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 BM-MSCs transplantation on angiogenesis in a rat model of unilateral peripheral vascular disease. Materials and Methods: Twenty-one rats were arbitrarily allocated into three groups (۷/group). Group I: control sham-operated 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, ۲۴ hr after ligation, they were intramuscularly injected with BM-MSCs. After scarification, gastrocnemius muscle gene expression of stromal cell-derived factor-۱ (SDF-۱), CXC chemokine receptor ۴ (CXCR۴), vascular endothelial growth factor receptor ۲ (VEGFR۲), von Willebrand factor (vWF), and hypoxia-inducible factor-۱α (HIF-۱α) were analyzed by quantitative real-time PCR. Muscle regeneration and angiogenesis evaluation was assessed through H&E staining of the tissue. Furthermore, Pax۳ and Pax۷ nuclear expression was immunohistochemically assessed. Results: Rats treated with BM-MSCs showed significantly raised gene expression levels of SDF-۱, CXCR۴, VEGFR۲, 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 BM-MSCs showed cells demonstrating nuclear expression of Pax۳ and Pax۷. Conclusion: BM-MSCs 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-۱, CXCR۴, VEGFR۲, and vWF, decreased HIF-۱α gene expression, and increased myogenic Pax۷ gene expression.

Keywords:

CXC chemokine receptor ۴ , Mesenchymal stem cells , Peripheral vascular disease , Vascular endothelial growth factor receptor ۲ , Von Willebrand factor