Key result
Murine LAA contains a large cardiac progenitor cell reservoir comprising ~20% of total cells.
Why the study?
The anatomic source and phenotype of master cardiac progenitor cells in adult hearts remain uncertain despite their key role in cardiac regeneration.
The adult murine left atrial appendage serves as a significant reservoir for diverse cardiac progenitor cells capable of cardiomyocyte differentiation.
May guide preclinical regenerative models; leaves open human relevance of left atrial appendage progenitors.
AIMS: There is strong evidence supporting the claim that endogenous cardiac progenitor cells (CPCs) are key players in cardiac regeneration, but the anatomic source and phenotype of the master cardiac progenitors remains uncertain. Our aim was to investigate the different cardiac stem cell populations in the left atrial appendage (LAA) and their fates. METHODS AND RESULTS: We investigated the CPC content and profile of adult murine LAAs using immunohistochemistry and flow cytometry. We demonstrate that the LAA contains a large number of CPCs relative to other areas of the heart, representing over 20% of the total cell number. We grew two distinct CPC populations from the LAA by varying the degree of proteolysis. These differed by their histological location, surface marker profiles and growth dynamics. Specifically, CD45(pos) cells grew with milder proteolysis, while CD45(neg) cells grew mainly with more intense proteolysis. Both cell types could be induced to differentiate into cells with cardiomyocyte markers and organelles, albeit by different protocols. Many CD45(pos) cells expressed CD45 initially and rapidly lost its expression while differentiating. CONCLUSIONS: Our results demonstrate that the left atrial appendage plays a role as a reservoir of multiple types of progenitor cells in murine adult hearts. Two different types of CPCs were isolated, differing in their epicardial-myocardial localization. Considering studies demonstrating layer-specific origins of different cardiac progenitor cells, our findings may shed light on possible pathways to study and utilize the diversity of endogenous progenitor cells in the adult heart.
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Leinonen et al. (2013) studied Normal adult murine hearts. Enzymatic digestion (strong vs weak proteolysis) vs. No digestion / different digestion strengths was evaluated on Proportion and phenotype of cardiac progenitor cells in the left atrial appendage. The murine left atrial appendage contains a large reservoir of cardiac progenitor cells (over 20% of total cells), yielding two distinct populations based on the degree of enzymatic digestion.
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