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基于间充质干细胞的FGF2基因疗法对小鼠脂多糖诱导的急性肺损伤的作用

Mesenchymal stem cell-based FGF2 gene therapy for acute lung injury induced by lipopolysaccharide in mice.

作者信息

Zhao Y-F, Luo Y-M, Xiong W, Ding W, Li Y-R, Zhao W, Zeng H-Z, Gao H-C, Wu X-L

机构信息

Department of Respiratory Medicine, Pudong New Area, Gongli Hospital, Shanghai, P.R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2015;19(5):857-65.

Abstract

OBJECTIVE

Bone marrow-derived mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. FGF2 (basic fibroblast growth factor) is a multifunctional growth factor and exhibits diverse function in different cell types, it also has pleiotropic effects in different tissues and organs, including potent angiogenic effects and an important role in the differentiation and function of the central nervous system. We hypothesized that MSC-based FGF2 gene therapy might be a potential therapeutic approach for lipopolysaccharide (LPS)-induced lung injury.

MATERIALS AND METHODS

MSCs were isolated from 6 week-old inbred male mice and transduced with the FGF2 gene, using a lentivirus vector.

RESULTS

In the in vivo mouse model, the LPS-induced lung injury was markedly alleviated in the group treated with MSCs carrying FGF2 (MSCs-FGF2), compared with groups treated with MSCs alone. The histopathological index of LPS-induced lung injury was improved after MSCs-based FGF2 gene treatment. The MSCs-FGF2 administration also reduced the level of inflammatory cytokines.

CONCLUSIONS

These results suggest that MSCs and FGF2 have a synergistic role in the treatment of LPS-induced lung injury.

摘要

目的

骨髓间充质干细胞(MSCs)可作为基因治疗的载体。成纤维细胞生长因子2(FGF2,即碱性成纤维细胞生长因子)是一种多功能生长因子,在不同细胞类型中发挥多种功能,在不同组织和器官中也具有多效性作用,包括强大的血管生成作用以及在中枢神经系统的分化和功能中起重要作用。我们推测基于间充质干细胞的FGF2基因治疗可能是脂多糖(LPS)诱导的肺损伤的一种潜在治疗方法。

材料与方法

从6周龄近交系雄性小鼠中分离出间充质干细胞,并用慢病毒载体转导FGF2基因。

结果

在体内小鼠模型中,与单独用间充质干细胞治疗的组相比,用携带FGF2的间充质干细胞(MSCs-FGF2)治疗的组中,LPS诱导的肺损伤明显减轻。基于间充质干细胞的FGF2基因治疗后,LPS诱导的肺损伤的组织病理学指标得到改善。给予MSCs-FGF2也降低了炎性细胞因子水平。

结论

这些结果表明,间充质干细胞和FGF2在治疗LPS诱导的肺损伤中具有协同作用。

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