Human umbilical cord mesenchymal stem cell-derived TGFBI attenuates streptozotocin-induced type 1 diabetes mellitus by inhibiting T-cell proliferation

作者：Chushan Wu, Weijiang Liu, Yuanlin Liu, Tingting Xu, Man Li, Xue Li, Yang Wang, Guangyu Meng, Lu Li, Rongxiu Zheng, Yi Zhang · 发表于：Human Cell · 年份：2023 · DOI：10.1007/s13577-023-00868-9 · 被引用次数：15 · 研究领域：Mesenchymal stem cell research、Pancreatic function and diabetes、Tissue Engineering and Regenerative Medicine

MSCs have been demonstrated to have a great benefit for type 1 diabetes mellitus (T1DM) due to their strong immunosuppressive and regenerative capacity. However, the comprehensive mechanism is still unclear. Our previous study indicated that transforming growth factor beta induced (TGFBI) is highly expressed in human umbilical cord-derived mesenchymal stem or stromal cells (hUC-MSCs), which are also implicated in T1DM. In this study, we found that infusion of TGFBI knockdown hUC-MSCs displayed impaired therapeutic effects in T1DM mice and decreased immunosuppressive capability. TGFBI knockdown hUC-MSCs could increase the proportion of T-cell infiltration while increasing the expression of IFN-gamma and interleukin-17A in the spleen. In addition, we also revealed that hUC-MSC-derived TGFBI could repress activated T-cell proliferation by interfering with G1/S checkpoint CyclinD2 expression. Our results demonstrate that TGFBI plays a critical role in MSC immunologic regulation. TGFBI could be a new immunoregulatory molecule controlling MSC function for new treatments of T1DM. Schematic Representation of the Immunosuppression capacity of hUC-MSC by TGFBI.