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Abstract: congestive heart failure (CHF) has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout (necrosis and apoptosis) plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells (CSCs) within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells (BMCs) to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animal CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.

[1] Adler, E.D., Maddox, T.M., 2007. Cell therapy for cardiac disease: where do we go from here? Nat. Clin. Pract. Cardiovasc. Med., 4(1):2-3.

[2] 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., et al., 2005. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc. Natl. Acad. Sci. USA, 102(32):11474-11479.

[3] Anversa, P., Sonnenblick, E.H., 1990. Ischemic cardiomyopathy: pathophysiologic mechanisms. Prog. Cardiovasc. Dis., 33(1):49-70.

[4] Anversa, P., Nadal-Ginard, B., 2002. Myocyte renewal and ventricular remodelling. Nature, 415(6868):240-243.

[5] Anversa, P., Li, P., Zhang, X., Olivetti, G., Capasso, J.M., 1993. Ischaemic myocardial injury and ventricular remodelling. Cardiovasc. Res., 27(2):145-157.

[6] Anversa, P., Kajstura, J., Leri, A., Bolli, R., 2006. Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation, 113(11):1451-1463.

[7] Archundia, A., Aceves, J.L., Lopez-Hernandez, M., Alvarado, M., Rodriguez, E., Diaz Quiroz, G., Paez, A., Rojas, F.M., Montano, L.F., 2005. Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction. Life Sci., 78(3):279-283.

[8] Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., Isner, J.M., 1997. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275(5302):964-967.

[9] Assmus, B., Honold, J., Schachinger, V., Britten, M.B., Fischer-Rasokat, U., Lehmann, R., Teupe, C., Pistorius, K., Martin, H., Abolmaali, N.D., et al., 2006. Transcoronary transplantation of progenitor cells after myocardial infarction. N. Engl. J. Med., 355(12):1222-1232.

[10] Balsam, L.B., Wagers, A.J., Christensen, J.L., Kofidis, T., Weissman, I.L., Robbins, R.C., 2004. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 428(6983):668-673.

[11] Barile, L., Chimenti, I., Gaetani, R., Forte, E., Miraldi, F., Frati, G., Messina, E., Giacomello, A., 2007. Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration. Nat. Clin. Pract. Cardiovasc. Med., 4(Suppl. 1):S9-S14.

[12] Bart, B.A., Shaw, L.K., McCants, C.B.Jr, Fortin, D.F., Lee, K.L., Califf, R.M., O'Connor, C.M., 1997. Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. J. Am. Coll. Cardiol., 30(4):1002-1008.

[13] Beltrami, A.P., Urbanek, K., Kajstura, J., Yan, S.M., Finato, N., Bussani, R., Nadal-Ginard, B., Silvestri, F., Leri, A., Beltrami, C.A., et al., 2001. Evidence that human cardiac myocytes divide after myocardial infarction. N. Engl. J. Med., 344(23):1750-1757.

[14] Beltrami, A.P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E., Urbanek, K., et al., 2003. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114(6):763-776.

[15] Capi, O., Gepstein, L., 2006. Myocardial regeneration strategies using human embryonic stem cell-derived cardiomyocytes. J. Control Release, 116(2):211-218.

[16] Chen, S.L., Fang, W.W., Ye, F., Liu, Y.H., Qian, J., Shan, S.J., Zhang, J.J., Chunhua, R.Z., Liao, L.M., Lin, S., et al., 2004. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am. J. Cardiol., 94(1):92-95.

[17] Dai, W., Hale, S.L., Martin, B.J., Kuang, J.Q., Dow, J.S., Wold, L.E., Kloner, R.A., 2005. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation, 112(2):214-223.

[18] Dawn, B., Stein, A.B., Urbanek, K., Rota, M., Whang, B., Rastaldo, R., Torella, D., Tang, X.L., Rezazadeh, A., Kajstura, J., et al., 2005. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc. Natl. Acad. Sci. USA, 102(10):3766-3771.

[19] Erbs, S., Linke, A., Adams, V., Lenk, K., Thiele, H., Diederich, K.W., Emmrich, F., Kluge, R., Kendziorra, K., Sabri, O., et al., 2005. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Circ. Res., 97(8):756-762.

[20] Fazel, S., Cimini, M., Chen, L., Li, S., Angoulvant, D., Fedak, P., Verma, S., Weisel, R.D., Keating, A., Li, R.K., 2006. Cardioprotective c-kit⁺ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J. Clin. Invest., 116(7):1865-1877.

[21] Fedak, P.W., Weisel, R.D., Verma, S., Mickle, D.A., Li, R.K., 2003. Restoration and regeneration of failing myocardium with cell transplantation and tissue engineering. Semin. Thorac. Cardiovasc. Surg., 15(3):277-286.

[22] Fortuno, M.A., Ravassa, S., Fortuno, A., Zalba, G., Diez, J., 2001. Cardiomyocyte apoptotic cell death in arterial hypertension: mechanisms and potential management. Hypertension, 38(6):1406-1412.

[23] Fuchs, S., Baffour, R., Zhou, Y.F., Shou, M., Pierre, A., Tio, F.O., Weissman, N.J., Leon, M.B., Epstein, S.E., Kornowski, R., 2001. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J. Am. Coll. Cardiol., 37(6):1726-1732.

[24] Ge, J., Li, Y., Qian, J., Shi, J., Wang, Q., Niu, Y., Fan, B., Liu, X., Zhang, S., Sun, A., et al., 2006. Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart, 92(12):1764-1767.

[25] Giordano, F.J., 2003. Retrograde coronary perfusion: a superior route to deliver therapeutics to the heart? J. Am. Coll. Cardiol., 42(6):1129-1131.

[26] Gnecchi, M., He, H., Liang, O.D., Melo, L.G., Morello, F., Mu, H., Noiseux, N., Zhang, L., Pratt, R.E., Ingwall, J.S., et al., 2005. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med., 11(4):367-368.

[27] Hofmann, M., Wollert, K.C., Meyer, G.P., Menke, A., Arseniev, L., Hertenstein, B., Ganser, A., Knapp, W.H., Drexler, H., 2005. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 111(17):2198-2202.

[28] Hou, D., Youssef, E.A., Brinton, T.J., Zhang, P., Rogers, P., Price, E.T., Yeung, A.C., Johnstone, B.H., Yock, P.G., March, K.L., 2005. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation, 112(9 Suppl.):I150-I156.

[29] Hunt, S.A., 2005. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J. Am. Coll. Cardiol., 46(6):e1-e82.

[30] Hwang, W.S., Ryu, Y.J., Park, J.H., Park, E.S., Lee, E.G., Koo, J.M., Jeon, H.Y., Lee, B.C., Kang, S.K., Kim, S.J., et al., 2004. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science, 303(5664):1669-1674.

[31] 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., Goodell, M.A., 2001. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest., 107(11):1395-1402.

[32] Janssens, S., Dubois, C., Bogaert, J., Theunissen, K., Deroose, C., Desmet, W., Kalantzi, M., Herbots, L., Sinnaeve, P., Dens, J., et al., 2006. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet, 367(9505):113-121.

[33] Jiang, Y., Vaessen, B., Lenvik, T., Blackstad, M., Reyes, M., Verfaillie, C.M., 2002a. Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp. Hematol., 30(8):896-904.

[34] Jiang, Y., Jahagirdar, B.N., Reinhardt, R.L., Schwartz, R.E., Keene, C.D., Ortiz-Gonzalez, X.R., Reyes, M., Lenvik, T., Lund, T., Blackstad, M., et al., 2002b. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418(6893):41-49.

[35] Kajstura, J., Rota, M., Whang, B., Cascapera, S., Hosoda, T., Bearzi, C., Nurzynska, D., Kasahara, H., Zias, E., Bonafe, M., et al., 2005. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ. Res., 96(1):127-137.

[36] Kalka, C., Masuda, H., Takahashi, T., Kalka-Moll, W.M., Silver, M., Kearney, M., Li, T., Isner, J.M., Asahara, T., 2000. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc. Natl. Acad. Sci. USA, 97(7):3422-3427.

[37] Kamihata, H., Matsubara, H., Nishiue, T., Fujiyama, S., Tsutsumi, Y., Ozono, R., Masaki, H., Mori, Y., Iba, O., Tateishi, E., et al., 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(9):1046-1052.

[38] Kawada, H., Fujita, J., Kinjo, K., Matsuzaki, Y., Tsuma, M., Miyatake, H., Muguruma, Y., Tsuboi, K., Itabashi, Y., Ikeda, Y., et al., 2004. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood, 104(12):3581-3587.

[39] Kehat, I., Kenyagin-Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J., Gepstein, L., 2001. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J. Clin. Invest., 108(3):407-414.

[40] Kobayashi, T., Hamano, K., Li, T.S., Katoh, T., Kobayashi, S., Matsuzaki, M., Esato, K., 2000. Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model. J. Surg. Res., 89(2):189-195.

[41] Kocher, A.A., Schuster, M.D., Szabolcs, M.J., Takuma, S., Burkhoff, D., Wang, J., Homma, S., Edwards, N.M., Itescu, S., 2001. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med., 7(4):430-436.

[42] Krause, U., Harter, C., Seckinger, A., Wolf, D., Reinhard, A., Bea, F., Dengler, T., Hardt, S., Ho, A., Katus, H.A., et al., 2007. Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infarcted porcine heart. Stem Cells Dev., 16(1):31-37.

[43] Lapidot, T., Petit, I., 2002. Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp. Hematol., 30(9):973-981.

[44] Laugwitz, K.L., Moretti, A., Lam, J., Gruber, P., Chen, Y., Woodard, S., Lin, L.Z., Cai, C.L., Lu, M.M., Reth, M., et al., 2005. Postnatal isl1⁺ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 433(7026):647-753.

[45] Leobon, B., Garcin, I., Menasche, P., Vilquin, J.T., Audinat, E., Charpak, S., 2003. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc. Natl. Acad. Sci. USA, 100(13):7808-7811.

[46] Leone, A.M., Rutella, S., Bonanno, G., Abbate, A., Rebuzzi, A.G., Giovannini, S., Lombardi, M., Galiuto, L., Liuzzo, G., Andreotti, F., et al., 2005. Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function. Eur. Heart J., 26(12):1196-1204.

[47] Leri, A., Kajstura, J., Anversa, P., 2005. Cardiac stem cells and mechanisms of myocardial regeneration. Physiol. Rev., 85(4):1373-1416.

[48] Li, R.K., Jia, Z.Q., Weisel, R.D., Mickle, D.A., Zhang, J., Mohabeer, M.K., Rao, V., Ivanov, J., 1996. Cardiomyocyte transplantation improves heart function. Ann. Thorac. Surg., 62(3):654-660 (Discussion in p.660-661).

[49] Li, X., Yu, X., Lin, Q., Deng, C., Shan, Z., Yang, M., Lin, S., 2007. Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment. J. Mol. Cell. Cardiol., 42(2):295-303.

[50] Linke, A., Muller, P., Nurzynska, D., Casarsa, C., Torella, D., Nascimbene, A., Castaldo, C., Cascapera, S., Bohm, M., Quaini, F., et al., 2005. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc. Natl. Acad. Sci. USA, 102(25):8966-8971.

[51] Lunde, K., Solheim, S., Aakhus, S., Arnesen, H., Abdelnoor, M., Egeland, T., Endresen, K., Ilebekk, A., Mangschau, A., Fjeld, J.G., et al., 2006. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N. Engl. J. Med., 355(12):1199-1209.

[52] Makino, S., Fukuda, K., Miyoshi, S., Konishi, F., Kodama, H., Pan, J., Sano, M., Takahashi, T., Hori, S., Abe, H., et al., 1999. Cardiomyocytes can be generated from marrow stromal cells in vitro. J. Clin. Invest., 103(5):697-705.

[53] Mazhari, R., Hare, J.M., 2007. Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat. Clin. Pract. Cardiovasc. Med., 4(Suppl. 1):S21-S26.

[54] Menasche, P., 2003. Cell transplantation in myocardium. Ann. Thorac. Surg., 75(6 Suppl.):S20-S28.

[55] Messina, E., de Angelis, L., Frati, G., Morrone, S., Chimenti, S., Fiordaliso, F., Salio, M., Battaglia, M., Latronico, M.V., Coletta, M., et al., 2004. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res., 95(9):911-921.

[56] Metharom, P., Doyle, B., Caplice, N.M., 2007. Clinical trials in stem cell therapy: pitfalls and lessons for the future. Nat. Clin. Pract. Cardiovasc. Med., 4(Suppl. 1):S96-S99.

[57] Meyer, G.P., Wollert, K.C., Lotz, J., Steffens, J., Lippolt, P., Fichtner, S., Hecker, H., Schaefer, A., Arseniev, L., Hertenstein, B., et al., 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(10):1287-1294.

[58] Miyahara, Y., Nagaya, N., Kataoka, M., Yanagawa, B., Tanaka, K., Hao, H., Ishino, K., Ishida, H., Shimizu, T., Kangawa, K., et al., 2006. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat. Med., 12(4):459-465.

[59] Mouquet, F., Pfister, O., Jain, M., Oikonomopoulos, A., Ngoy, S., Summer, R., Fine, A., Liao, R., 2005. Restoration of cardiac progenitor cells after myocardial infarction by self-proliferation and selective homing of bone marrow-derived stem cells. Circ. Res., 97(11):1090-1092.

[60] Murad-Netto, S., Moura, R., Romeo, L.J., Manoel Neto, A., Duarte, N., Barreto, F., Jensen, A., Vina, R.F., Vraslovik, F., Oberdan, A., et al., 2004. Stem cell therapy with retrograde coronary perfusion in acute myocardial infarction. A new technique. Arq. Bras. Cardiol., 83(4):352-354, 349-351.

[61] Murry, C.E., Wiseman, R.W., Schwartz, S.M., Hauschka, S.D., 1996. Skeletal myoblast transplantation for repair of myocardial necrosis. J. Clin. Invest., 98(11):2512-2523.

[62] 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., et al., 2004. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 428(6983):664-668.

[63] Murtuza, B., Suzuki, K., Bou-Gharios, G., Beauchamp, J.R., Smolenski, R.T., Partridge, T.A., Yacoub, M.H., 2004. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc. Natl. Acad. Sci. USA, 101(12):4216-4221.

[64] Nadal-Ginard, B., Kajstura, J., Leri, A., Anversa, P., 2003. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ. Res., 92(2):139-150.

[65] Nagaya, N., Kangawa, K., Itoh, T., Iwase, T., Murakami, S., Miyahara, Y., Fujii, T., Uematsu, M., Ohgushi, H., Yamagishi, M., et al., 2005. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation, 112(8):1128-1135.

[66] Nygren, J.M., Jovinge, S., Breitbach, M., Sawen, P., Roll, W., Hescheler, J., Taneera, J., Fleischmann, B.K., Jacobsen, S.E., 2004. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat. Med., 10(5):494-501.

[67] 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., et al., 2003. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl. Acad. Sci. USA, 100(21):12313-12318.

[68] Ohnishi, S., Yanagawa, B., Tanaka, K., Miyahara, Y., Obata, H., Kataoka, M., Kodama, M., Ishibashi-Ueda, H., Kangawa, K., Kitamura, S., et al., 2007. Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. J. Mol. Cell. Cardiol., 42(1):88-97.

[69] Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., Nadal-Ginard, B., Bodine, D.M., Leri, A., Anversa, P., 2001a. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc. Natl. Acad. Sci. USA, 98(18):10344-10349.

[70] Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S.M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D.M., et al., 2001b. Bone marrow cells regenerate infarcted myocardium. Nature, 410(6829):701-705.

[71] Ott, H.C., Matthiesen, T.S., Brechtken, J., Grindle, S., Goh, S.K., Nelson, W., Taylor, D.A., 2007. The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells. Nat. Clin. Pract. Cardiovasc. Med., 4(Suppl. 1):S27-S39.

[72] Patel, A.N., Geffner, L., Vina, R.F., Saslavsky, J., Urschel, H.C.Jr, Kormos, R., Benetti, F., 2005. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J. Thorac. Cardiovasc. Surg., 130(6):1631-1638.

[73] 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., et al., 2003. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation, 107(18):2294-2302.

[74] Pfister, O., Mouquet, F., Jain, M., Summer, R., Helmes, M., Fine, A., Colucci, W.S., Liao, R., 2005. CD31⁻ but Not CD31⁺ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ. Res., 97(1):52-61.

[75] Rafii, S., Lyden, D., 2003. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med., 9(6):702-712.

[76] Rajnoch, C., Chachques, J.C., Berrebi, A., Bruneval, P., Benoit, M.O., Carpentier, A., 2001. Cellular therapy reverses myocardial dysfunction. J. Thorac. Cardiovasc. Surg., 121(5):871-878.

[77] Rangappa, S., Entwistle, J.W., Wechsler, A.S., Kresh, J.Y., 2003. Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype. J. Thorac. Cardiovasc. Surg., 126(1):124-132.

[78] Rauscher, F.M., Goldschmidt-Clermont, P.J., Davis, B.H., Wang, T., Gregg, D., Ramaswami, P., Pippen, A.M., Annex, B.H., Dong, C., Taylor, D.A., 2003. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation, 108(4):457-463.

[79] Reinecke, H., MacDonald, G.H., Hauschka, S.D., Murry, C.E., 2000. Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. J. Cell Biol., 149(3):731-740.

[80] Rosenstrauch, D., Poglajen, G., Zidar, N., Gregoric, I.D., 2005. Stem celltherapy for ischemic heart failure. Tex. Heart Inst. J., 32(3):339-347.

[81] Rosenzweig, A., 2006. Cardiac cell therapy-mixed results from mixed cells. N. Engl. J. Med., 355(12):1274-1277.

[82] Schachinger, V., Erbs, S., Elsasser, A., Haberbosch, W., Hambrecht, R., Holschermann, H., Yu, J., Corti, R., Mathey, D.G., Hamm, C.W., et al., 2006. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N. Engl. J. Med., 355(12):1210-1221.

[83] Scorsin, M., Hagege, A.A., Marotte, F., Mirochnik, N., Copin, H., Barnoux, M., Sabri, A., Samuel, J.L., Rappaport, L., Menasche, P., 1997. Does transplantation of cardiomyocytes improve function of infarcted myocardium? Circulation, 96(9 Suppl.):II188-II193.

[84] Silva, G.V., Litovsky, S., Assad, J.A., Sousa, A.L., Martin, B.J., Vela, D., Coulter, S.C., Lin, J., Ober, J., Vaughn, W.K., et al., 2005. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation, 111(2):150-156.

[85] Siminiak, T., Fiszer, D., Jerzykowska, O., Grygielska, B., Rozwadowska, N., Kalmucki, P., Kurpisz, M., 2005. Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial. Eur. Heart J., 26(12):1188-1195.

[86] Smith, R.R., Barile, L., Cho, H.C., Leppo, M.K., Hare, J.M., Messina, E., Giacomello, A., Abraham, M.R., Marban, E., 2007. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation, 115(7):896-908.

[87] Tang, Y.L., Zhao, Q., Qin, X., Shen, L., Cheng, L., Ge, J., Phillips, M.I., 2005. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann. Thorac. Surg., 80(1):229-236 (Discussion in p.236-237).

[88] Taylor, D.A., Atkins, B.Z., Hungspreugs, P., Jones, T.R., Reedy, M.C., Hutcheson, K.A., Glower, D.D., Kraus, W.E., 1998. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat. Med., 4(8):929-933.

[89] Thompson, C.A., Nasseri, B.A., Makower, J., Houser, S., McGarry, M., Lamson, T., Pomerantseva, I., Chang, J.Y., Gold, H.K., Vacanti, J.P., et al., 2003. Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation. J. Am. Coll. Cardiol., 41(11):1964-1971.

[90] Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., Jones, J.M., 1998. Embryonic stem cell lines derived from human blastocysts. Science, 282(5391):1145-1147.

[91] Tomita, S., Mickle, D.A., Weisel, R.D., Jia, Z.Q., Tumiati, L.C., Allidina, Y., Liu, P., Li, R.K., 2002. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J. Thorac. Cardiovasc. Surg., 123(6):1132-1140.

[92] Urbanek, K., Rota, M., Cascapera, S., Bearzi, C., Nascimbene, A., de Angelis, A., Hosoda, T., Chimenti, S., Baker, M., Limana, F., et al., 2005. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ. Res., 97(7):663-673.

[93] Urbanek, K., Cesselli, D., Rota, M., Nascimbene, A., de Angelis, A., Hosoda, T., Bearzi, C., Boni, A., Bolli, R., Kajstura, J., et al., 2006. Stem cell niches in the adult mouse heart. Proc. Natl. Acad. Sci. USA, 103(24):9226-9231.

[94] Wei, H.J., Chen, S.C., Chang, Y., Hwang, S.M., Lin, W.W., Lai, P.H., Chiang, H.K., Hsu, L.F., Yang, H.H., Sung, H.W., 2006. Porous acellular bovine pericardia seeded with mesenchymal stem cells as a patch to repair a myocardial defect in a syngeneic rat model. Biomaterials, 27(31):5409-5419.

[95] Wollert, K.C., Meyer, G.P., Lotz, J., Ringes-Lichtenberg, S., Lippolt, P., Breidenbach, C., Fichtner, S., Korte, T., Hornig, B., Messinger, D., et al., 2004. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet, 364(9429):141-148.

[96] Xie, X.J., Wang, J.A., Cao, J., Zhang, X., 2006. Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions. Acta Pharmacol. Sin., 27(9):1153-1158.

[97] Yamada, Y., Yokoyama, S., Wang, X.D., Fukuda, N., Takakura, N., 2007. Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow nonhematopoietic cells to differentiate into cardiomyocytes. Stem Cells, 25(5):1326-1333.

[98] Zhang, M., Methot, D., Poppa, V., Fujio, Y., Walsh, K., Murry, C.E., 2001. Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J. Mol. Cell. Cardiol., 33(5):907-921.

[99] Zimmermann, W.H., Melnychenko, I., Wasmeier, G., Didie, M., Naito, H., Nixdorff, U., Hess, A., Budinsky, L., Brune, K., Michaelis, B., et al., 2006. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat. Med., 12(4):452-458.

[100] Zohlnhöfer, D., Kastrati, A., Schomig, A., 2007. Stem cell mobilization by granulocyte-colony-stimulating factor in acute myocardial infarction: lessons from the REVIVAL-2 trial. Nat. Clin. Pract. Cardiovasc. Med., 4(Suppl. 1):S106-S109.