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

• Published in: Iranian journal of basic medical sciences Vol. 24; no. 6; pp. 805 - 814
• Main Authors: Ali, Amani M El Amin, Ahmed, Amira S, El-Yasergy, Dina F, Abousarie, Moustafa A, Elsayed, Ramadan M, Mohammed, Yasmin E, Mohammed, Rahab A
• Format: Journal Article
• Language: English
• Published: Iran Mashhad University of Medical Sciences 01-06-2021
• Subjects: Angiogenesis; cxc chemokine receptor 4; Gene expression; Ischemia; mesenchymal stem cells; Original; peripheral vascular disease; Rodents; Stem cells; vascular endothelial growth factor receptor 2; von willebrand factor; Peripheral vascular disease; Vascular endothelial growth - factor receptor 2; von Willebrand factor; CXC chemokine receptor 4; Mesenchymal stem cells
• ISSN: 2008-3866; 2008-3874
• DOI: 10.22038/ijbms.2021.55861.12491

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.
Twenty-one rats were arbitrarily allocated into three groups (7/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, 24 hr after ligation, they were intramuscularly injected with BM-MSCs. After scarification, gastrocnemius muscle gene expression of stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor receptor 2 (VEGFR2), von Willebrand factor (vWF), and hypoxia-inducible factor-1α (HIF-1α) were analyzed by quantitative real-time PCR. Muscle regeneration and angiogenesis evaluation was assessed through H&E staining of the tissue. Furthermore, Pax3 and Pax7 nuclear expression was immunohistochemically assessed.
Rats treated with BM-MSCs 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 BM-MSCs showed cells demonstrating nuclear expression of Pax3 and Pax7.
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-1, CXCR4, VEGFR2, and vWF, decreased HIF-1α gene expression, and increased myogenic Pax7 gene expression.