Mesenchymal stem cells (MSCs) have emerged as promising candidates for immune modulation in various diseases that are associated with dysregulated immune responses like Graft-versus-Host-Disease (GVHD). MSCs are pleiotropic and the fate of MSCs following administration is a major determinant of their therapeutic efficacy. In this context, we here demonstrate that hypoxia preconditioned apoptotic MSCs (bone marrow (BM), Wharton Jelly (WJ)) bear more immune programming ability in a cellular model of acute Graft-versus-Host-Disease (aGVHD). To this purpose, we programmed MSCs by exposing them to hypoxia and inducing apoptosis both sequentially as well as simultaneously. Our findings demonstrated that WJ MSCs that were conditioned with indicated approaches simultaneously induced the differentiation of CD4+T-cell towards Tregs, enhanced Th2 effector, and concomitantly mitigated Th1 and Th17, with polarization of M1 effector macrophages towards their M2 phenotype, and more interestingly enhanced efferocytosis by macrophages indicated Th2 programming ability of MSCs programmed by conjunctional approaches Overall, our study highlights the potential of WJ-MSCs(HYP+APO), as a promising therapeutic strategy for immune-related disorders and underscores the importance of considering MSC apoptosis in optimizing MSCs-based cellular therapy protocols for enhanced therapeutic efficacy in aGvHD.

中文翻译：

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协同缺氧和细胞凋亡调理释放间充质干细胞在急性移植物抗宿主疾病中的卓越功效

间充质干细胞（MSC）已成为免疫调节的有希望的候选者，用于治疗与移植物抗宿主病（GVHD）等免疫反应失调相关的各种疾病。间充质干细胞具有多效性，给药后间充质干细胞的命运是其治疗效果的主要决定因素。在此背景下，我们在此证明缺氧预条件凋亡的间充质干细胞（骨髓（BM）、沃顿胶（WJ））在急性移植物抗宿主病（aGVHD）细胞模型中具有更强的免疫编程能力。为此，我们通过将 MSC 暴露于缺氧并依次或同时诱导细胞凋亡来对其进行编程。我们的研究结果表明，用所示方法处理的 WJ MSC 同时诱导 CD4+T 细胞向 Tregs 分化，增强 Th2 效应细胞，并同时减轻 Th1 和 Th17，同时 M1 效应巨噬细胞向 M2 表型极化，更有趣的是巨噬细胞增强的胞吞作用表明通过联合方法编程的 MSC 的 Th2 编程能力总体而言，我们的研究强调了 WJ-MSC（HYP+APO）作为免疫相关疾病的有前途的治疗策略的潜力，并强调了在免疫相关疾病中考虑 MSC 凋亡的重要性。优化基于 MSC 的细胞治疗方案，以增强 aGvHD 的治疗效果。