Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, China.
J Surg Res. 2021 Sep;265:100-113. doi: 10.1016/j.jss.2021.02.057. Epub 2021 Apr 23.
Stem cell-based regenerative therapy is a novel approach to severe damaged skin. Perinatal tissues such as placenta are considered as promising alternatives. The present study aimed to investigate the effect of insulin-like growth factor-1 (IGF-1)-expressing placenta-derived mesenchymal stem cells (hPMSCs) on healing of burn wounds.
hPMSCs were isolated from human placenta, and IGF-1 was transducted into hPMSCs via lentivirus. Flow cytometry and MTT assay were performed to assess cell apoptosis and viability, respectively. Immunostaining of CK19 and ki67 was for evaluating epithelial differentiation ability and cell proliferation. For in vivo studies, we established a mouse model of scalding and performed local administration of IGF-1-expressing hPMSCs via subcutaneous injection. Wound histology was analyzed with H&E staining. The expression of fibrogenic cytokines was detected by western blot. The production of pro-inflammatory factors was measured by ELISA.
Overexpression of IGF-1 promoted cell proliferation and epithelial differentiation of hPMSCs in vitro and in vivo. Mice with burn injury displayed increased wound contraction and healing rates following treatment with IGF-1-expressing hPMSCs. There was less inflammatory infiltration and reduced collagen disposition in the presence of IGF-1 at the wound site. Administration of IGF-1-expressing hPMSCs suppressed inflammation by decreasing the levels of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Besides, IGF-1 increased VEGF expression, and decreased TGF-β1, collagen I and collagen III expressions in vivo.
IGF-1-expressing PMSCs promotes cell proliferation and epithelial differentiation, inhibits inflammation and collagen deposition, and thus contributes to wound healing.
基于干细胞的再生疗法是治疗严重受损皮肤的一种新方法。围产期组织如胎盘被认为是有前途的替代品。本研究旨在探讨表达胰岛素样生长因子-1（IGF-1）的胎盘间充质干细胞（hPMSCs）对烧伤创面愈合的影响。
从人胎盘分离 hPMSCs，通过慢病毒将 IGF-1 转导至 hPMSCs。通过流式细胞术和 MTT 测定分别评估细胞凋亡和活力。CK19 和 ki67 的免疫染色用于评估上皮分化能力和细胞增殖。对于体内研究，我们建立了烫伤小鼠模型，并通过皮下注射局部给予表达 IGF-1 的 hPMSCs。用 H&E 染色分析伤口组织学。通过 Western blot 检测纤维生成细胞因子的表达。通过 ELISA 测量促炎因子的产生。
IGF-1 的过表达促进了 hPMSCs 的体外和体内细胞增殖和上皮分化。烧伤损伤的小鼠在接受表达 IGF-1 的 hPMSCs 治疗后，伤口收缩和愈合率增加。在伤口部位存在 IGF-1 时，炎症浸润减少，胶原排列减少。给予表达 IGF-1 的 hPMSCs 可通过降低肿瘤坏死因子-α、白细胞介素-1β 和白细胞介素-6 等促炎细胞因子的水平来抑制炎症。此外，IGF-1 增加了 VEGF 的表达，降低了 TGF-β1、胶原 I 和胶原 III 的表达。
表达 IGF-1 的 PMSCs 可促进细胞增殖和上皮分化，抑制炎症和胶原沉积，从而促进伤口愈合。
