Periosteum-derived mesenchymal stem cell alleviates renal fibrosis through mTOR-mediated Treg differentiation.
Periosteum-derived mesenchymal stem cell alleviates renal fibrosis through mTOR-mediated Treg differentiation.
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DOI：
10.1080/0886022x.2023.2212079
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发表时间：
2023-12
期刊：
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
作者：
间充质干细胞（Mesenchymal stem cells, MSCs）因其低免疫原性、强免疫调节和独特的肾保护功能而成为细胞治疗的热点。本研究旨在探讨骨膜来源的间充质干细胞（PMSCs）在缺血再灌注（IR）介导的肾纤维化中的作用。利用细胞增殖试验、流式细胞术、免疫荧光和组织学分析，将PMSCs与骨髓源性MSCs （BMSCs）在细胞特性、免疫调节和肾保护方面的差异进行了比较，BMSCs是细胞治疗中最常研究的干细胞。此外，通过RNA转录本5 '端测序（SMART-seq）和mTOR敲除小鼠研究了PMSC肾保护的机制。PMSCs的增殖和分化能力强于BMSCs。与骨髓间充质干细胞相比，PMSCs在减轻肾纤维化方面具有更好的效果。同时，PMSCs更有效地促进Treg分化。Treg衰竭实验表明Treg在抑制肾炎症中发挥重要作用，并在PMSC肾保护中发挥重要的中介作用。此外，SMART-seq结果表明，PMSCs可能通过mTOR途径促进Treg分化。体内和体外实验表明，PMSC抑制Treg的mTOR磷酸化。mTOR敲除后，PMSCs不能促进Treg分化。与骨髓间充质干细胞相比，PMSCs具有更强的免疫调节和肾保护作用，这主要是由于PMSC通过抑制mTOR途径促进Treg分化。
Mesenchymal stem cells (MSCs) are the hotspots of cellular therapy due to their low immunogenicity, potent immunoregulation, and unique renoprotection. The present study aimed to investigate the effects of periosteum-derived MSCs (PMSCs) in ischemia–reperfusion (IR)-mediated renal fibrosis. Using cell proliferation assay, flow cytometry, immunofluorescence, and histologic analysis, the differences in cell characteristics, immunoregulation, and renoprotection of PMSCs were compared to the bone marrow-derived MSCs (BMSCs), the most frequently studied stem cells in cellular therapy. In addition, the mechanism of PMSC renoprotection was investigated by 5′ end of the RNA transcript sequencing (SMART-seq) and mTOR knockout mice. The proliferation and differentiation capabilities of PMSCs were stronger than those of BMSCs. Compared with BMSCs, the PMSCs exerted a better effect on alleviating renal fibrosis. Meanwhile, the PMSCs more effectively promote Treg differentiation. Treg exhaustion experiment indicated that Tregs exerted an important effect on inhibiting renal inflammation and acted as a critical mediator in PMSC renoprotection. Additionally, SMART-seq results implied that the PMSCs promoted Treg differentiation, possibly via the mTOR pathway. In vivo and in vitro experiments showed that PMSC inhibited mTOR phosphorylation of Treg. After mTOR knockout, the PMSCs failed to promote Treg differentiation. Compared with BMSCs, the PMSCs exerted stronger immunoregulation and renoprotection that was mainly attributed to PMSC promotion for Treg differentiation by inhibiting the mTOR pathway.
影响因子：
5.5
作者：
Cheuk YC;Xu S;Zhu D;Luo Y;Chen T;Chen J;Li J;Shi Y;Zhang Y;Rong R
通讯作者：
Rong R
单核细胞骨髓源性抑制细胞中 mTOR 缺陷通过诱导同种异体移植耐受来保护小鼠同种异体心脏移植物
影响因子：
7.3
作者：
Li J;Chen J;Zhang M;Zhang C;Wu R;Yang T;Qiu Y;Liu J;Zhu T;Zhang Y;Rong R
通讯作者：
Rong R