Aged adipose derived stem cells are more proliferative and less responsive to differentiation cues

Abstract

Adipose derived stem cells (ADSCs) are mesenchymal stem cells that reside within the microvasculature of adipose tissue. Two questions regarding ADSCs that have not been adequately addressed are 1) whether the aging process adversely affects the potential of ADSCs for use in therapeutic applications and 2) whether age‐related changes in ADSCs contribute to increased adiposity observed in aging individuals. To address these questions, we obtained ADSCs from young and old rats and compared their ability to proliferate and differentiate into multiple cell lineages. ADSCs obtained from young and old animals exhibited the same phenotype; however, old ADSCs were more proliferative. When induced to undergo adipogenic or osteogenic differentiation, young ADSCs exhibited greater levels of staining for indicators of terminal differentiation and greater changes in the expression of several genes involved in differentiation. Our results suggest that ADSCs are subject to cell‐intrinsic aging mechanisms that render aged cells more proliferative and less responsive to differentiation cues than young cells even when cultured under identical conditions. This raises concern over the potential use of autologous ADSCs in therapeutic applications for elderly individuals and suggests that hyperproliferative ADSCs could play a role in the accumulation of adipose and adipose‐like tissue in aged individuals.