Alterations in the Proangiogenic Functions of Adipose Tissue–Derived Stromal Cells Isolated from Diabetic Rats

Abstract

Cardiovascular complications in diabetic patients have been reported to be related to the impaired proangiogenic actions of endothelial progenitor cells. In this study, we investigated the functions of adipose tissue-derived stromal cells (ASCs) in diabetes. We induced type I diabetes in rats by a intraperitoneal injection of 60 mg/kg of streptozotocin (STZ) and type II diabetes by the combined treatment of high fat diet and 45 mg/kg of STZ. Rat ASCs (rASCs) isolated from the adipose tissues in the interscapular and abdominal region of type I or type II diabetic rats showed lower proliferating ability than those of control rats. Diabetic rASCs showed lower blood flow recovery than those of control rats in a hindlimb ischemia model of nude mouse. When ASCs isolated from rat and human were exposed to high glucose concentrations, their proliferating abilities and improved blood flow in a hindlimb ischemia model were compromised, compared with ASCs that were maintained at control glucose concentrations. However, the same concentrations of mannitol did not affect these characteristics. Exposure of human ASCs (hASCs) to high glucose concentrations increased reactive oxygen species (ROS) production, and the addition of ROS scavengers [N-acetylcysteine (NAC) or catalase] to high glucose media partially decreased the high glucose-induced inhibitory effect on proliferating ability in hASCs. However, hASCs treated with high glucose medium for 6 days showed lower proliferation in control culture medium, which was not recovered by the addition of NAC or catalase. These data indicate that ASCs isolated from diabetic rats and exposed at high concentration of glucose have an impaired proangiogenic action and that the functional impairment is partly due to ROS generated by chronic exposure to high glucose concentrations.