Yang Yu, Wang Yanwen, Li Li, Chen Fei, Zhang Peng
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Mol Med Rep. 2017 Aug;16(2):2061-2068. doi: 10.3892/mmr.2017.6806. Epub 2017 Jun 19.
Mesenchymal stem cells (MSCs) are now widely used in clinical cell‑based therapy due to their characteristics of low immunogenicity, multiple differentiation potency and the capability to modulate immune responses. However, accumulated research has indicated the absence of engrafted MSCs because of the increased immunogenicity of MSCs. Toll‑like receptors (TLRs) are essential for the innate immune response and regulating the biological function of MSCs. The present study used human umbilical cord‑derived MSCs (UCMSCs) and activated the TLR8 pathway of UCMSCs to study the role of TLR8 in mediating the immune status of UCMSCs. The results demonstrated that the activation of TLR8 increased both the proliferation of peripheral blood mononuclear cells (PBMCs) isolated from healthy human volunteers and the release of lactate dehydrogenase (LDH) in supernatant from the PBMC‑UCMSCs co‑culture system. Reverse transcription-quantitative polymerase chain reaction indicated that the TLR8 agonist increased the expression of many co‑stimulatory molecules and pro‑inflammatory genes, and flow cytometry indicated that activation of the TLR8 agonist increased co‑stimulation protein levels but reduced specific surface markers, as confirmed by the part loss of stemness of UCMSCs. Finally, TLR8 increased osteocyte differentiation but had no effect on chondrocyte and adipocyte differentiation. The current study indicated the implication to TLR8 as regulators of the immunogenicity of UCMSCs.
间充质干细胞（MSCs）因其低免疫原性、多向分化潜能以及调节免疫反应的能力，目前已广泛应用于临床细胞治疗。然而，越来越多的研究表明，由于MSCs免疫原性增加，其在体内难以成功植入。Toll样受体（TLRs）对先天免疫反应和调节MSCs的生物学功能至关重要。本研究使用人脐带间充质干细胞（UCMSCs），激活UCMSCs的TLR8信号通路，以研究TLR8在介导UCMSCs免疫状态中的作用。结果表明，激活TLR8可增加从健康人类志愿者分离的外周血单个核细胞（PBMCs）的增殖，以及PBMC-UCMSCs共培养体系上清液中乳酸脱氢酶（LDH）的释放。逆转录-定量聚合酶链反应表明TLR8激动剂可增加多种共刺激分子和促炎基因的表达，流式细胞术表明TLR8激动剂激活可增加共刺激蛋白水平，但降低特异性表面标志物，这也通过UCMSCs干性部分丧失得到证实。最后，TLR8可增加骨细胞分化，但对软骨细胞和脂肪细胞分化没有影响。本研究表明TLR8可作为UCMSCs免疫原性的调节因子。
