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Vascular regeneration and skeletal muscle repair induced by long-term exposure to SDF-1α derived from engineered mesenchymal stem cells after hindlimb ischemia
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Vascular regeneration and skeletal muscle repair induced by long-term exposure to SDF-1α derived from engineered mesenchymal stem cells after hindlimb ischemia
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Journal Article
Vascular regeneration and skeletal muscle repair induced by long-term exposure to SDF-1α derived from engineered mesenchymal stem cells after hindlimb ischemia
2023
Overview
Despite recent progress in medical and endovascular therapy, the prognosis for patients with critical limb ischemia (CLI) remains poor. In response, various stem cells and growth factors have been assessed for use in therapeutic neovascularization and limb salvage in CLI patients. However, the clinical outcomes of cell-based therapeutic angiogenesis have not provided the promised benefits, reinforcing the need for novel cell-based therapeutic angiogenic strategies to cure untreatable CLI. In the present study, we investigated genetically engineered mesenchymal stem cells (MSCs) derived from human bone marrow that continuously secrete stromal-derived factor-1α (SDF1α-eMSCs) and demonstrated that intramuscular injection of SDF1α-eMSCs can provide long-term paracrine effects in limb ischemia and effectively contribute to vascular regeneration as well as skeletal muscle repair through increased phosphorylation of ERK and Akt within the SDF1α/CXCR4 axis. These results provide compelling evidence that genetically engineered MSCs with SDF-1α can be an effective strategy for successful limb salvage in limb ischemia.
Breakthrough in limb ischemia: the power of genetically modified MSCs
Researchers have developed a strategy using SDF1α-engineered mesenchymal stem cells (SDF1α-eMSCs) to simultaneously regenerate blood vessels and skeletal muscles in limbs experiencing ischemia. In a mouse model of hindlimb ischemia, intramuscular injection of SDF1α-eMSCs improved blood perfusion, preserved limb function, and prevented amputation. In vitro result showed that SDF1α-eMSCs not only amplified the angiogenic potential and survival of endothelial cells, but also demonstrated enhanced survival and migration abilities in myoblasts. The study suggests that SDF1α-eMSCs can be considered an effective therapeutic strategy for limb salvage in patients with critical limb ischemia.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group,생화학분자생물학회
Subject
/ 13/100
/ 13/21
/ 14/19
/ 64/60
/ 82/80
/ 96/31
/ Animals
/ Biomedical and Life Sciences
/ Chemokine CXCL12 - metabolism
/ Chemokine CXCL12 - pharmacology
/ Humans
/ Ischemia
/ Limbs
/ Mesenchymal Stem Cell Transplantation
/ Mesenchymal Stem Cells - metabolism
/ Muscle, Skeletal - metabolism
/ Neovascularization, Physiologic
/ Patients
/ 생화학
