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

Abstract

Background: 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.

Keywords: Angiogenesis; BMSCs; Critical limb Ischemia.; MicroRNA-126; Stem cell therapy; gene therapy.