Pro-angiogenic efficacy of transplanting endothelial progenitor cells for treating hindlimb ischemia in hyperglycemic rabbits

Abstract

Aims: To evaluate the effectiveness of endothelial progenitor cells (EPCs) therapy in ischemia with or without hyperglycemia.

Methods: Japanese White Rabbits were randomly assigned to three groups, group SH, hyperglycemia with sham therapy (n=10); group NE, normoglycemia with autologous EPCs transplantation therapy (n=12); and group HE, hyperglycemia with autologous EPCs transplantation therapy (n=12). Hyperglycemia was induced by injecting alloxan and sustained for 12weeks. Hindlimb ischemia was induced by complete excision of the femoral artery. Ex vivo-expanded EPCs were derived from autologous bone marrow and transplanted intermuscularily in the ischemic hindlimb. Fourteen days after transplantation, the indicators were determined.

Results: There is no difference of the functions of ex vivo-expanded EPCs from autologous bone marrow between normoglycemic and hyperglycemic groups. We found significant improvement in both EPCs transplantation therapy groups compared to sham, in terms of the angiogenesis index (8.62±1.36, 11.12±2.23, 12.35±2.97), capillary density (7.06±0.91, 13.51±1.16, 13.90±2.78), capillary to muscle fiber ratio (0.68±0.09, 0.96±0.11,0.89±0.10), muscle VEGF expression (0.22±0.07, 0.41±0.08, 0.38±0.07ng/g). We found no significant differences between hyperglycemic and normoglycemic EPCs therapy groups except for 5 pro-angiogenic genes that were upregulated in HE as compared to NE.

Conclusion: Ex vivo expanded EPCs from autologous bone marrow transplantation is an effective therapeutic method for hindlimb ischemia in rabbits regardless of glycemic state.

Keywords: EPCs; Hindlimb ischemia; Hyperglycemia; Neovascularization; Transplantation.