Journal
CELL STEM CELL
Volume 18, Issue 3, Pages 368-381Publisher
CELL PRESS
DOI: 10.1016/j.stem.2016.02.001
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Funding
- California Institute for Regenerative Medicine (CIRM)
- American Heart Association (AHA) [13SDG14580035]
- National Institute of Child Health and Human Development
- National Heart, Lung, and Blood Institute (NHLBI) [U01HL098179, U01 HL100406, R01HL114948]
- National Institutes of Health (NIH)
- Roddenberry Foundation (RF)
- William K. Bowes, Jr. Foundation
- NIH
- Younger Family Foundation
- Whittier Foundation
- CIRM
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Stem cell-based approaches to cardiac regeneration are increasingly viable strategies for treating heart failure. Generating abundant and functional autologous cells for transplantation in such a setting, however, remains a significant challenge. Here, we isolated a cell population with extensive proliferation capacity and restricted cardiovascular differentiation potentials during cardiac transdifferentiation of mouse fibroblasts. These induced expandable cardiovascular progenitor cells (ieCPCs) proliferated extensively for more than 18 passages in chemically defined conditions, with 10(5) starting fibroblasts robustly producing 10(16) ieCPCs. ieCPCs expressed cardiac signature genes and readily differentiated into functional cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) in vitro, even after long-term expansion. When transplanted into mouse hearts following myocardial infarction, ieCPCs spontaneously differentiated into CMs, ECs, and SMCs and improved cardiac function for up to 12 weeks after transplantation. Thus, ieCPCs are a powerful system to study cardiovascular specification and provide strategies for regenerative medicine in the heart.
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