异体皮肤移植有望解决大面积烧伤自体皮源不足的难题，移植排斥反应是目前面临的主要难点。课题组前期研究发现，高表达吲哚胺2,3-双加氧酶（IDO）的BMSCs可促使初始T细胞向Treg细胞分化，减轻异体皮肤排斥反应。最新研究证实， BMSCs是否表达IDO受局部微环境中TGF-β、IFN-γ、TNF-α等多种炎性因子调控，而富血小板纤维蛋白（PRF）被证实可持续释放多种炎性因子及生长因子，PRF是否可为BMSCs表达IDO发挥免疫调节能力提供微环境尚不清楚。本项目拟通过蛋白芯片技术研究PRF微环境对BMSCs中TGFR等多种炎性因子受体及下游分子表达及活化的影响，检测IDO表达活化及其对BMSCs发挥免疫调节能力的影响；同时在小鼠异体皮肤移植模型上观察富载BMSCs的PRF对排斥反应及皮肤存活的影响。本研究有望进一步揭示BMSCs发挥免疫调控的分子机制，为减轻异体皮肤移植排斥提供新策略。

Allogenous skin transplantation is expected to solve the problem of autologous skin deficiency in severely burned patients, while allotransplantation rejection is currently one of the major difficulties. Previous studies by our group showed that BMSCs that express high levels of indoleamine 2,3- dioxygenase (IDO) could promote the differentiation of naive T-cells into Treg-cells, leading to alleviated allogenic skin rejection. In recent studies, the expression of IDO in BMSCs has been found to be regulated by several inflammatory factors in the microenvironment, such as TGF-β, IFN-γ and TNF-α; also, the platelet-rich fibrin (PRF) has been confirmed to sustainably release a variety of inflammatory cytokines and growth factors. However, whether PRF could provide the microenvironment that enables BMSCs to express IDO and thus plays its immune regulation function remains unclear. This project aims to investigate the effect of PRF microenvironment on the expression and activation of the receptors and downstream molecules of certain inflammatory cytokines, such as TGFR, in BMSCs via protein chip technique, also to examine the effect of IDO’s expression and activation on BMSCs’ immune regulation ability. In the meantime, this study proposes to observe the effect of BMSC-rich PRF on skin allograft rejection and skin survival in an established mouse model. Hopefully, this study would further reveal the molecular mechanism of BMSCs in immune regulation, and thus provide a novel strategy for reducing skin allograft rejection.