Abstract
AimsThere 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 ResultsWe 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, CD45pos cells grew with milder proteolysis, while CD45neg 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 CD45pos cells expressed CD45 initially and rapidly lost its expression while differentiating.ConclusionsOur 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.
Highlights
During the last decade there has been evidence supporting the regenerative capability of the adult heart, but the mechanism is still debated
Our results demonstrate that the left atrial appendage plays a role as a reservoir of multiple types of progenitor cells in murine adult hearts
Histology of the murine left atrial appendage Immunostaining revealed a vast number of small c-kitpos (CD117) cells [19] located in the myocardium between the cardiomyocytes, and as well in the epicardium and endocardium (Figure 1B)
Summary
During the last decade there has been evidence supporting the regenerative capability of the adult heart, but the mechanism is still debated. CPCs are a heterogenic group and are thought to be concentrated in specific areas of the heart, e.g. atria or epicardium [2,3].Non-myocyte cells are the predominant cell population of the heart in number: cardiomyocytes are estimated to constitute 75% of the normal myocardial tissue volume in murine hearts, but only 30–55% of the total cell number [4]. This enables great variability in the cellular composition between different cardiac structures. Epicardial cells retain, in adulthood, the potential to activate embryonic transcription factors in response to cardiac injury [7]
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