ETI

Pilot Project

Chenleng Cai
Chenleng Cai, PhD
Assistant Professor Developmental and Regenerative Biology
Mount Sinai School of Medicine

The Multipotency of Epicardial Cells and Mammalian Cardiac Repair and Regeneration

Cardiovascular disease (CVD) is the leading cause of death in the world. While a wide array of medical and surgical therapies have been developed, few are curative. Stem cell therapy that replaces diseased, dysfunctional cells with healthy, functioning ones could potentially provide more effective treatment for many forms of CVD. To facilitate this, it is important to identify the optimal source of stem cells for achieving cardiac repair and regeneration. Recently, we identified a cardiac progenitor population that arises from the proepicardial organ in mice during embryonic development. These progenitor cells, which express the T-Box transcription factor Tbx18, migrate onto the surface of heart, form epicardium and then make a substantial contribution to cardiomyocytes, cardiac fibroblasts and coronary smooth muscle cells. Using an in vitro culture system, we also found Tbx18+ proepicardial cells can differentiate into multiple cardiac lineages. These observations led us to hypothesize that Tbx18-expressing epicardial cells are multipotent cardiac progenitors and that they can provide a cellular source for cardiac repair and regeneration for CVD patients. To test these hypotheses, our specific aims are: 1) To determine fates of Tbx18+ epicardial cells at late gestation and adult heart in mouse. 2) To determine whether Tbx18+ epicardial cells derived from late gestation and adult mouse hearts retain the potential to differentiate into different cardiac lineages in vitro. 3) To determine whether Tbx18+ epicardial cells in the injured mouse heart are able to convert to different cardiac lineages and improve cardiac function in vivo. Results of these studies will determine the multipotency of Tbx18+ epicardial cells at embryonic and adult stages in mouse, providing critical insights concerning the therapeutic potential of these cells for cardiac repair and regeneration in CVD patients.