Vascular regeneration and skeletal muscle repair induced by long-term exposure to SDF-1α derived from engineered mesenchymal stem cells after hindlimb ischemia

Autor: Jin-Ju Kim, Jae-Hyun Park, Hyeok Kim, Woo-Sup Sim, Seokbeom Hong, Yeon-Jik Choi, Hyo-Jin Kim, Soon Min Lee, Dongha Kim, Sun-woong Kang, Kiwon Ban, Hun-Jun Park
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Experimental and Molecular Medicine, Vol 55, Iss 10, Pp 2248-2259 (2023)
Druh dokumentu: article
ISSN: 2092-6413
DOI: 10.1038/s12276-023-01096-9
Popis: Abstract 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.
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