Neovascular potential of adipose-derived stromal cells (ASCs) from diabetic patients

Abstract

We explored the vascular biology of adipose-derived stromal cells (ASCs) from diabetic patients and applied these cells to a murine ischemic flap model to assess the comparative angiogenic potentials between normal and diabetic human ASCs. ASCs were obtained from diabetic patients (n = 5) and controls (n = 5). Secretion and expression of angiogenic cytokines were measured under normoxic and hypoxic condition in vitro. Conditioned media harvested from ASC cultures were assessed for their ability to stimulate human umbilical vein endothelial cell proliferation and tubulization. The control and diabetic ASCs were injected into the murine ischemic flaps, and the surviving area was measured. Diabetic adipose-derived stromal cells showed a lower level of vascular endothelial growth factor expression and cell proliferation rates than the control cells (p < 0.05). However, vascular endothelial growth factor, hepatocyte growth factor secretion, tubulogenesis, and cell proliferation in diabetic conditioned media were increased in response to hypoxic stimuli (p < 0.05), and it was similar to those of control cells. In an animal study, diabetic and normal ASCs significantly increased flap survival (p < 0.05); however, the functional difference was not found between the two groups. Diabetic ASCs were impaired in their ability to produce vascular endothelial growth factors and to induce cellular proliferation under hypoxic conditions. However, diabetic ASCs showed similar flap salvaging effect compared with controls. These findings may be important in the context of future study of autologous cell-based therapy in diabetic patients.