Myogenic differentiation and reparative activity of stromal cells derived from pericardial adipose in comparison to subcutaneous origin.

INTRODUCTION

Adipose tissue-derived stromal cells (ADSCs) are abundant and easy to obtain, but the diversity of differentiation potential from different locations may vary with the developmental origin of their mesenchymal compartment. We therefore aim to compare the myogenic differentiation and reparative activity of ADSCs derived from the pericardial tissue to ADSCs of subcutaneous origin.

METHODS

Pericardial and inguinal adipose tissues from Wistar rats were surgically obtained, and the stromal fraction was isolated after enzymatic digestion. The phenotypic epitopes of the resultant two types of ADSCs were analyzed with flow cytometry, and the expression of transcriptional factors was analyzed with immunostaining. Furthermore, their potential toward adipogenic, osteogenic, and myogenic differentiation also was compared. Finally, the reparative activity and the resultant functional benefits were examined by allograft transplantation into an infarcted model in rats.

RESULTS

ADSCs from two adipose sources showed identical morphology and growth curve at the initial stage, but inguinal ADSCs (ingADSCs) sustained significantly vigorous growth after 25 days of cultivation. Although both ADSCs shared similar immunophenotypes, the pericardial ADSCs (periADSC) intrinsically exhibited partial expression of transcription factors for cardiogenesis (such as GATA-4, Isl-1, Nkx 2.5, and MEF-2c) and more-efficient myogenic differentiation, but less competent for adipogenic and osteogenic differentiation. After in vivo transplantation, periADSCs exhibited significantly vigorous reparative activity evidenced by thickening of ventricular wall and pronounced vasculogenesis and myogenesis, although the majority of prelabeled cells disappeared 28 days after transplantation. The structural repair also translated into functional benefits of hearts after infarction.

CONCLUSIONS

Although two sources of ADSCs are phenotypically identical, pericADSCs constituted intrinsic properties toward myogenesis and vasculogenesis, and thus provided more potent reparative effects after transplantation; therefore, they represent an attractive candidate cell donor for cardiac therapy.