Therapeutic potential of mesenchymal stem cells for peripheral artery disease in a rat model of hindlimb ischemia

Objective(s): Mesenchymal stem cells are viewed as the first choice in regenerative medicine. This study aimed to elucidate the influence of BMMSCs transplantation on angiogenesis in a rat model of unilateral peripheral vascular disease. Materials and Methods: Twentyone rats were arbitrarily allocated into three groups (7/group). Group I: control shamoperated rats, Group II: control ischemic group: Rats were subjected to unilateral surgical ligation of the femoral artery, and Group III: ischemia group:  Rats were induced as in group II, 24 hr after ligation, they were intramuscularly injected with BMMSCs. After scarification, gastrocnemius muscle gene expression of stromal cellderived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor receptor 2 (VEGFR2), von Willebrand factor (vWF), and hypoxiainducible factor-1α (HIF-1α) were analyzed by quantitative realtime PCR. Muscle regeneration and angiogenesis evaluation was assessed through H E staining of the tissue. Furthermore, Pax3 and Pax7 nuclear expression was immunohistochemically assessed. Results: Rats treated with BMMSCs showed significantly raised gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF compared with control and ischemia groups. H E staining of the gastrocnemius showed prominent new vessel formation. Granulation tissue within muscles of the ischemic treated group by BMMSCs showed cells demonstrating nuclear expression of Pax3 and Pax7. Conclusion: BMMSCs transplantation has an ameliorating effect on muscle ischemia through promoting angiogenesis, detected by normal muscle architecture restoration and new blood vessel formations observed by H E, confirmed by increased gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF, decreased HIF-1α gene expression, and increased myogenic Pax7 gene expression.