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

Carmen Lambert; Gemma Arderiu; Maria Teresa Béjar; Javier Crespo; Maribel Baldellou; Oriol Juan‐Babot; Lina Badimón

doi:10.1186/s13287-019-1460-1

November 29, 2019Stem Cell Research & TherapyOpen Access

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

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Why the study?

The composition and function of adipose tissue covering the heart are poorly known.

Structured PICO

P

Population

Human epicardial adipose tissue (ventricular myocardium and perivascular) obtained from 30 patients undergoing cardiac transplant surgery (3 excluded, final n=27), mean age 54, 19 men/11 women.

I

Intervention

In vitro analysis of adipose stem cells (ASCs) isolated from ventricular myocardium adipose tissue (VMAT) and perivascular adipose tissue (PVAT)

O

Outcome

Depot-specific angiogenic function and gene expression (VEGFA, COL18A1, TF) of resident ASCssurrogate

Resident adipose stem cells in human epicardial adipose tissue display depot-specific angiogenic functions, with perivascular ASCs showing higher VEGFA expression than ventricular myocardium ASCs.

Implication

May enhance angiogenic cell therapy via perivascular ASC selection; leaves open translation from animal epicardial models.

Abstract

BACKGROUND: The 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. METHODS: EAT 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. RESULTS: ASCs 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. CONCLUSION: Our 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.