Systems biology approach to identify alterations in the stem cell reservoir of subcutaneous adipose tissue in a rat model of diabetes: effects on differentiation potential and function.

ABSTRACT

AIMS/HYPOTHESIS: Autologous progenitor cells represent a promising option for regenerative cell-based therapies. Nevertheless, it has been shown that ageing and cardiovascular risk factors such as diabetes affect circulating endothelial and bone marrow-derived progenitor cells, limiting their therapeutic potential. However, their impact on other stem cell populations remains unclear. We therefore investigated the effects of diabetes on adipose-derived stem cells (ASCs) and whether these effects might limit the therapeutic potential of autologous ASCs. METHODS: A systems biology approach was used to analyse the expression of genes related to stem cell identification in subcutaneous adipose tissue (SAT), the stromal vascular fraction and isolated ASCs from Zucker diabetic fatty rats and their non-diabetic controls. An additional model of type 2 diabetes without obesity was also investigated. Bioinformatic approaches were used to investigate the biological significance of these changes. In addition, functional studies on cell viability and differentiation potential were performed. RESULTS: Widespread downregulation of mesenchymal stem cell markers was observed in SAT of diabetic rats. Gene expression and in silico analysis revealed a significant effect on molecules involved in the maintenance of pluripotency and self-renewal, and on the alteration of main signalling pathways important for stem cell maintenance. The viability and differentiation potential of ASCs from diabetic rats was impaired in in vitro models and in in vivo angiogenesis. CONCLUSIONS/INTERPRETATION: The impact of type 2 diabetes on ASCs might compromise the efficiency of spontaneous self-repair and direct autologous stem cell therapy.