The immunomodulatory potential of mesenchymal stromal cells (MSCs) and regulatory T cells (T‐reg) is well recognized by translational scientists in the field of regenerative medicine and cellular therapies. A wide range of preclinical studies as well as a limited number of human clinical trials of MSC therapies have not only shown promising safety and efficacy profiles but have also revealed changes in T‐reg frequency and function. However, the mechanisms underlying this potentially important observation are not well understood and, consequently, the optimal strategies for harnessing MSC/T‐reg cross‐talk remain elusive. Cell‐to‐cell contact, production of soluble factors, reprogramming of antigen presenting cells to tolerogenic phenotypes, and induction of extracellular vesicles (“exosomes”) have emerged as possible mechanisms by which MSCs produce an immune‐modulatory milieu for T‐reg expansion. Additionally, these two cell types have the potential to complement each other's immunoregulatory functions, and a combinatorial approach may exert synergistic effects for the treatment of immunological diseases. In this review, we critically assess recent translational research related to the outcomes and mechanistic basis of MSC effects on T‐reg and provide a perspective on the potential for this knowledge base to be further exploited for the treatment of autoimmune disorders and transplants.

中文翻译：

---

间充质基质细胞对调节性 T 细胞的影响：目前的理解和临床相关性

间充质基质细胞 (MSC) 和调节性 T 细胞 (T-reg) 的免疫调节潜力得到了再生医学和细胞疗法领域的转化科学家的充分认可。广泛的临床前研究以及数量有限的 MSC 疗法人体临床试验不仅显示出有希望的安全性和有效性特征，而且还揭示了 T-reg 频率和功能的变化。然而，这一潜在重要观察背后的机制尚不清楚，因此，利用 MSC/T-reg 串扰的最佳策略仍然难以捉摸。细胞间接触、可溶性因子的产生、抗原呈递细胞重编程为致耐受表型、和诱导细胞外囊泡（“外泌体”）已成为 MSCs 为 T-reg 扩增产生免疫调节环境的可能机制。此外，这两种细胞类型具有互补免疫调节功能的潜力，组合方法可能对免疫疾病的治疗发挥协同作用。在这篇综述中，我们批判性地评估了最近与 MSC 对 T-reg 影响的结果和机制基础相关的转化研究，并提供了对该知识库进一步开发用于治疗自身免疫性疾病和移植的潜力的看法。并且组合方法可能对免疫疾病的治疗产生协同作用。在这篇综述中，我们批判性地评估了最近与 MSC 对 T-reg 影响的结果和机制基础相关的转化研究，并提供了对该知识库进一步开发用于治疗自身免疫性疾病和移植的潜力的看法。并且组合方法可能对免疫疾病的治疗产生协同作用。在这篇综述中，我们批判性地评估了最近与 MSC 对 T-reg 影响的结果和机制基础相关的转化研究，并提供了对该知识库进一步开发用于治疗自身免疫性疾病和移植的潜力的看法。