当前位置: X-MOL 学术Stem Cell Res. Ther. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation.
Stem Cell Research & Therapy ( IF 7.1 ) Pub Date : 2020-06-17 , DOI: 10.1186/s13287-020-01752-1
Chao Gao 1, 2 , Xiaodong Wang 3 , Jian Lu 1, 2 , Zhilin Li 1, 2 , Haowen Jia 1, 2 , Minghao Chen 1, 2 , Yuchen Chang 1, 2 , Yanhong Liu 1, 2 , Peiyuan Li 1, 2 , Baotong Zhang 1, 2 , Xuezhi Du 1 , Feng Qi 1, 2
Affiliation  

Mesenchymal stem cells (MSCs) have become a promising candidate for cell-based immune therapy for acute rejection (AR) after heart transplantation due to possessing immunomodulatory properties. In this study, we evaluated the efficacy of soluble fibronectin-like protein 2 (sFgl2) overexpressing mesenchymal stem cells (sFgl2-MSCs) in inhibiting AR of heart transplantation in mice by regulating immune tolerance through inducing M2 phenotype macrophage polarization. The sFgl2, a novel immunomodulatory factor secreted by regulatory T cells, was transfected into MSCs to enhance their immunosuppressive functions. After being co-cultured for 72 h, the sFgl2-MSCs inhibited M1 polarization whereas promoted M2 of polarization macrophages through STAT1 and NF-κB pathways in vitro. Besides, the sFgl2-MSCs significantly enhanced the migration and phagocytosis ability of macrophages stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Further, the application potential of sFgl2-MSCs in AR treatment was demonstrated by heterotopic cardiac transplantation in mice. The tissue damage and macrophage infiltration were evaluated by H&E and immunohistochemistry staining, and the secretion of inflammatory cytokines was analyzed by ELISA. The results showed that sFgl2-MSCs injected intravenously were able to locate in the graft, promote the M2 polarization of macrophages in vivo, regulate the local and systemic immune response, significantly protect tissues from damaging, and finally prolonged the survival time of mice heart grafts. sFgl2-MSCs ameliorate AR of heart transplantation by regulating macrophages, which provides a new idea for the development of anti-AR treatment methods after heart transplantation.

中文翻译:

用sFgl2转染的间充质干细胞通过调节巨噬细胞活化来抑制小鼠心脏移植的急性排斥反应。

间充质干细胞(MSCs)由于具有免疫调节特性,已经成为心脏移植后基于细胞的急性排斥反应(AR)免疫疗法的有希望的候选者。在这项研究中,我们评估了可溶性纤连蛋白样蛋白2(sFgl2)过度表达间充质干细胞(sFgl2-MSCs)通过诱导M2表型巨噬细胞极化来调节免疫耐受,从而抑制小鼠心脏移植AR。sFgl2是一种由调节性T细胞分泌的新型免疫调节因子,已被转染到MSC中以增强其免疫抑制功能。共培养72小时后,sFgl2-MSCs通过STAT1和NF-κB途径抑制了M1极化,而促进了M2极化巨噬细胞。除了,sFgl2-MSCs显着增强了干扰素-γ(IFN-γ)和脂多糖(LPS)刺激的巨噬细胞的迁移和吞噬能力。此外,通过小鼠异位心脏移植证明了sFgl2-MSC在AR治疗中的应用潜力。通过H&E和免疫组织化学染色评估组织损伤和巨噬细胞浸润,并通过ELISA分析炎性细胞因子的分泌。结果表明,静脉注射的sFgl2-MSCs能够定位于移植物中,促进体内巨噬细胞的M2极化,调节局部和全身免疫反应,显着保护组织免受损害,并最终延长了小鼠心脏移植物的存活时间。sFgl2-MSC通过调节巨噬细胞改善心脏移植的AR,
更新日期:2020-06-17
down
wechat
bug