获取足够的供体胰岛β样细胞是胰岛移植治疗1型糖尿病的关键，骨髓间充质干细胞（BMMSCs）可望成为分化β样细胞的理想来源，但提高其分化率是亟待解决的瓶颈问题。胰岛素瘤细胞外囊泡（Evs）能诱导BMMSCs分化为β样细胞，但其发挥诱导作用的确切成分及相关机制迄今未明。申请人课题组前期研究发现，Evs内含成分外泌体（Exos）较Evs具有更高的诱导β样细胞分化作用，且过表达CD97 Exos的诱导能力更强。申请人据此提出假说：Exos可能是Evs中诱导β样细胞分化的核心成分，CD97在该过程中发挥重要调控作用。本项目拟进一步明确胰岛素瘤Evs中Exos的诱导分化地位，论证并阐明CD97/MAPK/Smad/Ngn3通路（CD97/Ngn3轴）对该过程的调控作用。项目的实施将赋予Evs诱导BMMSCs成胰岛β样细胞分化新的科学依据与学术内涵，可望在胰岛移植供体高效获取的应用基础研究上有所突破。

Obtaining sufficient donor islet β-like cells is the key to islet transplantation for type 1 diabetes mellitus. Bone marrow mesenchymal stem cells (BMMSCs) are expected to be ideal sources to obtaining islet β-like cells, however the low differentiation rate is an urgent bottleneck that need to be solved. Extracellular vesicles (Evs) derived from insulinoma can differentiate BMMSCs into islet β-like cells, however the exact components and underlying mechanisms of their differentiation are not well studied. Previous studies of the applicant group have found that exosomes (Exos) had higher differentiation rate than Evs, and that the CD97 overexpressed Exos had higher differentiation rate than that of CD97 knockdown Exos. Therefore, the applicant propose the hypothesis that Exos may be the core component of Evs in differentiating BMMSCs into β-like cells, and that CD97 plays an important role in this process. The present project intends to further clarify the differentiation role of Exos in the Evs-induced β-like cell differentiation, and to clarify the regulation role of CD97/MAPK/Smad/Ngn3 pathway (CD97/Ngn3 axis) in the process. The implementation of this project can confer a new scientific basis and connotation of Evs-induced BMMSCs differentiation into islet β-like cells, which is expected to be a breakthrough in the basic research on obtaining islet transplantation donors.