VEGF gene transfected umbilical cord mesenchymal stem cells transplantation improve the lower limb vascular lesions of diabetic rats

J Diabetes Complications. 2015 Sep-Oct;29(7):872-81. doi: 10.1016/j.jdiacomp.2015.04.018. Epub 2015 May 2.

Abstract

Background: Previous studies had explored the therapeutic effect of hUC-MSCs transplantation on ischemia; in this study, we further assessed the effectiveness of VEGF over-expressed hUC-MSCs cells transplantation on vascular proliferation in lower limb ischemia model in type 2 diabetic rats.

Methods: hUC-MSCs cells were over-expressed with VEGF, and transplanted to lower limb ischemia rats model of type 2 diabetes.

Results: VEGF over-expression increased the hUC-MSCs cells proliferation activity and VEGF secretion. VEGF gene transfected hUC-MSCs transplantation increased VEGF expression at a high level throughout 4weeks in skeletal muscle tissues of rats. Importantly, the vascular proliferation and blood perfusion of VEGF over-expressed hUC-MSCs transplanted limb were significantly improved compared with those of control group. The expression levels of ERK, AKT, MMP2 and MMP9 in VEGF over-expressed hUC-MSCs transplantation group increased dramatically compared with control group, while TIMP1 and TIMP2 expression had no significant change.

Conclusion: VEGF over-expressed hUC-MSCs transplantation was more effective to stimulate angiogenesis and increase blood perfusion than the simply hUC-MSCs transplantation, as maybe a new choice to improve the lower limb vascular lesions of diabetics.

Keywords: Diabetes; Lower limb vascular lesion; Stem cells; Transplantation; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Diabetes Mellitus, Experimental / surgery
  • Diabetes Mellitus, Type 2 / surgery*
  • Diabetic Angiopathies / prevention & control
  • Diabetic Angiopathies / surgery*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Neovascularization, Physiologic / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Regional Blood Flow / physiology
  • Sensitivity and Specificity
  • Transfection
  • Umbilical Cord
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Vascular Endothelial Growth Factor A