Stem Cell Therapy Repairs Damaged Heart Muscle in Mouse Myocardial Infarction Model

Advanced stem cell techniques were used to generate expandable cardiovascular progenitor cells (ieCPCs) from skin fibroblasts, which could repair damage to the heart muscle caused by myocardial infarction.

Use of stem cells to repair damaged heart muscle has been only partially successful due to failure of the cells to self-renew or failure to generate all three types of cells—cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs)—that the heart requires to heal and function properly.

In the current study, investigators at the University of California, San Francisco's Gladstone Institutes (USA) worked with a mouse heart disease model. They 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.

The investigators reported in the March 3, 2016, online edition of the journal Cell Stem Cell that the 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.

"Cardiac progenitor cells could be ideal for heart regeneration," said senior author Dr. Sheng Ding, professor of pharmaceutical chemistry at the Gladstone Institutes. "They are the closest precursor to functional heart cells, and, in a single step, they can rapidly and efficiently become heart cells, both in a dish and in a live heart. With our new technology, we can quickly create billions of these cells in a dish and then transplant them into damaged hearts to treat heart failure."

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Gladstone Institutes