Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations STEM CELL RESEARCH & THERAPY Rennert, R. C., Sorkin, M., Januszyk, M., Duscher, D., Kosaraju, R., Chung, M. T., Lennon, J., Radiya-Dixit, A., Raghvendra, S., Maan, Z. N., Hu, M. S., Rajadas, J., Rodrigues, M., Gurtner, G. C. 2014; 5

Abstract

Pathophysiologic changes associated with diabetes impair new blood vessel formation and wound healing. Mesenchymal stem cells derived from adipose tissue (ASCs) have been used clinically to promote healing, although it remains unclear whether diabetes impairs their functional and therapeutic capacity.In this study, we examined the impact of diabetes on the murine ASC niche, as well as on the potential of isolated cells to promote neovascularization in vitro and in vivo. A novel single cell analytical approach was used to interrogate ASC heterogeneity and subpopulation dynamics in this pathologic setting.Our results demonstrate that diabetes alters the ASC niche in situ, and that diabetic ASCs are compromised in their ability to establish a vascular network both in vitro and in vivo. Moreover, these diabetic cells were ineffective in promoting soft tissue neovascularization and wound healing. Single cell transcriptional analysis identified a subpopulation of cells which was diminished in both type 1 and type 2 models of diabetes. These cells were characterized by the high expression of genes known to be important for new blood vessel growth.Perturbations in specific cellular subpopulations, visible only on a single cell level, represent a previously unreported mechanism for the dysfunction of diabetic ASCs. These data suggest that the utility of autologous ASCs for cell-based therapies in diabetic patients may be limited, and that interventions to improve cell function before application are warranted.

View details for DOI 10.1186/scrt468

View details for Web of Science ID 000338465500001