Expandable Cardiovascular Progenitor Cells Reprogrammed from Fibroblasts

• Fibroblasts can be reprogrammed into cardiac progenitor cells (CPCs)
• CPCs expanded long term under defined conditions generate cardiovascular cells
• Transplanting expanded CPCs improves heart function after myocardial infarction
• CPCs can be captured during PSC differentiation and expanded in the same conditions

SummaryStem 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 105 starting fibroblasts robustly producing 1016 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.

Graphical AbstractFigure optionsDownload high-quality image (255 K)Download as PowerPoint slide