Jiang Hongjing, Sun Xuheng, Wu Yindi, Xu Jianyi, Xiao Cong, Liu Qing, Fang Lijun, Liang Yuanfeng, Zhou Jiahui, Wu Yueheng, Lin Zhanyi
School of Medicine, South China University of Technology, 510006, Guangzhou, Guangdong, China.
Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 510080, Guangzhou, Guangdong, China.
Mater Today Bio. 2024 Jul 9;27:101151. doi: 10.1016/j.mtbio.2024.101151. eCollection 2024 Aug.
Host remodeling of decellularized extracellular matrix (dECM) material through the appropriate involvement of immune cells is essential for achieving functional organ/tissue regeneration. As many studies have focused on the role of macrophages, only few have evaluated the role of regulatory T cells (Tregs) in dECM remodeling. In this study, we used a mouse model of traumatic muscle injury to determine the role of Tregs in the constructive remodeling of vascular-derived dECM. According to the results, a certain number of Tregs could be recruited after dECM implantation. Notably, using anti-CD25 to reduce the number of Tregs recruited by the dECM was significantly detrimental to material remodeling based on a significant reduction in the number of M2 macrophages. In addition, collagen and elastic fibers, which maintain the integrity and mechanical properties of the material, rapidly degraded during the early stages of implantation. In contrast, the use of CD28-SA antibodies to increase the number of Tregs recruited by dECM promoted constructive remodeling, resulting in a decreased inflammatory response at the material edge, thinning of the surrounding fibrous connective tissue, uniform infiltration of host cells, and significantly improved tissue remodeling scores. The number of M2 macrophages increased whereas that of M1 macrophages decreased. Moreover, Treg-conditioned medium further enhanced material-induced M2 macrophage polarization . Overall, Treg is an important cell type that influences constructive remodeling of the dECM. Such findings contribute to the design of next-generation biomaterials to optimize the remodeling and regeneration of dECM materials.
通过免疫细胞的适当参与对脱细胞细胞外基质（dECM）材料进行宿主重塑对于实现功能性器官/组织再生至关重要。由于许多研究都集中在巨噬细胞的作用上，只有少数研究评估了调节性T细胞（Tregs）在dECM重塑中的作用。在本研究中，我们使用创伤性肌肉损伤小鼠模型来确定Tregs在血管源性dECM的建设性重塑中的作用。根据结果，dECM植入后可招募一定数量的Tregs。值得注意的是，使用抗CD25来减少dECM招募的Tregs数量对材料重塑有显著损害，这是基于M2巨噬细胞数量的显著减少。此外，维持材料完整性和机械性能的胶原蛋白和弹性纤维在植入早期迅速降解。相比之下，使用CD28-SA抗体增加dECM招募的Tregs数量促进了建设性重塑，导致材料边缘的炎症反应减少、周围纤维结缔组织变薄、宿主细胞均匀浸润以及组织重塑评分显著提高。M2巨噬细胞数量增加而M1巨噬细胞数量减少。此外，Treg条件培养基进一步增强了材料诱导的M2巨噬细胞极化。总体而言，Treg是影响dECM建设性重塑的重要细胞类型。这些发现有助于设计下一代生物材料，以优化dECM材料的重塑和再生。
