuang, J.Q., Stewart, G., Lehrke, S., Baumgartner, W.W., Martin, B.J., Heldman, A.W. and Hare, J.M. (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America, 102, 11474-11479.
[39] Pittenger, M.F. and Martin, B.J. (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circulation Research, 95, 9-20.
[40] Wollert, K.C., Meyer, G.P., Lotz, J., Ringes-Lichtenberg, S., Lippolt, P., Breidenbach, C., Fichtner, S., Korte, T., Hornig, B., Messinger, D., Arseniev, L., Hertenstein, B., Ganser, A. and Drexler, H. (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: The BOOST randomised controlled clinical trial. Lancet, 364, 141-148.
[41] Meyer, G.P., Wollert, K.C., Lotz, J., Steffens, J., Lippolt, P., Fichtner, S., Hecker, H., Schaefer, A., Arseniev, L., Hertenstein, B., Ganser, A. and Drexler, H. (2006) Intracoronary bone marrow cell transfer after myocardial infarction: Eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation, 113, 1287-1294.
[42] Yousef, M., Schannwell, C.M., Kostering, M., Zeus, T., Brehm, M. and Strauer, B.E. (2009) The BALANCE Study: Clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. Journal of the American College of Cardiology, 53, 2262-2269.
[43] Janssens, S., Dubois, C., Bogaert, J., Theunissen, K., Deroose, C., Desmet, W., Kalantzi, M., Herbots, L., Sinnaeve, P., Dens, J., Maertens, J., Rademakers, F., Dymarkowski, S., Gheysens, O., Van Cleemput, J., Bormans, G., Nuyts, J., Belmans, A., Mortelmans, L., Boogaerts, M. and Van de Werf, F. (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: Double-blind, rando-mised controlled trial. Lancet, 367, 113-121.
[44] Schachinger, V., Erbs, S., Elsasser, A., Haberbosch, W., Hambrecht, R., Holschermann, H., Yu, J., Corti, R., Mathey, D.G., Hamm, C.W., Suselbeck, T., Assmus, B., Tonn, T., Dimmeler, S. and Zeiher, A.M. (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. New England Journal of Medicine, 355, 1210-1221.
[45] Lunde, K., Solheim, S., Aakhus, S., Arnesen, H., Abdelnoor, M., Egeland, T., Endresen, K., Ilebekk, A., Mangschau, A., Fjeld, J.G., Smith, H.J., Taraldsrud, E., Grogaard, H.K., Bjornerheim, R., Brekke, M., Muller, C., Hopp, E., Ragnarsson, A., Brinchmann, J.E. and Forfang, K. (2006) Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. New England Journal of Medicine, 355, 1199-1209.
[46] Perin, E.C., Dohmann, H.F., Borojevic, R., Silva, S.A., Sousa, A.L., Mesquita, C.T., Rossi, M.I., Carvalho, A.C., Dutra, H.S., Dohmann, H.J., Silva, G.V., Belem, L., Vivacqua, R., Rangel, F.O., Esporcatte, R., Geng, Y.J., Vaughn, W.K., Assad, J.A., Mesquita, E.T. and Willerson, J.T. (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation, 107, 2294-2302.
[47] Perin, E.C., Dohmann, H.F., Borojevic, R., Silva, S.A., Sousa, A.L., Silva, G.V., Mesquita, C.T., Belem, L., Vaughn, W.K., Rangel, F.O., Assad, J.A., Carvalho, A.C., Branco, R.V., Rossi, M.I., Dohmann, H.J. and Willerson, J.T. (2004) Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation, 110, II213-II218.
[48] Fuchs, S., Satler, L.F., Kornowski, R., Okubagzi, P., Weisz, G., Baffour, R., Waksman, R., Weissman, N.J., Cerqueira, M., Leon, M.B. and Epstein, S.E. (2003) Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: A feasibility study. Journal of the American College of Cardiology, 41, 1721-1724.
[49] Assmus, B., Honold, J., Schachinger, V., Britten, M.B., Fischer-Rasokat, U., Lehmann, R., Teupe, C., Pistorius, K., Martin, H., Abolmaali, N.D., Tonn, T., Dimmeler, S. and Zeiher, A.M. (2006) Transcoronary transplantation of progenitor cells after myocardial infarction. New England Journal of Medicine, 355, 1222-1232.
[50] Schachinger, V., Assmus, B., Britten, M.B., Honold, J., Lehmann, R., Teupe, C., Abolmaali, N.D., Vogl, T.J., Hofmann, W.K., Martin, H., Dimmeler, S. and Zeiher, A.M. (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: Final one-year results of the TOPCARE-AMI Trial. Journal of the American College of Cardiology, 44, 1690-1699.
[51] Abdel-Latif, A., Bolli, R., Tleyjeh, I.M., Montori, V.M., Perin, E.C., Hornung, C.A., Zuba-Surma, E.K., Al-Mallah, M. and Dawn, B. (2007) Adult bone marrow-derived cells for cardiac repair: A systematic review and meta-analysis. JAMA Internal Medicine, 167, 989-997.
[52] Reffelmann, T., Konemann, S. and Kloner, R.A. (2009) Promise of blood- and bone marrow-derived stem cell transplantation for functional cardiac repair: Putting it in perspective with existing therapy. Journal of the American College of Cardiology, 53, 305-308.
[53] Quirici, N., Soligo, D., Caneva, L., Servida, F., Bossolasco, P. and Deliliers, G.L. (2001) Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. British Journal of Haematology, 115, 186-194.
[54] Stamm, C., Westphal, B., Kleine, H.D., Petzsch, M., Kittner, C., Klinge, H., Schumichen, C., Nienaber, C.A., Freund, M. and Steinhoff, G. (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet, 361, 45-46.
[55] Stamm, C., Kleine, H.D., Choi, Y.H., Dunkelmann, S., Lauffs, J.A., Lorenzen, B., David, A., Liebold, A., Nienaber, C., Zurakowski, D., Freund, M. and Steinhoff, G. (2007) Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: Safety and efficacy studies. Journal of Thoracic and Cardiovascular Surgery, 133, 717-725.
[56] Bartunek, J., Vanderheyden, M., Vandekerckhove, B., Mansour, S., De Bruyne, B., De Bondt, P., Van Haute, I., Lootens, N., Heyndrickx, G. and Wijns, W. (2005) Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: Feasibility and safety. Circulation, 112, I178-I183.
[57] Losordo, D.W., Schatz, R.A., White, C.J., Udelson, J.E., Veereshwarayya, V., Durgin, M., Poh, K.K., Weinstein, R., Kearney, M., Chaudhry, M., Burg, A., Eaton, L., Heyd, L., Thorne, T., Shturman, L., Hoffmeister, P., Story, K., Zak, V., Dowling, D., Traverse, J.H., Olson, R.E., Flanagan, J., Sodano, D., Murayama, T., Kawamoto, A., Kusano, K.F., Wollins, J., Welt, F., Shah, P., Soukas, P., Asahara, T. and Henry, T.D. (2007) Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: A phase I/IIa double-blind, randomized controlled trial. Circulation, 115, 3165-3172.
[58] Chen, S., Liu, Z., Tian, N., Zhang, J., Yei, F., Duan, B., Zhu, Z., Lin, S. and Kwan, T.W. (2006) Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. Journal of Invasive Cardiology, 18, 552-556.
[59] Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G. and Isner, J.M. (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275, 964-966.
[60] Iwasaki, H., Kawamoto, A., Ishikawa, M., Oyamada, A., Nakamori, S., Nishimura, H., Sadamoto, K., Horii, M., Matsumoto, T., Murasawa, S., Shibata, T., Suehiro, S. and Asahara, T. (2006) Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction. Circulation, 113, 1311-1325.
[61] Tatsumi, T., Ashihara, E., Yasui, T., Matsunaga, S., Kido, A., Sasada, Y., Nishikawa, S., Hadase, M., Koide, M., Nakamura, R., Irie, H., Ito, K., Matsui, A., Matsui, H., Katamura, M., Kusuoka, S., Matoba, S., Okayama, S., Horii, M., Uemura, S., Shimazaki, C., Tsuji, H., Saito, Y. and Matsubara, H. (2007) Intracoronary transplantation of non-expanded peripheral blood-derived mononuclear cells promotes improvement of cardiac function in patients with acute myocardial infarction. Circulation Journal, 71, 1199-1207.
[62] Erbs, S., Linke, A., Adams, V., Lenk, K., Thiele, H., Diederich, K.W., Emmrich, F., Kluge, R., Kendziorra, K., Sabri, O., Schuler, G. and Hambrecht, R. (2005) Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: First randomized and placebo-controlled study. Circulation Research, 97, 756-762.
[63] Kang, H.J., Lee, H.Y., Na, S.H., Chang, S.A., Park, K.W., Kim, H.K., Kim, S.Y., Chang, H.J., Lee, W., Kang, W.J., Koo, B.K., Kim, Y.J., Lee, D.S., Sohn, D.W., Han, K.S., Oh, B.H., Park, Y.B. and Kim, H.S. (2006) Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: The MAGIC Cell-3-DES randomized, controlled trial. Circulation, 114, I145-I151.
[64] Katritsis, D.G., Sotiropoulou, P.A., Karvouni, E., Karabinos, I., Korovesis, S., Perez, S.A., Voridis, E.M. and Papamichail, M. (2005) Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheterization and Cardiovascular Interventions, 65, 321-329.
[65] Miyagawa, S., Matsumiya, G., Funatsu, T., Yoshitatsu, M., Sekiya, N., Fukui, S., Hoashi, T., Hori, M., Yoshikawa, H., Kanakura, Y., Ishikawa, J., Aozasa, K., Kawaguchi, N., Matsuura, N., Myoui, A., Matsuyama, A., Ezoe, S., Iida, H., Matsuda, H. and Sawa, Y. (2009) Combined autologous cellular cardiomyoplasty using skeletal myoblasts and bone marrow cells for human ischemic cardiomyopathy with left ventricular assist system implantation: Report of a case. Surgery Today, 39, 133-136.
[66] Memon, I.A., Sawa, Y., Miyagawa, S., Taketani, S. and Matsuda, H. (2005) Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy. Journal of Thoracic and Cardiovascular Surgery, 130, 646-653.
[67] Takahashi, M., Li, T.S., Suzuki, R., Kobayashi, T., Ito, H., Ikeda, Y., Matsuzaki, M. and Hamano, K. (2006) Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury. American Journal of Physiology-Heart and Circulatory Physiology, 291, H886-H893.
[68] Uemura, R., Xu, M., Ahmad, N. and Ashraf, M. (2006) Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circulation Research, 98, 1414-1421.
[69] Kamihata, H., Matsubara, H., Nishiue, T., Fujiyama, S., Tsutsumi, Y., Ozono, R., Masaki, H., Mori, Y., Iba, O., Tateishi, E., Kosaki, A., Shintani, S., Murohara, T., Imaizumi, T. and Iwasaka, T. (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation, 104, 1046-1052.
[70] Kinnaird, T., Stabile, E., Burnett, M.S., Shou, M., Lee, C.W., Barr, S., Fuchs, S. and Epstein, S.E. (2004) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation, 109, 1543-1549.
[71] Kinnaird, T., Stabile, E., Burnett, M.S., Lee, C.W., Barr, S., Fuchs, S. and Epstein, S.E. (2004) Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circulation Research, 94, 678-685.
[72] Askari, A.T., Unzek, S., Popovic, Z.B., Goldman, C.K., Forudi, F., Kiedrowski, M., Rovner, A., Ellis, S.G., Thomas, J.D., DiCorleto, P.E., Topol, E.J. and Penn, M.S. (2003) Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet, 362, 697-703.
[73] Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J.M. and Asahara, T. (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nature Medicine, 5, 434-438.
[74] Misao, Y., Takemura, G., Arai, M., Ohno, T., Onogi, H., Takahashi, T., Minatoguchi, S., Fujiwara, T. and Fujiwara, H. (2006) Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-CSF. Cardiovascular Research, 71, 455-465.
[75] Klyushnenkova, E., Mosca, J.D., Zernetkina, V., Majumdar, M.K., Beggs, K.J., Simonetti, D.W., Deans, R.J. and McIntosh, K.R. (2005) T cell responses to allogeneic human mesenchymal stem cells: Immunogenicity, tolerance, and suppression. Journal of Biomedical Science, 12, 47-57.
[76] Imanishi, Y., Saito, A., Komoda, H., Kitagawa-Sakakida, S., Miyagawa, S., Kondoh, H., Ichikawa, H. and Sawa, Y. (2008) Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute myocardial infarction in rats. Journal of Molecular and Cellular Cardiology, 44, 662-671.
[77] Oh, H., Bradfute, S.B., Gallardo, T.D., Nakamura, T., Gaussin, V., Mishina, Y., Pocius, J., Michael, L.H., Behringer, R.R., Garry, D.J., Entman, M.L. and Schneider, M.D. (2003) Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences of the United States of America, 100, 12313-12318.
[78] Chiavegato, A., Bollini, S., Pozzobon, M., Callegari, A., Gasparotto, L., Taiani, J., Piccoli, M., Lenzini, E., Gerosa, G., Vendramin, I., Cozzi, E., Angelini, A., Iop, L., Zanon, G.F., Atala, A., De Coppi, P. and Sartore, S. (2007) Human amniotic fluid-derived stem cells are rejected after transplantation in the myocardium of normal, ischemic, immuno-suppressed or immuno-deficient rat. Journal of Molecular and Cellular Cardiology, 42, 746-759.
[79] Nakagami, H., Morishita, R., Maeda, K., Kikuchi, Y., Ogihara, T. and Kaneda, Y. (2006) Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. Journal of Atherosclerosis and Thrombosis, 13, 77-81.
[80] Messina, E., De Angelis, L., Frati, G., Morrone, S., Chimenti, S., Fiordaliso, F., Salio, M., Battaglia, M., Latronico, M.V., Coletta, M., Vivarelli, E., Frati, L., Cossu, G. and Giacomello, A. (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation Research, 95, 911-921.
[81] Toma, C., Pittenger, M.F., Cahill, K.S., Byrne, B.J. and Kessler, P.D. (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation, 105, 93-98.
[82] Evans, M.J. and Kaufman, M.H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature, 292, 154-156.
[83] Bel, A., Planat-Bernard, V., Saito, A., Bonnevie, L., Bellamy, V., Sabbah, L., Bellabas, L., Brinon, B., Vanneaux, V., Pradeau, P., Peyrard, S., Larghero, J., Pouly, J., Binder, P., Garcia, S., Shimizu, T., Sawa, Y., Okano, T., Bruneval, P., Desnos, M., Hagege, A.A., Casteilla, L., Puceat, M. and Menasche, P. (2010) Composite cell sheets: A further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells. Circulation, 122, S118-S123.
[84] Takahashi, K. and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663-676.
[85] Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., Slukvin, I.I. and Thomson, J.A. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917-1920.
[86] Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. and Yamanaka, S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861-872.
[87] Hattori, F., Chen, H., Yamashita, H., Tohyama, S., Satoh, Y.S., Yuasa, S., Li, W., Yamakawa, H., Tanaka, T., Onitsuka, T., Shimoji, K., Ohno, Y., Egashira, T., Kaneda, R., Murata, M., Hidaka, K., Morisaki, T., Sasaki, E., Suzuki, T., Sano, M., Makino, S., Oikawa, S. and Fukuda, K. (2009) Nongenetic method for purifying stem cell-derived cardiomyocytes. Nature Methods, 7, 61-66.
[88] Seki, T., Yuasa, S., Oda, M., Egashira, T., Yae, K., Kusumoto, D., Nakata, H., Tohyama, S., Hashimoto, H., Kodaira, M., Okada, Y., Seimiya, H., Fusaki, N., Hasegawa, M. and Fukuda, K. (2010) Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell, 7, 11-14.
[89] Miyagawa, S., Roth, M., Saito, A., Sawa, Y. and Kostin, S. (2011) Tissue-engineered cardiac constructs for cardiac repair. Annals of Thoracic Surgery, 91, 320-329.
[90] Kawamura, M., Miyagawa, S., Miki, K., Saito, A., Fukushima, S., Higuchi, T., Kawamura, T., Kuratani, T., Daimon, T., Shimizu, T., Okano, T. and Sawa, Y. (2012) Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation, 126, S29-S37.
[91] Miki, K., Uenaka, H., Saito, A., Miyagawa S, Sakaguchi, T., Higuchi, T., Shimizu T, Okano, T., Yamanaka, S. and Sawa, Y. (2012) Bioengineered myocardium derived from induced pluripotent stem cells improves cardiac function and attenuates cardiac remodeling following chronic myocardial infarction in rats. Stem Cells Translational Medicine, 1, 430-437.
[92] Ieda, M., Fu, J.D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B.G. and Srivastava, D. (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell, 142, 375-386.
[93] Miyagawa, S., Sawa, Y., Taketani, S., Kawaguchi, N., Nakamura, T., Matsuura, N. and Matsuda, H. (2002) Myocardial regeneration therapy for heart failure: Hepatocyte growth factor enhances the effect of cellular cardiomyoplasty. Circulation, 105, 2556-2561.
[94] Gavira, J.J., Nasarre, E., Abizanda, G., Perez-Ilzarbe, M., de Martino-Rodriguez, A., Garcia de Jalon, J.A., Mazo, M., Macias, A., Garcia-Bolao, I., Pelacho, B., Martinez-Caro, D. and Prosper, F. (2010) Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction. European Heart Journal, 31, 1013-1021.

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