Research abstract
Article abstract
Nature Biotechnology 25, 1015 - 1024 (2007)
Published online: 26 August 2007 | doi:10.1038/nbt1327
Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts
Michael A Laflamme1,2,6, Kent Y Chen1,2,3,6, Anna V Naumova1,4, Veronica Muskheli1,2, James A Fugate1,2, Sarah K Dupras1,2, Hans Reinecke1,2, Chunhui Xu5, Mohammad Hassanipour5, Shailaja Police5, Chris O'Sullivan5, Lila Collins5, Yinhong Chen5, Elina Minami1,3, Edward A Gill3, Shuichi Ueno1,2, Chun Yuan1,4, Joseph Gold5 & Charles E Murry1,2
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.
- Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, 815 Mercer Street, Seattle, Washington 98109, USA.
- Department of Pathology, University of Washington, 815 Mercer Street, Seattle, Washington 98109, USA.
- Department of Medicine/Cardiology, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
- Vascular Imaging Laboratory, Department of Radiology, University of Washington, 815 Mercer Street, Seattle, Washington 98109, USA.
- Geron Corporation, 230 Constitution Drive, Menlo Park, California 94025, USA.
- These authors contributed equally to this work.
Correspondence to: Charles E Murry1,2 e-mail: murry@u.washington.edu
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