Department of Molecular Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Cell Tissue Bank. 2022 Dec;23(4):923-936. doi: 10.1007/s10561-022-10007-7. Epub 2022 May 19.
The aim of this research is to compare the capabilities of Adipose tissue mesenchymal stem cells (AT-MSCs) and bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of diabetic male mice with CLI model. Supernatants were collected from C57BL/6 mice isolated AT-MSCs and BM-MSCs, afterward their effects on human umbilical vein endothelial (HUVEC) migration potential were evaluated. Diabetes mellitus type 1 was induced by streptozotocin injection. Diabetic mice with CLI model were divided into three groups and injected with AT-MSCs, BM-MSCs, or PBS then the efficacy of them was assessed. Survival of MSCs was analysed by SRY-specific gene. The conditioned medium of AT-MSCs and BM-MSCs stimulated HUVECs migration and the donor cells were detected till 21 day in two groups. BM-MSCs and AT-MSCs improved significantly functional recovery and ischemia damage. Neovascularization in ischemic muscle was significantly higher in mice treated with AT-MSCs and BM-MSCs and they improved muscle regeneration. In vivo and in vitro findings show that AT-MSCs and BM-MSCs transplantation could be proposed as a promising therapy to promote angiogenesis and muscle regeneration through secretion of proangiogenic factors, cytokines and growth factors in diabetic mice with CLI model wherein blood supply is insufficient and disrupted.
本研究旨在比较脂肪间充质干细胞(AT-MSCs)和骨髓间充质干细胞(BM-MSCs)在治疗伴有 CLI 模型的糖尿病雄性小鼠中的作用。从 C57BL/6 小鼠分离的 AT-MSCs 和 BM-MSCs 中收集上清液,评估其对人脐静脉内皮细胞(HUVEC)迁移潜能的影响。通过链脲佐菌素注射诱导 1 型糖尿病。将伴有 CLI 模型的糖尿病小鼠分为三组,分别注射 AT-MSCs、BM-MSCs 或 PBS,然后评估它们的疗效。通过性别决定区基因(SRY)特异性基因分析 MSCs 的存活情况。AT-MSCs 和 BM-MSCs 的条件培养基刺激 HUVEC 迁移,在两组中检测到供体细胞直到第 21 天。BM-MSCs 和 AT-MSCs 显著改善了功能恢复和缺血损伤。在接受 AT-MSCs 和 BM-MSCs 治疗的小鼠中,缺血肌肉中的新生血管明显增加,并且它们改善了肌肉再生。体内和体外研究结果表明,AT-MSCs 和 BM-MSCs 移植可作为一种有前途的治疗方法,通过分泌促血管生成因子、细胞因子和生长因子,促进糖尿病伴有 CLI 模型小鼠的血管生成和肌肉再生,在这些模型中,血液供应不足且受损。