Unité de Recherche en Pharmaco-Immunologie (UR-EPI), Université et CHU de La Réunion, 97400 Saint-Denis, France.
Service de Médecine d'Urgences-SAMU-SMUR, CHU de La Réunion, 97400 Saint-Denis, France.
Int J Mol Sci. 2022 Aug 17;23(16):9274. doi: 10.3390/ijms23169274.
The treatment of sepsis and septic shock remains a major public health issue due to the associated morbidity and mortality. Despite an improvement in the understanding of the physiological and pathological mechanisms underlying its genesis and a growing number of studies exploring an even higher range of targeted therapies, no significant clinical progress has emerged in the past decade. In this context, mesenchymal stem cells (MSCs) appear more and more as an attractive approach for cell therapy both in experimental and clinical models. Pre-clinical data suggest a cornerstone role of these cells and their secretome in the control of the host immune response. Host-derived factors released from infected cells (i.e., alarmins, HMGB1, ATP, DNA) as well as pathogen-associated molecular patterns (e.g., LPS, peptidoglycans) can activate MSCs located in the parenchyma and around vessels to upregulate the expression of cytokines/chemokines and growth factors that influence, respectively, immune cell recruitment and stem cell mobilization. However, the way in which MSCs exert their beneficial effects in terms of survival and control of inflammation in septic states remains unclear. This review presents the interactions identified between MSCs and mediators of immunity and tissue repair in sepsis. We also propose paradigms related to the plausible roles of MSCs in the process of sepsis and septic shock. Finally, we offer a presentation of experimental and clinical studies and open the way to innovative avenues of research involving MSCs from a prognostic, diagnostic, and therapeutic point of view in sepsis.
由于相关发病率和死亡率，脓毒症和脓毒性休克的治疗仍然是一个主要的公共卫生问题。尽管人们对其发病机制的生理和病理机制的理解有所提高，并且越来越多的研究探索了更高范围的靶向治疗，但在过去十年中并没有出现重大的临床进展。在这种情况下，间充质干细胞 (MSCs) 在实验和临床模型中似乎越来越成为细胞治疗的一种有吸引力的方法。临床前数据表明，这些细胞及其分泌组在控制宿主免疫反应方面起着基石作用。源自感染细胞的宿主来源因子（即警报素、HMGB1、ATP、DNA）以及病原体相关分子模式（例如 LPS、肽聚糖）可以激活位于实质和血管周围的 MSC，上调细胞因子/趋化因子和生长因子的表达，分别影响免疫细胞募集和干细胞动员。然而，MSC 如何在脓毒症状态下发挥其生存和控制炎症的有益作用仍不清楚。这篇综述介绍了 MSC 与脓毒症中免疫和组织修复介质之间已确定的相互作用。我们还提出了与 MSC 在脓毒症和脓毒性休克过程中可能作用相关的范例。最后，我们介绍了实验和临床研究，并从预后、诊断和治疗的角度为涉及脓毒症的 MSC 的创新研究途径开辟了道路。
