Wu Xiao-Qiang, Yan Tian-Zhong, Wang Zhi-Wei, Wu Xuan, Cao Guang-Hui, Zhang Chan
Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
Immunol Lett. 2017 Nov;191:55-62. doi: 10.1016/j.imlet.2017.09.010. Epub 2017 Sep 28.
Microvesicles (MVs) are plasmalemmal vesicles that are released from various cells and regarded as a mediator of intermolecular communication. In present study, we aimed to evaluate the therapeutic efficacy of the bone marrow mesenchymal stem cells (BM-MSCs)-derived MVs in the mice kidney transplant model and explored the underlying mechanism.
BM-MSCs were isolated from C57BL/6 mice and identified using flow cytometry. In vivo allogenic kidney transplantation model of mice was performed between C57BL/6 mice (recipient) and BALB/c mice (donor). Recipient-type BM-MSC (0.1ml) or equal volume of medium as a control was injected i.v. 24h after kidney transplantation. Serum was collected for creatinine concentration detection at 14 d after transplantation. Dendritic cells (DCs) phenotype and miR-146a expression level in plant was identified. Immature DCs (iDCs) and mature DCs (mDCs) were derived from monocytes. MVs were separated from BM-MSCs.
BM-MSCs positive for CD29 (95.8%) and CD44 (94.7%) were cultured and confirmed to prolong the allogenic kidney graft survival in mice. Importantly, the expression of miR-146a increased significantly in DCs of BM-MSCs-treated allogenic kidney. Moreover, both BM-MSCs and MVs derived from BM-MSCs enhanced miR-146a expression in iDCs and mDCs in vitro. Furthermore, MVs substantially reduced IL-12 mRNA expression and IL-12 production of mDCs whereas this action was reversed by miR-146a silencing. MiR-146a silencing also abrogated the MVs-induced decrease in serum creatinine, reduction of immature DCs phenotype in transplant and increase in miR-146a expression level.
In summary, our data suggested that the BM-MSCs-derived MVs improved allogenic kidney transplantation survival through inhibiting DCs maturity by miR-146a.
微泡（MVs）是从各种细胞释放的质膜囊泡，被视为分子间通讯的介质。在本研究中，我们旨在评估骨髓间充质干细胞（BM-MSCs）来源的微泡在小鼠肾移植模型中的治疗效果，并探索其潜在机制。
从C57BL/6小鼠中分离出BM-MSCs，并使用流式细胞术进行鉴定。在C57BL/6小鼠（受体）和BALB/c小鼠（供体）之间建立小鼠体内同种异体肾移植模型。肾移植后24小时静脉注射受体型BM-MSC（0.1ml）或等体积的培养基作为对照。移植后14天收集血清检测肌酐浓度。鉴定植物中树突状细胞（DCs）的表型和miR-146a表达水平。未成熟DCs（iDCs）和成熟DCs（mDCs）来源于单核细胞。从BM-MSCs中分离出微泡。
培养的CD29阳性（95.8%）和CD44阳性（94.7%）的BM-MSCs被证实可延长小鼠同种异体肾移植的存活时间。重要的是，在BM-MSCs处理的同种异体肾的DCs中，miR-146a的表达显著增加。此外，BM-MSCs和BM-MSCs来源的微泡在体外均增强了iDCs和mDCs中miR-146a的表达。此外，微泡显著降低了mDCs的IL-12 mRNA表达和IL-12产生，而这种作用被miR-146a沉默所逆转。miR-146a沉默还消除了微泡诱导的血清肌酐降低、移植中未成熟DCs表型的减少以及miR-146a表达水平的增加。
总之，我们的数据表明，BM-MSCs来源的微泡通过miR-146a抑制DCs成熟，从而提高同种异体肾移植的存活率。
