The heart was initially believed to be a terminally differentiated organ; once the cardiomyocytes died, no recovery could be made to replace the dead cells. However, around a decade ago, the concept of cardiac stem cells (CSCs) in adult hearts was proposed. CSCs differentiate into cardiomyocytes, keeping the heart functioning. Studies have proved the existence of stem cells in the heart. These somatic stem cells have been studied for use in cardiac regeneration. Moreover, recently, induced pluripotent stem cells (iPSCs) were invented, and methodologies have now been developed to induce stable cardiomyocyte differentiation and purification of mature cardiomyocytes. A reprogramming method has also been applied to direct reprogramming using cardiac fibroblasts into cardiomyocytes. Here, we address cardiomyocyte differentiation of CSCs and iPSCs. Furthermore, we describe the potential of CSCs in regenerative biology and regenerative medicine.
References
[1]
Braunwald, E.; Bristow, M. Congestive heart failure: Fifty years of progress. Circulation 2000, 102, IV14–IV23.
[2]
Braunwald, E.; Pfeffer, M. Ventricular enlargement and remodeling following acute myocardial infarction: Mechanisms and management. Am. J. Cardiol. 1991, 68, D1–D6, doi:10.1016/0002-9149(91)90255-J.
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. Evidence that human cardiac myocytes divide after myocardial infarction. N. Engl. J. Med. 2001, 344, 1750–1757, doi:10.1056/NEJM200106073442303.
[5]
Beltrami, A.P.; Barlucchi, L.; Torella, D.; Baker, M.; Limana, F.; Chimenti, S.; Kasahara, H.; Rota, M.; Musso, E.; Urbanek, K.; et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003, 114, 763–776, doi:10.1016/S0092-8674(03)00687-1.
[6]
Matsuura, K.; Nagai, T.; Nishigaki, N.; Oyama, T.; Nishi, J.; Wada, H.; Sano, M.; Toko, H.; Akazawa, H.; Sato, T.; et al. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J. Biol. Chem. 2004, 279, 11384–11391.
[7]
Messina, E.; De Angelis, L.; Frati, G.; Morrone, S.; Chimenti, S.; Fiordaliso, F.; Salio, M.; Battaglia, M.; Latronico, M.V.; Coletta, M.; et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res. 2004, 95, 911–921, doi:10.1161/01.RES.0000147315.71699.51.
[8]
Oh, H.; Bradfute, S.B.; Gallardo, T.D.; Nakamura, T.; Gaussin, V.; Mihina, Y.; Pocius, J.; Michael, L.H.; Behringer, R.R.; Garry, D.J.; et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl. Acad. Sci. USA 2003, 100, 12313–12318.
[9]
Linke, A.; Müller, P.; Nurzynska, D.; Casarsa, C.; Torella, D.; Nascimbene, A.; Castaldo, C.; Cascapera, S.; B？hm, M.; Quaini, F.; et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc. Natl. Acad. Sci. USA 2005, 102, 8966–8971.
[10]
Bearzi, C.; Rota, M.; Hosoda, T.; Tillmanns, J.; Nascimbene, A.; Angelis, A.D.; Yasuzawa-Amano, S.; Trofimova, I.; Siggins, R.W.; LeCaptitaine, N.; et al. Human cardiac stem cells. Proc. Natl. Acad. Sci. USA 2007, 104, 14068–14073.
[11]
Urbanek, K.; Torella, D.; Sheikh, F.; Angelis, A.D.; Nurzynska, D.; Silvesti, F.; Beltrami, C.A.; Bussani, R.; Beltrami, A.P.; Quaini, F. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc. Natl. Acad. Sci. USA 2005, 102, 8692–8697.
[12]
Martin, C.; Meeson, A.; Robertson, S.M.; Hawke, T.J.; Richardson, J.A.; Bates, S.; Goetsch, S.C.; Gallardo, T.D.; Garry, D.J. Persistent expression of the ATP-binding cassette transporter Abcg2 identifies cardiac SP cells in the developing and adult heart. Dev. Biol. 2004, 265, 262–275, doi:10.1016/j.ydbio.2003.09.028.
[13]
Pfister, O.; Oikonomopoulos, A.; Sereti, K.I.; Sohn, R.L.; Cullen, D.; Fine, G.C.; Monquet, F.; Westerman, K.; Liao, R. Role of the ATP binding cassette transporter Abcg2 in the phenotype and function of cardiac side population cells. Circ. Res. 2008, 103, 825–835, doi:10.1161/CIRCRESAHA.108.174615.
[14]
Oyama, T.; Nagai, T.; Wada, H.; Naito, A.T.; Matsuura, K.; Iwanaga, K.; Takahashi, T.; Goto, M.; Mikami, Y.; Yasuda, N.; et al. Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and In vivo. J. Cell. Biol. 2007, 176, 329–341, doi:10.1083/jcb.200603014.
Davis, D.R.; Zhang, Y.; Smith, R.R.; Cheng, K.; Terrovitis, J.; Malliaras, K.; Li, T.-S.; White, A.; Makker, R.; Marbán, E. Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue. PLoS One 2009, 4, e7195.
[17]
Davis, D.R.; Kizana, E.; Terrovitis, J.; Barth, A.S.; Zhang, Y.; Smith, R.R.; Miake, J.; Marbán, E. Isolation and expansion of functionally-competent cardiac progenitor cells directly from heart biopsies. J. Mol. Cell. Cardiol. 2010, 49, 312–321, doi:10.1016/j.yjmcc.2010.02.019.
[18]
Johnston, P.V.; Sasano, T.; Mills, K.; Evers, R.; Lee, S.-T.; Smith, R.R.; Lardo, A.C.; Lai, S.; Steenbergen, C.; Gertenblith, G.; et al. Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation 2009, 120, 1075–1083, doi:10.1161/CIRCULATIONAHA.108.816058.
[19]
Chimenti, I.; Smith, R.R.; Li, T.-S.; Gerstenblith, G.; Messina, E.; Giacomello, A.; Marbán, E. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infracted mice. Circ. Res. 2010, 106, 971–980, doi:10.1161/CIRCRESAHA.109.210682.
[20]
Cheng, K.; Li, T.-S.; Malliaras, K.; Davis, D.R.; Zhang, Y.; Marbán, E. Magnetic targeting enhances engraftment and functional benefit of iron-labeled cardiosphere-derived cells in myocardial infarction. Circ. Res. 2010, 106, 1570–1581, doi:10.1161/CIRCRESAHA.109.212589.
[21]
Malliaras, K.; Li, T.-S.; Luthringer, D.; Terrovitis, J.; Cheng, K.; Chakravarty, T.; Galang, G.; Zhang, Y.; Schoenhoff, F.; Eyk, J.V.; et al. Safety and efficacy of allogenic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells. Circulation 2012, 125, 100–112.
[22]
Lee, S.-T.; White, A.J.; Matsushita, S.; Malliaras, K.; Steenbergen, C.; Zhang, Y.; Li, T.-S.; Terrovitis, J.; Yee, K.; Simsir, S.; et al. Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction. J. Am. Coll. Cardiol. 2011, 57, 455–465.
[23]
White, A.J.; Smith, R.R.; Matsushita, S.; Chakravarty, T.; Czer, L.S.C.; Burton, K.; Schwarz, E.R.; Davis, D.R.; Wang, Q.; Reinsmoen, N.L.; et al. Intrinsic cardiac origin of human cardiosphere-derived cells. Eur. Heart J. 2011, 172, 68–75.
[24]
Lautamki, R.; Terrovitis, J.; Bonios, M.; Yu, J.; Tsui, B.M.; Abraham, M.R.; Bengel, F.M. Perfusion defect size predicts engraftment but not early retention of intra-myocardially injected cardiosphere-derived cells after acute myocardial infarction. Basic Res. Cardiol. 2011, 106, 1379–1386, doi:10.1007/s00395-011-0197-5.
[25]
Carr, C.A.; Stuckey, D.J.; Tan, J.J.; Tan, S.C.; Gomes, R.S.M.; Camelliti, P.; Messina, E.; Giacomello, A.; Ellison, G.M.; Clarke, K. Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks-an MRI study. PLoS One 2011, 6, e25669.
[26]
Makker, R.R.; Smith, R.R.; Cheng, K.; Malliaras, K.; Thomson, L.E.J.; Berman, D.; Czer, L.S.C.; Marban, L.; Mendizabal, A.; Johnston, P.V.; et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): A prospective, randomized phase 1 trial. Lancet 2012. in press.
[27]
Bolli, R.; Chugh, A.R.; D’Amario, D.; Loughran, J.H.; Stoddard, M.F.; Ikram, S.; Beache, G.M.; Wagner, S.G.; Leri, A.; Hosoda, T.; et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): Initial results of a randomized phase 1 trial. Lancet 2011, 378, 1847–1857, doi:10.1016/S0140-6736(11)61590-0.
[28]
Eisenberg, J.M.; Burns, L.; Eisenberg, C.A. Hematopoietic cells from bone marrow have the potential to differentiate into cardiomyocytes in vitro. Anat. Rec. A Discov. Mol. Cell Evol. Biol. 2003, 274, 870–882.
Abarbanell, A.M.; Coffey, A.C.; Fehrenbacher, J.W.; Beckman, D.J.; Herrmann, J.L.; Weil, B.; Meldrum, D.R. Proinflammatory cytokine effects on mesenchymal stem cell therapy for the ischemic heart. Ann. Thorac. Surg. 2009, 88, 1036–1043, doi:10.1016/j.athoracsur.2009.02.093.
[32]
Pittenger, M.F.; Martin, B.J. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res. 2004, 95, 9–20, doi:10.1161/01.RES.0000135902.99383.6f.
[33]
Uemura, R.; Xu, M.; Ahmad, N.; Ashraf, M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ. Res. 2006, 98, 1414–1421, doi:10.1161/01.RES.0000225952.61196.39.
[34]
Murry, C.; Soonpaa, M.; Reinecke, H.; Nakajima, H.; Nakajima, H.O.; Rubart, M.; Pasumarthi, K.B.; Virag, J.I.; Bartelmez, S.H.; Poppa, V.; et al. Hematopoietic stem cells do not differentiate into cardiac myocytes in myocardial infarcts. Nature 2004, 428, 664–668, doi:10.1038/nature02446.
[35]
Fazel, S.; Cimini, M.; Chen, L.; Li, S.; Angoulvant, D.; Fedak, P.; Verma, S.; Weisel, R.D.; Keating, A.; Li, R. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J. Clin. Invest. 2006, 116, 1865–1877.
[36]
Chein, K.R. Lost and found: cardiac stem cell therapy revisited. J. Clin. Invest. 2006, 116, 1838–1840, doi:10.1172/JCI29050.
[37]
Sun, J.; Li, S.; Liu, S.; Wu, J.; Weisel, R.D.; Zhuo, Y.; Yau, F.M.; Li, R.; Fazel, S.S. Improvement in cardiac function after bone marrow cell therapy is associated with increase in myocardial inflammation. Am. J. Physiol. Heart Circ. Physiol. 2009, 296, H43–H50.
[38]
Fazel, S.S.; Chen, L.; Angoulvant, D.; Li, S.; Weisel, R.D.; Keating, A.; Li, R. Activation of c-kit is necessary for mobilization of reparative bone marrow progenitor cells in response to cardiac injury. FASEB J. 2008, 22, 930–940.
[39]
Cimini, M.; Fazel, S.; Zhuo, S.; Xaymardan, M.; Fujii, H.; Weisel, R.D.; Li, R. c-Kit dysfunction impairs myocardial healing after infarction. Circulation 2007, 116, I77–I82.
[40]
Gaebel, R.; Furlani, D.; Sorg, H.; Polchow, B.; Frank, J.; Bieback, K.; Wang, W.; Klopsch, C.; Ong, L.; Li, W.; et al. Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration. PLoS One 2011, 6, e15652.
[41]
Anversa, P.; Kajstura, J.; Leri, A.; Bolli, R. Life and death of cardiac stem cells. A paradigm shift in cardiac biology. Circulation 2006, 113, 1451–1463, doi:10.1161/CIRCULATIONAHA.105.595181.
[42]
Hosoda, T.; Kajstura, J.; Leri, A.; Anversa, P. Mechanism of myocardial regeneration. Circ. J. 2010, 74, 13–17, doi:10.1253/circj.CJ-09-0665.
[43]
Tallini, Y.; Greene, K.; Craven, M.; Spealman, A.; Breitbach, M.; Smith, J.; Fisher, P.J.; Steffey, M.; Hesse, M.; Doran, R.M.; et al. c-Kit expression identifies cardiovascular precursors in the neonatal heart. Proc. Natl. Acad. Sci. USA 2009, 106, 1808–1813.
[44]
Kawaguchi, N. Stem cells for cardiac regeneration and possible roles of the transforming growth factor family. Biomol. Concept. 2012, 3, 99–106.
[45]
Miyamoto, S.; Kawaguchi, N.; Ellison, G.M.; Shin’oka, T.; Matsuoka, R.; Kurosawa, H. Characterization of long-term cultured cardiac stem cells (CSCs) derived from adult rat hearts. Stem Cells Dev. 2010, 19, 105–116, doi:10.1089/scd.2009.0041.
Wang, L.; Ma, W.; Markovich, R.; Chen, J.W.; Wang, P.H. Regulation of cardiomyocyte apoptotic signaling by insulin-like growth factor I. Circ. Res. 1998, 83, 516–252, doi:10.1161/01.RES.83.5.516.
[48]
Fujio, Y.; Nguyen, T.; Wencker, D.; Kitsis, R.N.; Walsh, K. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 2000, 101, 660–667, doi:10.1161/01.CIR.101.6.660.
[49]
Kawaguchi, N.; Smith, A.J.; Waring, C.D.; Hasan, M.K.; Miyamoto, S.; Matsuoka, R.; Ellison, G.M. c-Kit pos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling. PLoS One 2010, 5, e14297.
[50]
Kawaguchi, N. Adult cardiac-derived stem cells: Differentiation and survival regulators. In Vitamins and Hormones; Litwack, G., Ed.; Academic Press Elsevier Inc.: Oxford, UK, 2011; Volume 87, pp. 111–125.
[51]
Suslov, O.; Kukekov, V.; Ignatova, T.; Steindler, D. Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc. Natl. Acad. Sci. USA 2002, 99, 14506–11451.
[52]
Andersen, D.C.; Andersen, P.; Schneider, M.; Jensen, H.B.; Sheikh, S.P. Murine “cardiospheres” are not a source of stem cells with cardiomyogenic potential. Stem Cells 2009, 27, 1571–1581, doi:10.1002/stem.72.
[53]
Machida, M.; Takagaki, Y.; Matsuoka, R.; Kawaguchi, N. Proteomic comparison spherical aggregates and adherent cells of cardiac stem cells. Int. J. Cardiol. 2011, 153, 296–305, doi:10.1016/j.ijcard.2010.08.049.
[54]
Fathi, A.; Pakzad, M.; Taei, A.; Brink, T.C.; Pirhaji, L.; Ruiz, G.; Bordbar, M.S.T.; Gourabi, H.; Adjaye, J.; Baharvand, H.; et al. Comparative proteome and transcriptome analyses of embryonic stem cells during embryoid body-based differentiation. Proteomics 2009, 9, 4859–4870, doi:10.1002/pmic.200900003.
[55]
Wojakowski, W.; Tendera, M.; Michalowska, A.; Majka, M.; Kucia, M.; Malanskiewicz, K.; Wyderka, R.; Ochala, A.; Ratajczak, M.Z. Mobilization of CD34/CXCR4 +, CD34/CD117 +, c-met + stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelin markers into peripheral blood in patients with acute myocardial infarction. Circulation 2004, 110, 3213–3220, doi:10.1161/01.CIR.0000147609.39780.02.
Morimoto, H.; Takahashi, M.; Shiba, Y.; Izawa, A.; Ise, H.; Hongo, M.; Hatake, K.; Motoyoshi, K.; Ikeda, U. Bone marrow-derived CXCR4+ cells mobilized by macrophages colony-stimulating factor participate in the reduction of infarct area and improvement of cardiac remodeling after myocardial infarction in mice. Am. J. Pathol. 2007, 171, 755–766, doi:10.2353/ajpath.2007.061276.
Moretti, A.; Caron, L.; Nakano, A.; Lam, J.T.; Bernshausen, A.; Chen, Y.; Qyang, Y.; Bu, L.; Sasaki, M.; Martin-Puig, S.; et al. Mtipotent embryonic isl1 + progenitor cells lead to cardiac smooth muscle and endothelial cell diversification. Cell 2006, 127, 1151–1165, doi:10.1016/j.cell.2006.10.029.
[60]
Ott, H.C.; Matthiesen, T.S.; Brechtken, J.; Grindle, S.; Goh, S.K.; Nelson, W.; Tayler, D.A. The adult human as a source for stem cells: Repair strategies with embryonic-like progenitor cells. Nat. Clin. Pract. Cardiovasc. Med. 2007, 4, S27–S39, doi:10.1038/ncpcardio0771.
[61]
Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126, 663–676, doi:10.1016/j.cell.2006.07.024.
[62]
Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, 131, 861–172, doi:10.1016/j.cell.2007.11.019.
[63]
Park, I.H.; Zhao, R.; West, J.A.; Yabuuchi, A.; Huo, H.; Ince, T.A.; Lerou, P.H.; Lensch, M.W.; Daley, G.Q. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008, 451, 141–146.
[64]
Hinescu, M.E.; Popescu, L.M. Interstitial Cajal-like cells (ICLC) in human atrial myocardium. J. Cell Mol. Med. 2005, 9, 972–975, doi:10.1111/j.1582-4934.2005.tb00394.x.
[65]
Kostin, S.; Popescu, L.M. A distinct type of cell in myocardium: Interstitial Cajal-like cells (ICLC). J. Cell Mol. Med. 2009, 13, 295–308, doi:10.1111/j.1582-4934.2008.00668.x.
[66]
Gherghiceanu, M.; Manole, C.G.; Popescu, L.M. Telocytes in endocarium: Electron microscope evidence. J. Cell Mol. Med. 2010, 14, 2330–2334, doi:10.1111/j.1582-4934.2010.01133.x.
[67]
Popescu, L.M.; Manole, C.G.; Gherghiceanu, M.; Aedelean, A.; Nicolescu, M.I.; Hinescu, M.E.; Kostin, S. Telocytes in human epicardium. J. Cell Mol. Med. 2010, 14, 2085–2093, doi:10.1111/j.1582-4934.2010.01129.x.
[68]
Hasan, M.K.; Komoike, Y.; Tsunesumi, S.; Nakao, R.; Nagao, H.; Matsuoka, R.; Kawaguchi, N. Myogenic differentiation in atrium derived adult cardiac pluripotent cells and the transcriptional regulation of GATA4 and myogenin on ANP promoter. Genes Cells 2010, 15, 439–453.
Minasi, M.G.; Riminucci, M.; De Angelis, L.; Borello, U.; Berarducci, B.; Innocenzi, A.; Caprioli, A.; Sirabella, D.; Baiocchi, M.; De Maria, R.; et al. The meso-angioblast: A multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues. Development 2002, 129, 2773–2783.
[71]
Kawaguchi, N.; Nakao, R.; Yamaguchi, M.; Ogawa, D.; Matsuoka, R. TGF-β superfamily regulates a switch that mediates differentiation either into adipocytes or myocytes in left atrium derived pluripotent cells (LA-PCS). Biochem. Biophys. Res. Commun. 2010, 396, 619–625, doi:10.1016/j.bbrc.2010.04.123.
Singh, R.; Bhasin, S.; Braga, M.; Artaza, J.N.; Pervin, S.; Taylor, W.E.; Krishnan, V.; Sinha, S.K.; Rajavashisth, T.B.; Jasuja, R. Regulation of myogenic differentiation by androgens: Cross talk between androgen receptor/β-catenin and follistatin/transforming growth factor-β signaling pathways. Endocrinology 2009, 150, 1259–1268.
[75]
Sordella, R.; Jiang, W.; Chen, G.; Curto, M.; Settleman, J. Modulation of Rho GTPase signalling regulates a switch between adipogenesis and myogenesis. Cell 2003, 113, 147–158, doi:10.1016/S0092-8674(03)00271-X.
[76]
Yuasa, S.; Itabashi, Y.; Koshimizu, U.; Tanaka, T.; Sugimura, K.; Kinoshita, M.; Hattori, F.; Fukami, S.; Shimazaki, T.; Ogawa, S.; et al. Transient inhibition of BMP signaling by noggin induces cardiomyocyte differentiation of mouse embryonic stem cells. Nat. Biotechnol. 2005, 23, 607–611, doi:10.1038/nbt1093.
[77]
Kawaguchi, N.; Hayama, E.; Furutani, Y.; Nakanishi, T. Prospective in vitro models of channelopathies and cardiomyopathies. Stem Cell Int. 2012, doi:10.1155/2012/439219.
[78]
Yang, L.; Soonpaa, M.H.; Adler, E.D.; Roepke, T.K.; Kattman, S.J.; Kennedy, M.; Henckaerts, E.; Bonham, K.; Abbott, G.W.; Linden, R.M.; et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 2008, 453, 524–529.
[79]
Ren, Y.; Lee, M.Y.; Schliffke, S.; Paavola, J.; Amos, P.J.; Ge, X.; Ye, M.; Zhu, S.; Senyei, G.; Lum, L.; et al. Small molecule Wnt inhibitors enhance the efficiency of BMP-4-directed cardiac differentiation of human pluripotent stem cells. J. Mol. Cell. Cardiol. 2011, 51, 280–287, doi:10.1016/j.yjmcc.2011.04.012.
[80]
Kattman, S.J.; Witty, A.D.; Gagliardi, M.; Dubois, N.C.; Niapour, M.; Hotta, A.; Ellis, J.; Keller, G. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 2011, 8, 228–240, doi:10.1016/j.stem.2010.12.008.
[81]
Freund, C.; Mummery, C.L. Prospects for pluripotent stem cell-derived cardiomyocytes in cardiac cell therapy and as disease models. J. Cell. Biochem. 2008, 107, 592–599, doi:10.1002/jcb.22164.
[82]
Yamashita, J.K. ES and iPS cell research for cardiovascular regeneration. Exp. Cell Res. 2010, 316, 2555–2559, doi:10.1016/j.yexcr.2010.04.004.
Khalil, J.; Xi, M.; Shishechian, N.; Hannes, T.; Pfannkuche, K.; Liang, H.; Fatima, A.; Haustein, M.; Suhr, F.; Bloch, W.; et al. Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells. FASEB J. 2010, 24, 2739–2751, doi:10.1096/fj.09-145177.
[85]
Burridge, P.W.; Thompson, S.; Millrod, M.A.; Weinberg, S.; Yuan, X.; Peters, A.; Mahairaki, V.; Koliatsos, V.E.; Tung, L.; Zambidis, E.T. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability. PLoS One 2011, 6, e18293.
[86]
Cao, N.; Liu, Z.; Chen, Z.; Wang, J.; Chen, T.; Zhao, X.; Ma, Y.; Qin, L.; Kang, J.; Wei, B.; et al. Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Res. 2012, 22, 219–236, doi:10.1038/cr.2011.195.
[87]
Li, L.; Larabee, S.M.; Chen, S.; Basiri, L.; Yamaguchi, S.; Zakaria, A.; Gallicano, G.I. Novel 5′TOP mRNAs regulated by ribosomal S6 kinase are important for cardiomyocyte development: S6 kinase suppression limits cardiac differentiation and promotes pluripotent cells toward a neural lineage. Stem Cells Dev. 2011, 1, 1538–1548.
[88]
Kempf, H.; Lecina, M.; Ting, S.; Zweigerdt, R.; Oh, S. Distinct regulation of mitogen-activated protein kinase activities is coupled with enhanced cardiac differentiation of human embryonic stem cells. Stem Cell Res. 2011, 7, 198–209, doi:10.1016/j.scr.2011.06.001.
[89]
Sachinidis, A.; Schwengberg, S.; Hippler-Altenburg, R.; Mariappan, D.; Kamisetti, N.; Seelig, B.; Berkessel, A.; Hescheler, J. Identification of small signaling molecules promoting cardiac-specific differentiation of mouse embryonic stem cells. Cell. Physiol. Biochem. 2006, 18, 303–314, doi:10.1159/000097608.
[90]
Hao, J.; Daleo, M.A.; Murphy, C.K.; Yu, P.B.; Ho, J.N.; Hu, J.; Peterson, R.T.; Hatzopoulos, A.K.; Hong, C.C. Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cell. PLoS One 2008, 3, e2094.
[91]
Wang, H.J.; Hao, J.; Hong, C.C. Cardiac induction of embryonic stem cells by a small molecule inhibitor of Wnt/β-catenin signaling. ACS Chem. Biol. 2011, 6, 92–197.
Egashira, T.; Yuasa, S.; Fukuda, K. Induced pluripotent stem cells in cardiovascular medicine. Stem Cells Int. 2011, doi:10.4061/2011/348960.
[94]
Dubois, N.C.; Craft, A.M.; Sharma, P.; Elliott, D.A.; Stanley, E.G.; Elefanty, A.G.; Gramolini, A.; Keller, G. SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat. Biotechnol. 2011, 29, 1011–1018.
[95]
Ieda, M.; Fu, J.; Delgado-Olguin, P.; Vadantham, V.; Hayashi, Y.; Bruneau, B.G.; Srivastava, D. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 2010, 142, 375–386, doi:10.1016/j.cell.2010.07.002.
[96]
Qian, L.; Huang, Y.; Spencer, C.J.; Foley, A.; Vedantham, V.; Liu, L.; Conway, S.J.; Fu, J.-D.; Srivastava, D. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 2012, 485, 593–598, doi:10.1038/nature11044.
Moskowitz, I.P.G.; Kim, J.B.; Moore, M.L.; Wolf, C.M.; Peterson, M.A.; Shendure, J.; Nobrega, M.A.; Yokota, Y.; Berul, C.; Izumo, S.; et al. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell 2007, 129, 1365–1376, doi:10.1016/j.cell.2007.04.036.
[99]
Gimble, J.; Katz, A.; Bunnell, B. Adipose-derived stem cells for regenerative medicine. Circ. Res. 2007, 100, 1249–1260, doi:10.1161/01.RES.0000265074.83288.09.
[100]
Madonna, R.; Geng, Y.; De Caterina, R. Adipose tissue-derived stem cells: characterization and potential for cardiovascular repair. Arterioscler Thromb. Vasc. Biol. 2009, 29, 1723–1729, doi:10.1161/ATVBAHA.109.187179.
[101]
Hosseinkhani, H.; Hosseinkhani, M.; Hattori, S.; Matsuoka, R.; Kawaguchi, N. Micro and nano-scale in vitro 3D culture system for cardiac stem cells. J. Biomed. Mater. Res. Part A 2010, 94, 1–8.
[102]
Sekine, H.; Shimizu, T.; Dobashi, I.; Matsuura, K.; Hagiwara, H.; Takahashi, M.; kobayashi, E.; Yamato, M.; Okano, T. Cardiac cell sheet transplantation improves damaged heart function via superior cell survival in comparison with dissociated cell injection. Tissue Eng. Part A 2011, 17, 2973–2980, doi:10.1089/ten.tea.2010.0659.
