Abstract
Current treatments for ischemic heart disease (IHD) are generally limited to palliative measures and do not halt or reverse the loss of cardiac muscle cells, the defining characteristic of the disease. Recent findings in the stem cell and developmental biology fields have suggested the possibility of generating new heart muscle using cells derived from a variety of sources. These include adult autologous stem cells found in bone marrow or skeletal muscle, autologous cardiac progenitor cells, embryonic stem cells, and induced pluripotent stem cells or other types of reprogrammed cells. Beating cardiomyocytes have been successfully obtained from a number of these different cell types in both murine and human models, but significant technical challenges remain before cell-based cardiac regeneration is a viable therapy. Nevertheless, a large research effort is underway to address these challenges, and the outlook for revolutionizing the treatment of IHD is optimistic.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
National Center for Health Statistics. (2009) Health, United States, 2008, with Chartbook. National Center for Health Statistics. Hyattsville, MD.
Mackay, J. and Mensah, G. (2004) The Atlas of Heart Disease and Stroke. World Health Organization. Geneva, Switzerland.
Ahuja, P., Sdek, P., and MacLellan W.R. (2007) Cardiac myocyte cell cycle control in development, disease, and regeneration. Physiol. Rev. 87, 521-544.
Rubart, M. and Field, L.J. (2006) Cardiac regeneration: repopulating the heart. Annu. Rev. Physiol. 68, 29-49.
Okabe, M., Tsukahara, Y., Tanaka, M., et al. (2009) Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver. Development 136, 1951-1960.
Sherwood, R.I., Christensen, J.L., Conboy, I.M., et al. (2004) Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119, 543-554.
Li, A., Pouliot, N., Redvers, R., et al. (2004) Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny. J. Clin. Invest. 113, 390-400.
Baum, C.M., Weissman, I.L., Tsukamoto, A.S., et al. (1992) Isolation of a candidate human hematopoietic stem-cell population. Proc. Natl. Acad. Sci. U. S. A. 89, 2804-2808.
Beltrami, A.P., Barlucchi, L., Torella, D., et al. (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114, 763-776.
Laugwitz, K.L., Moretti, A., Lam, J., et al. (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433, 647-653.
Martin, C.M., Meeson, A.P., Robertson, S.M., et al. (2004) Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev. Biol. 265, 262-275.
Oh, H., Bradfute, S.B., Gallardo, T.D., et al. (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl. Acad. Sci. U. S. A. 100, 12313-12318.
Segers, V. and Lee, R.T. (2008) Stem-cell therapy for cardiac disease. Nature 451, 937-942.
Yoon, P.D., Kao, R.L., and Magovern, G.J. (1995) Myocardial regeneration. Transplanting satellite cells into damaged myocardium. Tex. Heart Inst. J. 22, 119-125.
Taylor, D.A., Atkins, B.Z., Hungspreugs, P., et al. (1998) Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat. Med. 4, 929-933.
Iijima, Y., Nagai, T., Mizukami, M., et al. (2003) Beating is necessary for transdifferentiation of skeletal muscle-derived cells into cardiomyocytes. FASEB J. 17, 1361-1363.
Winitsky, S.O., Gopal, T.V., Hassanzadeh, S., et al. (2005) Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro. PLOS Biol. 3, e87.
Gavira, J.J., Perez-Ilzarbe, M., Abizanda, G., et al. (2006) A comparison between percutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction. Cardiovasc. Res. 71, 744-753.
Gavira, J.J., Herreros, J., Perez, A., et al. (2006) Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up. J. Thorac. Cardiovasc. Surg. 131, 799-804.
Menasche, P., Hagege, A.A., Scorsin, M., et al. (2001) Myoblast transplantation for heart failure. Lancet 357, 279-280.
Perez-Ilzarbe, M., Agbulut, O., Pelacho, B., et al. (2008) Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium. Eur. J. Heart Fail. 10, 1065-1072.
Laflamme, M.A. and Murry, C.E. (2005) Regenerating the heart. Nat. Biotechnol. 23, 845-856.
Leobon, B., Garcin, I., Menasche, P., et al. (2003) Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc. Natl. Acad. Sci. U. S. A. 100, 7808-7811.
Menasche, P., Hagege, A.A., Vilquin, J.T., et al. (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J. Am. Coll. Cardiol. 41, 1078-1083.
Hocht-Zeisberg, E., Kahnert, H., Guan, K., et al. (2004) Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation. Eur. Heart J. 25, 749−758.
Glaser, R., Lu, M.M., Narula, N., Epstein, J.A. (2002) Smooth muscle cells, but not myocytes, of host origin in transplanted human hearts. Circulation 106, 17−19.
Deb, A., Wang, S., Skelding, K.A., et al. (2003) Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation 107, 1247−1249.
Bittner, R.E., Schofer, C., Weipoltshammer, K., et al. (1999) Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat. Embryol. (Berl) 199, 391−396.
Erbs, S., Linke, A., Schachinger, V., et al. (2007) Restoration of microvascular function in the infarct-related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial. Circulation 116, 366-374.
Wollert, K.C., Meyer, G.P., Lotz, J., et al. (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364, 141−148.
Laflamme, M.A., Myerson, D., Saffitz, J.E., et al. (2002) Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circ. Res. 90, 634−640.
Zhou, Q. and Melton, D.A. (2008) Extreme makeover: converting one cell into another. Cell Stem Cell 3, 382-388.
Amit, M., Carpenter, M.K., Inokuma, M.S., et al. (2000) Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev. Biol. 227, 271−278.
Doetschman, T.C., Eistetter, H., Katz, M., et al. (1985) The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morphol. 87, 27−45.
Xu, C., Police, S., Rao, N., Carpenter, M.K. (2002) Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ. Res. 91, 501−508.
Fijnvandraat, A.C., van Ginneken, A.C., de Boer, P.A., et al. (2003) Cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube. Cardiovasc. Res. 58, 399−409.
Nussbaum, J., Minami, E., Laflamme, M.A., et al. (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J. 21, 1345-1357.
Hodgson, D.M., Behfar, A., Zingman, L.V. et al. (2004) Stable benefit of embryonic stem cell therapy in myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 287, H471−H479.
Klug, M.G., Soonpaa, M.H., Koh, G.Y., et al. (1996) Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J. Clin. Invest. 98, 216−224.
Wobus, A.M., Kaomei, G., Shan, J. et al. (1997) Retinoic acid accelerates embryonic stem cell-derived cardiac differentiation and enhances development of ventricular cardiomyocytes. J. Mol. Cell Cardiol. 29, 1525−1539.
Takahashi, T., Lord, B., Schulze, P.C., et al. (2003) Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Circulation 107, 1912−1916.
Kawai, T., Takahashi, T., Esaki, M., et al. (2004) Efficient cardiomyogenic differentiation of embryonic stem cell by fibroblast growth factor 2 and bone morphogenetic protein 2. Circ. J. 68, 691−702.
Terami, H., Hidaka, K., Katsumata, T., et al. (2004) Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes. Biochem. Biophys. Res. Commun. 325, 968−975.
Semb, H. (2006) Human embryonic stem cells: origin, properties and applications. APMIS 113, 743-750.
Zou, K., Yuan, Z., Yang, Z., et al. (2009) Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat. Cell Biol. 11, 631-636.
Snir, M., Kehat, I., Gepstein, A., et al. (2003) Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 285, H2355−H2363.
Laflamme, M.A., Gold, J., Xu, C., et al. (2005) Formation of human myocardium in the rat heart from human embryonic stem cells. Am. J. Pathol. 167, 663-671.
Laflamme, M.A., Chen, K.Y., Naumova, A.V., et al. (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat. Biotechnol. 25, 1015-1024.
van Laake, L.W., Passier, R., Doevendans, P.A., et al. (2008) Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ. Res. 102, 1008-1010.
Takahashi, K. and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 652-655.
Mauritz, C., Schwanke, K., Reppel, M., et al. (2008) Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation 118, 507-517.
Zhang, J., Wilson, G.F., Soerens, A.G., et al. (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ. Res. 104, e30-e41.
Yamanaka, S. (2009) A fresh look at iPS cells. Cell 137, 13-17.
Zhao, R. and Daley, G.Q. (2008) From fibroblasts to iPS cells: induced pluripotency by defined factors. J. Cell. Biochem. 105, 949-955.
Stadtfeld, M., Nagaya, M., Utikal, J., et al. (2008) Induced pluripotent stem cells generated without viral integration. Science 322, 945-949.
Kaji, K., Norrby, K., Paca, A., et al. (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458, 771-775.
Shi, Y., Desponts, C., Do, J.T., et al. (2008) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3, 568-574.
Brockes, J.P. and Kumar, A. (2002) Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nat. Rev. Mol. Cell Biol. 3, 566-574.
Davis, R.L., Weintraub, H., and Lassar, A.B. (1987) Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987-1000.
Xie, H., Ye, M., Feng, R., et al. (2004) Stepwise reprogramming of B cells into macrophages. Cell 117, 663-676.
Zhou, Q., Brown, J., Kanarek, A., et al. (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455, 627-632.
Martin-Puig, S., Wang, Z., and Chien, K.R. (2008) Lives of a heart cell: tracing the origins of cardiac progenitors. Cell Stem Cell 2, 320-331.
Takeuchi, J.K. and Bruneau, BG. (2009) Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459, 708-711.
Bergmann, O., Bhardwaj, R.D., Bernard, S., et al. (2009) Evidence for cardiomyocyte renewal in humans. Science 324, 98-102.
Hsieh, P.C., Segers, V.F., Davis, M.E., et al. (2007) Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat. Med. 13, 970-974.
Baker, D.E., Harrison, N.J., Maltby, E., et al. (2007) Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat. Biotechnol. 25, 207-215.
Kuhn, B., del Monte, F., Hajjar, R.J., et al. (2007) Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat. Med. 13, 962-969.
Tateishi, K., Takehara, N., Matsubara, H., et al. (2008) Stemming heart failure with cardiac- or reprogrammed-stem cells. J. Cell. Mol. Med. 12, 2217-2232.
Laugwitz, K.L., Moretti, A., Lam, J., et al. (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433, 647−653.
Oh, H., Bradfute, S.B., Gallardo, T.D., et al. (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl. Acad. Sci. U. S. A. 100, 12313−12318.
Dawn, B., Stein, A.B., Urbanek, K., et al. (2005) Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc. Natl. Acad. Sci. U. S. A. 102, 3766-3771.
Wu, S.M., Chien, K.R., Mummery, C. (2008) Origins and fates of cardiovascular progenitor cells. Cell. 132, 537–543.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Huang, X., Oh, J., Wu, S.M. (2011). Regenerative Strategies for Cardiac Disease. In: Appasani, K., Appasani, R. (eds) Stem Cells & Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-860-7_35
Download citation
DOI: https://doi.org/10.1007/978-1-60761-860-7_35
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-859-1
Online ISBN: 978-1-60761-860-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)