Left Atrial Appendage—an Untapped Source for Cardiac Repair after Myocardial Infarction

Cardiac regenerative biology has been under intense research during the last decade, but the exact biological mechanism by which resident cells may regenerate cardiac tissue has remained elusive. Recent studies have suggested cardiomyocyte dedifferentiation and c-kit+ cardiac stem cells as key players in cardiac regenerative responses. We identified a vast population of diverse cardiac progenitor cells (CPCs) in the left atrial appendages of adult mice (Leinonen et al, 2013).We aim to characterize the LAA as a source of intrinsic CPCs that may serve as an endogenous source of cells for cardiac repair, as well as a therapeutic tool in myocardial infarction; to demonstrate that the LAA can deliver a “complete package” of regeneration; to understand mechanisms which activate intrinsic repair mechanisms; and to demonstrate that the appendage can be used as a “biological Band Aid” in the setting of a myocardial infarction. We have found that the atrial appendages contain a significant amount of diverse c-Kitpos CPCs, defined by their genetic blueprint using gene array with RNAseq confirmation, and by their embryonic origin by lineage tracing. We have produced three different types of cardiac progenitor cells from the atrial appendages and after the isolation of these cell types and assessment of their respective embryonic origins, we explored their phenotypic alterations and interactions with each other. Implantation of the LAA as a patch over an infarcted area produced significant improvements in LV remodeling and function using echo. We conclude that the CPC originating from the LAA is a promising vehicle for myocardial repair.