Stem cells from human cardiac adipose tissue depots show different gene expression and functional capacities

Abstract

BackgroundThe composition and function of the adipose tissue covering the heart are poorly known. In this study, we have investigated the epicardial adipose tissue (EAT) covering the cardiac ventricular muscle and the EAT covering the left anterior descending artery (LAD) on the human heart, to identify their resident stem cell functional activity.MethodsEAT covering the cardiac ventricular muscle was isolated from the apex (avoiding areas irrigated by major vessels) of the heart (ventricular myocardium adipose tissue (VMAT)) and from the area covering the epicardial arterial sulcus of the LAD (PVAT) in human hearts excised during heart transplant surgery. Adipose stem cells (ASCs) from both adipose tissue depots were immediately isolated and phenotypically characterized by flow cytometry. The different behavior of these ASCs and their released secretome microvesicles (MVs) were investigated by molecular and cellular analysis.ResultsASCs from both VMAT (mASCs) and the PVAT (pASCs) were characterized by the expression of CD105, CD44, CD29, CD90, and CD73. The angiogenic-related genes VEGFA, COL18A1, and TF, as well as the miRNA126-3p and miRNA145-5p, were analyzed in both ASC types. Both ASCs were functionally able to form tube-like structures in three-dimensional basement membrane substrates. Interestingly, pASCs showed a higher level of expression of VEGFA and reduced level of COL18A1 than mASCs. Furthermore, MVs released by mASCs significantly induced human microvascular endothelial cell migration.ConclusionOur study indicates for the first time that the resident ASCs in human epicardial adipose tissue display a depot-specific angiogenic function. Additionally, we have demonstrated that resident stem cells are able to regulate microvascular endothelial cell function by the release of MVs.

Exploring the role of epicardial adipose-tissue-derived extracellular vesicles in cardiovascular diseases

“…Cell-based therapy (e.g., by combining human cardiac stem cells and bone marrow mesenchymal stromal cells) reduces scar size and represses adverse remodeling secondary to myocardial infarction in preclinical models 90 and in clinical trials of patients with ischemic cardiomyopathy. 91 EAT represents a depot of mesenchymal stromal cells possibly promoting cardiac regeneration following ischemic injury, 92 and so its potential role in aiding cardiac regeneration, particularly in response to ischemic insult, is an aspect worth considering. Administration of EVs isolated from adipose-derived mesenchymal stromal cells in rats subjected to ischemia/reperfusion injury significantly reduced size of myocardial infarction, along with serum levels of creatinine kinase-myocardial band, lactate dehydrogenase, and cardiac troponin I.…”

“…explored the distinct functional properties of the adipose stem cells contained in two different EAT locations in the heart of transplant-eligible patients with advanced heart failure. 92 EAT was isolated from the apex of the heart and the area covering the epicardial arterial sulcus of the left anterior descending artery. EVs released by adipose stem cells potentially have a role in mediating pro-angiogenic effects and spontaneous regeneration of damaged tissue, and it was demonstrated how this effect may vary according to the presence of cardiovascular risk factors such as obesity and diabetes.…”

Muscle and Adipose Tissue Communicate with Extracellular Vesicles

“…It is presently not known whether obesity alters these EV benefic properties. In addition, as stem cells from epicardiac and ventricular adipose tissue are different in terms of their proliferative and survival capacities, it would be interesting to determine whether their respective released EVs also have specific properties in cardiac muscle [39].…”

The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium

“…Most miRNAs on EAT operate through autocrine fashion and have been implicated in various AT processes such as adipocyte differentiation, fatty acid metabolism, cholesterol homeostasis, adipogenesis, browning and inflammation (183)(184)(185). Other miRNAs are released into the circulation via exosomes, from where they travel to and penetrate the heart or other distant organs (186).…”