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Epicardial Cells Derived from Human Embryonic Stem Cells Augment Cardiomyocyte-Driven Heart Regeneration

By August 16, 2019No Comments

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This week we profile a recent publication in Nature Biotechnology from
the laboratory of Dr. Charles Murry (pictured) at the UW School of Medicine.

 Can you provide a brief overview of your lab’s current research focus?

My lab works in stem cell biology with a focus on the cardiovascular system. Our basic science efforts focus on the mechanism of cardiovascular cell differentiation, and we’re currently obsessed with events in the nucleus (e.g. dynamics of chromosomal architecture). We do disease-in-a-dish studies, using human iPSCs from patients with genetically-based heart muscle diseases to generate cardiac muscle afflicted with cardiomyopathies. Our long term goal is to harness the power of stem cells to regenerate the human heart, creating a one-and-done therapy to prevent or reverse heart failure.

What is the significance of the findings in this publication?

We previously showed that transplanting human heart muscle cells into myocardial infarcts resulted in partial heart regeneration and enhanced cardiac function. It has been difficult to completely remuscularize the heart, because so many cells die shortly after transplantation. In the current study, we embraced complexity and added a second cell population, the epicardial cell, that normally lines the surface of the heart. Epicardial cells produce growth factors for cardiac muscle cells, and they also give rise to the heart’s connective tissue and blood vessels. We found that the epicardial cells helped build better heart muscle, generating grafts with 3-fold more heart muscle, 2.5-fold greater cell division, better blood vessels and a better connective tissue.  The combination of these factors significantly enhanced cardiac function, compared to delivery of cardiomyocyte monocultures.

What are the next steps for this research?

We are interested in testing whether adding epicardial cells will enhance the maturity of cardiomyocytes to the point where they eliminate the phase of electrical instability (arrhythmias) that last for several weeks after transplantation. If so, this may be a great approach to heart regeneration in human patients.

This work was funded by:

This work was supported by the National Institutes of Health (thank you US taxpayers) and the Fondation Leducq.

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