Progenitor cell transplantation has been considered as a potential angiogenesis therapy for the ischemic hindlimb. In this work we performed an ischemic hindlimb model in dogs. We ligated the middle sacra and the external right iliac arteries. After 7 days, the femoral artery was ligated and removed, and three Silastic tubes were inserted into the gracilis muscle to create fibrocollagenous tunnels. After Silastic implantation, we administered saline or granulocyte colony stimulating factor (G-CSF) subcutaneously daily during 5 days. Fourteen days after device positioning we transplanted bone marrow mononuclear cells (BMMC) into the tunnels previously formed by Silastic tube reaction. Twenty-eight days later, contrasted angiographies were performed and angiographic scores were calculated. Also, vessels and endothelial cells and proliferating cells were identified by immunochemistry of muscle sections. Results demonstrated that BMMC transplantation enriched by G-CSF administration significantly stimulates angiogenesis in the ischemic hindlimb, and more than BMMC transplantation alone. Transplantation of progenitor cells in an appropriate extracellular matrix is a potential therapy for hindlimb ischemia.
We established a comparative model of angiogenic induction in previously formed fibrocollagenous tunnels in rat inner thigh muscles. A unilateral hindlimb chronic ischemia model was performed in male Sprague-Dawley rats. A device was then inserted in the central portion of the inner thigh muscles. Vascularity in the ischemic limb was determined by means of an angiographic score, capillary/fiber ratio, and endothelial proliferation by histochemistry and immunohistochemistry. Autologous transplant of bone marrow, vascular endothelial growth factor (VEGF), or collagen-polyvinylpyrrolidone plus heparin induced significant vascularization of the ischemic hindlimb when compared to saline solution. However, the bone marrow group presented a higher angiographic score than the other two. No differences among groups were observed in capillary/fiber ratio or proliferation, except for the VEGF group, where capillary proliferating cells were significantly higher than in controls. Based on these results, bone marrow-derived progenitor cells may constitute a safe and viable alternative for the induction of therapeutic angiogenesis.
Bone marrow is an important supply for many progenitor cells, among them endothelial precursor cells. They have been already considered as potential therapeutic angiogenesis for ischemic hindlimb. In this work we performed an unilateral chronic ischemic hindlimb model in 20 dogs, we were dissected and ligated the middle sacra artery and external right iliac artery preserving the internal iliac artery, after one week we removed de femoral artery performing a proximal and distal ligation and inserted into the gracilis muscle 3 Silastic tubes (0.8 mm diameter) in a middle circle form in order to created fibrocollagenous tunnels. Fifteen days later, we obtained bone marrow (30 mL) and mononuclear cells were separated; at the same time, all tubes were removed and bone marrow cells were transplanted into the fibrocollagenous tunnels, only in the third and fourth groups. During the 8 at 12 days we administered subcutaneously saline solution to the first and third groups and G‐CSF to the second and fourth groups. Finally, after 30 days we performed contrasted angiographies from both limbs and was calculated mean angiographic score (MAS) from the number of vascular intersections, also was taken a biopsy from the central portion of right gracilis muscle for vascular assessment, as well as for vascular proliferating cells by immunohistochemistry. Results demonstrated that white bone marrow cell transplantation enrichment by G‐CSF administration stimulates angiogenesis in ischemic hindlimb, twice than controls, and it is better than white bone marrow cell transplantation alone. White bone marrow cell is a potential therapy for ischemic hindlimb, because stem cells are growth factor provider, as well as an important source for endothelial precursors capable to form vessels de novo, mainly when this stem cells are deposited in an appropriate extracellular matrix, such as the fibrocollagenous tunnels in this model.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.