Potentiated therapeutic angiogenesis by primed human mesenchymal stem cells in a mouse model of hindlimb ischemia

Background: Human bone marrow-derived mesenchymal stem cells (hMSCs) are advantageous for cell-based therapy to treat ischemic diseases owing to their capacity to secrete various paracrine factors with potent angiogenic activity. Materials & methods: In this study, we describe a method to increase secreted levels of VEGF and HGF from hMSCs without genetic modification. Results: We demonstrated that transplantation of primed hMSCs into ischemic limbs led to significantly greater improvements in tissue perfusion and limb salvage by increasing capillary formation compared with nonprimed hMSCs. The primed hMSCs also exhibited greater survival in vivo and secreted human VEGF and HGF in the ischemic tissue, supporting enhanced angiogenesis and cell survival. Conclusion: These findings indicate that priming hMSCs via methods described in this study enhances secretion of critical proangiogenic factors resulting in an enhanced therapeutic effect of cells for the treatment of ischemic diseases.