Department of Cardiology, The Seventh Affiliated Hospital of Southern Medical University, Foshan, China.
Department of Family Medicine, College of Medicine, Dong-A University, Busan, Korea.
J Cell Mol Med. 2022 Jul;26(13):3726-3735. doi: 10.1111/jcmm.17401. Epub 2022 May 26.
Although stem cells have extensively been studied as a novel vehicle for tissue repair, their sustained efficacy remains controversial. In this study, we aimed to investigate the angiogenic potency over time of stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) in a hindlimb ischaemia model. An SDF-1 transgene was inserted into the AMM cell genome via transcription activator-like effector nuclease (TALEN) mediated knock-in, and cell migration, Matrigel tube formation, and in vivo Matrigel plug assays were performed. AMM/S were also transplanted into hindlimb ischaemia model mice. Blood perfusion, therapeutic potential, histology, capillary density and in vivo angiogenic assays were performed. AMM/S exhibited high expression of the SDF-1 gene, and robustly promoted migration, proliferation and microvascular formation. AMM/S transplantation significantly increased blood perfusion and limb loss prevention compared with AMM. AMM/S also significantly inhibited increased capillary density and expression of angiogenic factors in the ischaemic hindlimb. Our study demonstrated that AMM/S provides a significant therapeutic effect in ischaemic hindlimbs by enhancing angiogenesis.
虽然干细胞作为组织修复的新型载体已被广泛研究，但它们的持续疗效仍存在争议。在这项研究中，我们旨在研究基质细胞衍生因子 1（SDF-1）基因编辑羊膜间充质干细胞（AMM/S）在下肢缺血模型中的长期血管生成能力。通过转录激活因子样效应物核酸酶（TALEN）介导的基因敲入将 SDF-1 转基因插入 AMM 细胞基因组中，并进行细胞迁移、Matrigel 管形成和体内 Matrigel 塞检测。还将 AMM/S 移植到下肢缺血模型小鼠中。进行了血液灌注、治疗潜力、组织学、毛细血管密度和体内血管生成检测。AMM/S 表现出 SDF-1 基因的高表达，并强烈促进迁移、增殖和微血管形成。与 AMM 相比，AMM/S 移植显著增加了血液灌注并预防了肢体丧失。AMM/S 还显著抑制了缺血后肢中毛细血管密度和血管生成因子表达的增加。我们的研究表明，AMM/S 通过增强血管生成为缺血性后肢提供了显著的治疗效果。
