Novel Regenerative Solutions Induce Rapid Adipogenic Differentiation of Mesenchymal Stem Cells with No Evidence of Transformation or Osteogenic Differentiation

Abstract

Adipose tissue is commonly used in plastic surgery procedures and is also a rich source of mesenchymal stem cells (MSCs). Since MSCs are functionally plastic cells, adipose tissue may provide a promising cell source for regenerative medicine applications. We have developed two mixed growth factor formulations (termed "dermal" and "fat" factor formulations) to be used with autologous adipose tissue to help induce the regeneration of human skin and subcutaneous tissue. In this study, we investigate the effect of these formulations on proliferation and differentiation of MSCs obtained from human bone marrow and from adipose tissues. Lower concentrations of both formulations had no effect on MSC proliferation, but induced rapid adipogenic differentiation. At higher concentrations, both formulations induced MSC death. There was no evidence of osteogenesis ormalignant transformation at any concentration, as judged by absence of foci formation, inability of the cells to be serially passaged and absence of colonies in methylcellulose matrix. Thus, at optimal doses these factor formulations promote rapid differentiation of MSCs into adipogenic cells, with no evidence of cell transformation or osteogenic induction. These studies have implications for wound healing and tissue regeneration, as well as cosmetic applications to enhance the deficits seen in aging skin and in facial volume loss.