胰岛移植是一种能够使1型糖尿病病人脱离胰岛素治疗的有效治疗措施。但自身免疫介导的损伤作用是胰岛移植物在体内长期存活的主要障碍之一。我们前期体外实验结果显示，骨髓内皮细胞大量表达CCL2（MCP1），并且骨髓内皮细胞与单核细胞共培养可促进单核细胞向M2型巨噬细胞分化。先前已有研究报道，CCL2对单核细胞具有趋化作用，M2型巨噬细胞能够介导Th2型免疫反应，具有免疫抑制、组织修复和抗炎作用。基于上述认识和工作基础，我们提出"骨髓内皮细胞包被胰岛形成复合移植物进行移植时，骨髓内皮细胞所形成的微环境能够促进被其分泌的CCL2所募集的单核细胞向M2型巨噬细胞的分化，从而诱导免疫抑制保护移植胰岛免受自身免疫损伤"这一新的科学假设。为证实这一科学假设，本研究将通过体内体外一系列的试验探讨骨髓内皮细胞调控宿主自身免疫反应保护移植胰岛的可能机制。其研究成果可以为将来骨髓内皮细胞用于胰岛移植提供理论基础。

Islet transplantation is considered an appropriate treatment to achieve insulin independence in type 1 diabetic patients. However, autoimmune mediated destruction is one of the major obstacles to the long-term survival of islet grafts in vivo. Recently, we found that bone marrow endothelial cells could secrete substantially high levels of CCL2（MCP1）and provide an instructive niche for the differentiation of M2 macrophages from monocytes. Furthermore, previous studies reported that CCL2 could efficiently recruit monocytes in vitro and in vivo, and that M2-type macrophages could promote Th2-type immune response. Based on those work, we hypothesize that bone endothelial cells could provide critical niches for promoting the differentiation of M2-type macrophages from recruited circulating monocytes in the composite grafts， and preventing autoimmune destruction of islet grafts by the immunosuppression. To test the hypothesis, this study will explore potential mechanisms of how bone endothelial cells protect islet grafts by modulating the host autoimmune response. The finding may provide theoretic foundation for the application of bone endothelial cells on islet transplantation.