Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug discovery and disease modeling: From the genetic, epigenetic, and tissue modeling perspectives

被引:0
作者
Chow M.Z. [1 ,2 ]
Boheler K.R. [1 ,2 ,3 ]
Li R.A. [1 ,2 ,4 ]
机构
[1] Stem Cell and Regenerative Medicine Consortium, Faculty of Medicine, University of Hong Kong, Hong Kong
[2] Department of Physiology, University of Hong Kong, Faculty of Medicine Building, Pokfulam
[3] Molecular Cardiology and Stem Cell Unit, National Institute on Aging, Gerontology Research Center, Baltimore, MD 21224
[4] Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574
关键词
Cardiac differentiation; Cardiomyocyte; Chromatin remodeling; Epigenetic regulations; Histone modification; Human embryonic stem cell; Induced pluripotent stem cell; Regenerative medicine;
D O I
10.1186/scrt308
中图分类号
学科分类号
摘要
Heart diseases remain a major cause of mortality and morbidity worldwide. However, terminally differentiated human adult cardiomyocytes (CMs) possess a very limited innate ability to regenerate. Directed differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into CMs has enabled clinicians and researchers to pursue the novel therapeutic paradigm of cell-based cardiac regeneration. In addition to tissue engineering and transplantation studies, the need for functional CMs has also prompted researchers to explore molecular pathways and develop strategies to improve the quality, purity and quantity of hESC-derived and iPSC-derived CMs. In this review, we describe various approaches in directed CM differentiation and driven maturation, and discuss potential limitations associated with hESCs and iPSCs, with an emphasis on the role of epigenetic regulation and chromatin remodeling, in the context of the potential and challenges of using hESC-CMs and iPSC-CMs for drug discovery and toxicity screening, disease modeling, and clinical applications. © 2013 BioMed Central Ltd.
引用
收藏
相关论文
共 120 条
[61]  
Ieda M., Fu J.D., Delgado-Olguin P., Vedantham V., Hayashi Y., Bruneau B.G., Srivastava D., Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors, Cell, 142, pp. 375-386, (2010)
[62]  
Qian L., Huang Y., Spencer C.I., 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, 485, pp. 593-598, (2012)
[63]  
Takeuchi J.K., Bruneau B.G., Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors, Nature, 459, pp. 708-711, (2009)
[64]  
Chen J.X., Krane M., Deutsch M.A., Wang L., Rav-Acha M., Gregoire S., Engels M.C., Rajarajan K., Karra R., Abel E.D., Wu J.C., Milan D., Wu S.M., Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5, Circ Res, 111, pp. 50-55, (2012)
[65]  
Kawamura T., Ono K., Morimoto T., Wada H., Hirai M., Hidaka K., Morisaki T., Heike T., Nakahata T., Kita T., Hasegawa K., Acetylation of GATA-4 is involved in the differentiation of embryonic stem cells into cardiac myocytes, Journal of Biological Chemistry, 280, 20, pp. 19682-19688, (2005)
[66]  
Vallaster M., Vallaster C.D., Wu S.M., Epigenetic mechanisms in cardiac development and disease, Acta Biochim Biophys Sin, 44, pp. 92-102, (2012)
[67]  
Van Weerd J.H., Koshiba-Takeuchi K., Kwon C., Takeuchi J.K., Epigenetic factors and cardiac development, Cardiovasc Res, 91, pp. 203-211, (2011)
[68]  
Lim L.P., Lau N.C., Garrett-Engele P., Grimson A., Schelter J.M., Castle J., Bartel D.P., Linsley P.S., Johnson J.M., Microarray analysis shows that some microRNAs downregulate large numbers of-target mRNAs, Nature, 433, 7027, pp. 769-773, (2005)
[69]  
Wang Y., Medvid R., Melton C., Jaenisch R., Blelloch R., DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal, Nature Genetics, 39, 3, pp. 380-385, (2007)
[70]  
Bernstein E., Kim S.Y., Carmell M.A., Murchison E.P., Alcorn H., Li M.Z., Mills A.A., Elledge S.J., Anderson K.V., Hannon G.J., Dicer is essential for mouse development, Nature Genetics, 35, 3, pp. 215-217, (2003)