Characterization of human adipose tissue-derived stem cells with enhanced angiogenic and adipogenic properties

Abstract

Autologous fat grafting is a popular method for soft tissue reconstructions but graft survival remains highly unpredictable. Supplementation of the graft with the stromal vascular fraction (SVF) or cultured adipose tissue-derived stem cells (ASCs) can enhance graft viability. In this study we have examined the phenotypic properties of a selected population of cells isolated from ASCs, with a view to determining their suitability for transplantation into grafts. ASCs were isolated from the SVF of human abdominal fat (n = 8 female patients) and CD146⁺ cells were selected using immunomagnetic beads. The angiogenic and adipogenic properties of the positively selected cells were compared with the negative fraction. CD146⁺ cells expressed the immunophenotypic characteristics of pericytes. With prolonged in vitro expansion, CD146^- cells exhibited increased population doubling times and morphological signs of senescence, whereas CD146⁺ cells did not. CD146⁺ cells expressed higher levels of the angiogenic molecules VEGF-A, angiopoietin-1 and FGF-1. Conditioned medium taken from CD146⁺ cells significantly increased formation of in vitro endothelial cell tube networks, whereas CD146^- cells did not. CD146⁺ cells could be differentiated into adipocytes in greater numbers than CD146^- cells. Consistent with this, differentiated CD146⁺ cells expressed higher levels of the adipocyte markers adiponectin and leptin. These results suggest that CD146⁺ cells selected from a heterogeneous mix of ASCs have more favourable angiogenic and adipogenic properties, which might provide significant benefits for reconstructive and tissue-engineering applications. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: Adipogenesis; adult stem cell; angiogenesis; fat grafting; pericyte; regeneration.