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体内间充质干细胞向烧伤损伤部位的迁移及其在活体小鼠模型中的治疗效果。

In vivo migration of mesenchymal stem cells to burn injury sites and their therapeutic effects in a living mouse model.

机构信息

Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, South Korea; Department of Plastic and Reconstructive Surgery, Kyungpook National University Hospital, Daegu, South Korea; Cell & Matrix Research Institute, Kyungpook National University, Daegu, South Korea.

Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.

出版信息

J Control Release. 2018 Jun 10;279:79-88. doi: 10.1016/j.jconrel.2018.04.020. Epub 2018 Apr 12.

Abstract

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for tissue regeneration and repair. In this study, we non-invasively monitored the tracking of MSCs toward burn injury sites using MSCs expressing firefly luciferase (Fluc) gene in living mice, and evaluated the effects of the MSCs at the injury site. Murine MSCs co-expressing Fluc and green fluorescent protein (GFP) were established using a retroviral system (referred to as MSC/Fluc). To evaluate the ability of MSC migration toward burn injury sites, cutaneous burn injury was induced in the dorsal skin of mice. MSC/Fluc was intravenously administrated into the mice model and bioluminescence imaging (BLI) was performed to monitor MSC tracking at designated time points. BLI signals of MSC/Fluc appeared in burn injury lesions at 4 days after the cell injection and then gradually decreased. Immunoblotting analysis was conducted to determine the expression of neovascularization-related genes such as TGF-β1 and VEGF in burnt skin. The levels of TGF-β1 and VEGF were higher in the MSC/Fluc-treated group than in the burn injury group. Our observations suggested that MSCs might assist burn wound healing and that MSCs expressing Fluc could be a useful tool for optimizing MSC-based therapeutic strategies for burn wound healing.

摘要

间充质干细胞(MSC)为基础的治疗已成为组织再生和修复的有前途的治疗策略。在这项研究中,我们使用表达萤火虫荧光素酶(Fluc)基因的 MSC 对活鼠进行非侵入性监测,以跟踪 MSC 向烧伤损伤部位的迁移,并评估 MSC 在损伤部位的作用。使用逆转录病毒系统(称为 MSC/Fluc)建立了共表达 Fluc 和绿色荧光蛋白(GFP)的鼠 MSC。为了评估 MSC 向烧伤损伤部位迁移的能力,在鼠背部皮肤诱导皮肤烧伤。将 MSC/Fluc 静脉内给予该鼠模型,并在指定时间点进行生物发光成像(BLI)以监测 MSC 追踪。在细胞注射后 4 天,MSC/Fluc 的 BLI 信号出现在烧伤损伤病变中,然后逐渐降低。进行免疫印迹分析以确定在烧伤皮肤中与新血管生成相关的基因(如 TGF-β1 和 VEGF)的表达。在 MSC/Fluc 处理组中,TGF-β1 和 VEGF 的水平高于烧伤损伤组。我们的观察结果表明,MSC 可能有助于烧伤伤口愈合,并且表达 Fluc 的 MSC 可能是优化基于 MSC 的烧伤伤口愈合治疗策略的有用工具。

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