Human Adipose Tissue-Derived Mesenchymal Stem Cells Improve Postnatal Neovascularization in a Mouse Model of Hindlimb Ischemia

Abstract

BACKGROUND/AIM: It has been reported that adipose tissue contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. In this study we evaluated the effect of culture-expanded mesenchymal stem cells (MSC) derived from adipose tissue on neovascularization and blood flow in an animal model of limb ischemia in immunodeficient mice. METHODS: MSC were cultured from human adipose tissue by collagenase digestion. Hindlimb ischemia was created by ligating the proximal femoral artery of male nude mice. Human adipose tissue stromal cells (hADSC) were transplanted one day or 7 days after ligation. RESULTS: During culture expansion of hADSC CD34 expression was downregulated. The laser Doppler perfusion index was significantly higher in the CD34(-), Flk-1(-), CD31(-) ADSC-transplanted group than in the control group, even when cells were transplanted 7 days after hindlimb ischemia. Histological examination showed that hADSC transplantation recovered muscle injury and increased vascular density, compared with the control group. The effect of hADSC was correlated with the number of transplanted cells, but not with the ratio of CD34 expression. In vitro, hADSC can form vessel-like structure and express von Willibrand Factor. Conditioned media from hADSC increased proliferation and inhibited apoptotic cell death in of human aortic endothelial cells. CONCLUSION: This study showed that hADSC can be an ideal source for therapeutic angiogenesis in ischemic disease.