Bone Marrow Mesenchymal Stem Cells Overexpressing MicroRNA-126 to Treat Critical Limb Ischemia.

INTRODUCTION

Critical limb ischemia (CLI) is considered the most severe form of peripheral artery disease (PAD). Nowadays, using stem cells such as mesenchymal stem cells (MSCs) to induce angiogenesis seems like a promising method for CLI therapy. Among the many factors that affect the angiogenesis process, microRNA-126 has an important role.

OBJECTIVE

The goal of this study was to increase the angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) via using microRNA-126.

METHODS

BMSCs were isolated from male C57BL/6 inbred mice. CLI model was created by femoral artery ligation on C57BL/6 mice. Animals were allocated to control, BMSCs, miR-126, and BMSCsmiR-126 groups, and a defined number of the cells and virus were injected 24 h after surgery. Then, wound-healing assay, functional tests, real-time PCR, histopathological evaluation, and donor cell survival were performed.

RESULTS

Results showed that BMSCs and miR-126 groups had a positive effect on angiogenesis. BMSCs miR-126 group had a significant effect on functional improvements, endothelial cell migration, neovascularization, and muscle restructures. In vivo evaluation showed that miR-126 could increase BMSCs survival and paracrine secretion of angiogenic factors such as VEGF and led to remarkable functional improvements and neovascularization in ischemic tissues.

CONCLUSION

It can be concluded that the combination uses of BMSCs and miR-126 lead to more effective recovery from ischemic damage compared with using them alone. MiR-126 can be used as a strong modifier to reinforce the angiogenic potential, paracrine secretion, and survival of the BMSCs.