Journal Article10.1038/NBT1327
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.
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Abstract: Cardiomyocytes derived from human embryonic stem (hES) cells potentially offer large numbers of cells to facilitate repair of the infarcted heart. However, this approach has been limited by inefficient differentiation of hES cells into cardiomyocytes, insufficient purity of cardiomyocyte preparations and poor survival of hES cell-derived myocytes after transplantation. Seeking to overcome these challenges, we generated highly purified human cardiomyocytes using a readily scalable system for directed differentiation that relies on activin A and BMP4. We then identified a cocktail of pro-survival factors that limits cardiomyocyte death after transplantation. These techniques enabled consistent formation of myocardial grafts in the infarcted rat heart. The engrafted human myocardium attenuated ventricular dilation and preserved regional and global contractile function after myocardial infarction compared with controls receiving noncardiac hES cell derivatives or vehicle. The ability of hES cell-derived cardiomyocytes to partially remuscularize myocardial infarcts and attenuate heart failure encourages their study under conditions that closely match human disease.
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Citations
Directed and Systematic Differentiation of Cardiovascular Cells From Mouse Induced Pluripotent Stem Cells
Genta Narazaki,Hideki Uosaki,Mizue Teranishi,Keisuke Okita,Bongju Kim,Satoshi Matsuoka,Shinya Yamanaka,Jun K. Yamashita +7 more
TL;DR: The differentiation properties of iPS cells are almost completely identical to those of ES cells, which would greatly contribute to a novel understanding of i PS cell biology and the development of novel cardiovascular regenerative medicine.
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Reprogramming of human fibroblasts toward a cardiac fate
Young-Jae Nam,Kunhua Song,Xiang Luo,Edward Daniel,Kaleb Lambeth,Katherine West,Joseph A. Hill,J. Michael DiMaio,Linda A. Baker,Rhonda Bassel-Duby,Eric N. Olson +10 more
TL;DR: Findings indicate that human fibroblasts can be reprogrammed to cardiac-like myocytes by forced expression of cardiac transcription factors with muscle-specific microRNAs and represent a step toward possible therapeutic application of this reprogramming approach.
524
Moving from static to dynamic complexity in hydrogel design
TL;DR: Progress in polymer synthesis and processing has led to a new generation of dynamic systems that are capable of responding to artificial triggers and biological signals with spatial precision, which will open up new possibilities for the use of hydrogels as model biological structures and in tissue regeneration.
Control of human embryonic stem cell colony and aggregate size heterogeneity influences differentiation trajectories.
Celine Bauwens,Raheem Peerani,Sylvia Niebruegge,Kimberly A. Woodhouse,Eugenia Kumacheva,Mansoor Husain,Peter W. Zandstra +6 more
TL;DR: It is demonstrated that heterogeneity in hESC colony and aggregate size produces subsets of appropriate conditions for differentiation into specific cell types, and suggested that the local microenvironment modulates endogenous parameters that can be used to influence pluripotent cell differentiation trajectories.
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Synthetic peptide-acrylate surfaces for long-term self-renewal and cardiomyocyte differentiation of human embryonic stem cells
Zara Melkoumian,Jennifer L. Weber,David M. Weber,Andrei Gennadyevich Fadeev,Yue Zhou,Paula Dolley-Sonneville,Jiwei Yang,Liqun Qiu,Catherine A. Priest,Christopher B. Shogbon,Arthur W. Martin,Jodelle Karen Nelson,Peter West,James P. Beltzer,Santona Pal,Ralph Brandenberger +15 more
TL;DR: Synthetic peptide-acrylate surfaces (PAS) are described that support self-renewal of hESCs in chemically defined, xeno-free medium and cell morphology and phenotypic marker expression were similar for cells cultured on PAS or Matrigel.
492
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TL;DR: A successful feeder-free hES culture system in which undifferentiated cells can be maintained for at least 130 population doublings and are suitable for scaleup production is demonstrated.
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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
TL;DR: 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.
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