Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes.
Izhak Kehat,Dorit Kenyagin-Karsenti,Mirit Snir,Hana Segev,Michal Amit,Amira Gepstein,Erella Livne,Ofer Binah,Joseph Itskovitz-Eldor,Lior Gepstein +9 more
TLDR
The human ES cell--derived cardiomyocytes displayed structural and functional properties of early-stage cardiomers, which may have significant impact on the study of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering.Abstract:
The study of human cardiac tissue development is hampered by the lack of a suitable in vitro model. We describe the phenotypic properties of cardiomyocytes derived from human embryonic stem (ES) cells. Human ES cells were cultivated in suspension and plated to form aggregates termed embryoid bodies (EBs). Spontaneously contracting areas appeared in 8.1% of the EBs. Cells from the spontaneously contracting areas within EBs were stained positively with anti-cardiac myosin heavy chain, anti--alpha-actinin, anti-desmin, anti--cardiac troponin I (anti-cTnI), and anti-ANP antibodies. Electron microscopy revealed varying degrees of myofibrillar organization, consistent with early-stage cardiomyocytes. RT-PCR studies demonstrated the expression of several cardiac-specific genes and transcription factors. Extracellular electrograms were characterized by a sharp component lasting 30 +/- 25 milliseconds, followed by a slow component of 347 +/- 120 milliseconds. Intracellular Ca(2+) transients displayed a sharp rise lasting 130 +/- 27 milliseconds and a relaxation component lasting 200--300 milliseconds. Positive and negative chronotropic effects were induced by application of isoproterenol and carbamylcholine, respectively. In conclusion, the human ES cell--derived cardiomyocytes displayed structural and functional properties of early-stage cardiomyocytes. Establishment of this unique differentiation system may have significant impact on the study of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering.read more
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Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts
Michael A. Laflamme,Kent Chen,Anna V. Naumova,Veronica Muskheli,James A. Fugate,Sarah K. Dupras,Hans Reinecke,Chunhui Xu,Mohammad Hassanipour,Chris O'Sullivan,Lila R. Collins,Yinhong Chen,Elina Minami,Edward A. Gill,Shuichi Ueno,Chun Yuan,Joseph K. Gold,Charles E. Murry +17 more
TL;DR: This work generated highly purified human cardiomyocytes using a readily scalable system for directed differentiation that relies on activin A and BMP4, and identified a cocktail of pro-survival factors that limitsCardiomyocyte death after transplantation.
Journal ArticleDOI
Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions
Xiaojun Lian,Jianhua Zhang,Samira M. Azarin,Kexian Zhu,Laurie B. Hazeltine,Xiaoping Bao,Cheston Hsiao,Timothy J. Kamp,Sean P. Palecek +8 more
TL;DR: Functional human cardiomyocytes differentiated via these protocols may constitute a potential cell source for heart disease modeling, drug screening and cell-based therapeutic applications.
Journal ArticleDOI
Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells
Jianhua Zhang,Gisela F. Wilson,Andrew G. Soerens,Chad H. Koonce,Junying Yu,Sean P. Palecek,James A. Thomson,Timothy J. Kamp +7 more
TL;DR: It is concluded that human iPS cells are a viable option as an autologous cell source for cardiac repair and a powerful tool for cardiovascular research.
PatentDOI
Differentiation of human embryonic stem cells to cardiomyocytes
TL;DR: This is the first demonstration of induction ofcardiomyocyte differentiation in hES cells that do not undergo spontaneous cardiogenesis and provides a model for the study of human cardiomyocytes in culture and could be a step forward in the development of cardiomeocyte transplantation therapies.
Journal ArticleDOI
Embryonic stem cell differentiation: emergence of a new era in biology and medicine
TL;DR: Recent advances in understanding of ES cell differentiation have provided new insights essential for establishing ES cell-based developmental models and for the generation of clinically relevant populations for cell therapy.
References
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James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
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TL;DR: The derivation of pluripotent embryonic stem (ES) cells from human blastocysts is described, providing a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.
Journal ArticleDOI
Clonally Derived Human Embryonic Stem Cell Lines Maintain Pluripotency and Proliferative Potential for Prolonged Periods of Culture
Michal Amit,Melissa K. Carpenter,Margaret S. Inokuma,Choy-Pik Chiu,Charles P. Harris,Michelle A. Waknitz,Joseph Itskovitz-Eldor,James A. Thomson +7 more
TL;DR: The clonal derivation of two human ES cell lines, H9.1 and H.2, demonstrates the pluripotency of single human ES cells, the maintenance of pluripOTency during an extended period of culture, and the long-term self-renewing properties of cultured human ES Cells.
Journal ArticleDOI
Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers.
Joseph Itskovitz-Eldor,Maya Schuldiner,Dorit Karsenti,Amir Eden,Ofra Yanuka,Michal Amit,Hermona Soreq,Nissim Benvenisty +7 more
TL;DR: The ability to induce formation of human embryoid bodies that contain cells of neuronal, hematopoietic and cardiac origins will be useful in studying early human embryonic development as well as in transplantation medicine.