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Open Access Highly Accessed Research

Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations

Robert C Rennert1, Michael Sorkin1, Michael Januszyk1, Dominik Duscher1, Revanth Kosaraju1, Michael T Chung1, James Lennon1, Anika Radiya-Dixit1, Shubha Raghvendra1, Zeshaan N Maan1, Michael S Hu1, Jayakumar Rajadas2, Melanie Rodrigues1 and Geoffrey C Gurtner1*

Author Affiliations

1 Hagey Laboratory for Pediatric Regenerative Medicine; Department of Surgery, Stanford University School of Medicine, 257 Campus Drive West, Hagey Building GK-201, Stanford, CA 94305-5148, USA

2 Biomaterials and Advanced Drug Delivery Center, Stanford University, 1050 Arastradero Road, building A, Room A163 Palo Alto, Stanford, CA 94304, USA

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Stem Cell Research & Therapy 2014, 5:79  doi:10.1186/scrt468

Published: 18 June 2014

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusions

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 patients with diabetes may be limited and that interventions to improve cell function before application are warranted.