Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells

TLDR

Cardiomyocyte regeneration is limited in adult life. The study seeks to identify adipose tissue as a source of cardiomyocyte progenitors by investigating the emergence of cardiomyocyte phenotype from adipose‑derived stromal cells. Adipose‑derived stromal cells were cultured and differentiated into cardiomyocyte‑like cells, which were identified morphologically, by cardiac marker expression, immunocytochemistry, and ultrastructural analysis. Rare beating cells with cardiomyocyte features emerged without 5‑azacytidine, displaying pacemaker activity, adrenergic‑stimulated beating, and cholinergic‑inhibited beating, demonstrating functional cardiomyocyte‑like cells that could provide a useful progenitor source given the abundance of adipose tissue.

Abstract

Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating cells with cardiomyocyte features could be identified after culture of adipose stroma cells without addition of 5-azacytidine. The cardiomyocyte phenotype was first identified by morphological observation, confirmed with expression of specific cardiac markers, immunocytochemistry staining, and ultrastructural analysis, revealing the presence of ventricle- and atrial-like cells. Electrophysiological studies performed on early culture revealed a pacemaker activity of the cells. Finally, functional studies showed that adrenergic agonist stimulated the beating rate whereas cholinergic agonist decreased it. Taken together, this study demonstrated that functional cardiomyocyte-like cells could be directly obtained from adipose tissue. According to the large amount of this tissue in adult mammal, it could represent a useful source of cardiomyocyte progenitors.