CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation.

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptorCTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.

异基因间充质干细胞（allo - MSCs）因其广泛的临床治疗应用，近期受到了越来越多的关注。尽管如此，许多研究表明，除非给予免疫抑制治疗以控制同种异体免疫反应，否则异基因间充质干细胞与较高的移植物排斥率相关。细胞毒性T淋巴细胞相关蛋白4（CTLA4）是一种在T细胞上表达的共抑制分子，可介导对T细胞功能的抑制。在此，我们研究了在模拟体内异基因间充质干细胞移植微环境的激活免疫系统中异基因间充质干细胞的成骨分化潜能，并探讨了辅助性T细胞受体CTLA4在此过程中的免疫调节作用。我们发现，在存在激活的免疫反应时，间充质干细胞的成骨分化受到抑制，并且异基因间充质干细胞中CTLA4的过表达抑制了免疫反应并促进了成骨分化。我们的研究结果支持CTLA4过表达的异基因间充质干细胞在骨组织工程中的应用。