免疫反应:干细胞再生疗法的致命弱点

C. S. Oliveira, F. Tavaria
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引用次数: 0

摘要

除了创伤,一些直接影响器官正常功能的病理状况需要新的治疗策略来修复受损或患病的组织。组织再生是一个复杂的时空过程,涉及过多的细胞类型,包括各种同步关系的免疫细胞和干细胞。然而,个体参数,即衰老、肥胖、糖尿病和慢性病,与成人组织的不良再生特性有着内在的相关性。尽管在基于干细胞的直接自我修复治疗方面取得了巨大进展,但免疫反应仍然是这些策略的致命弱点。尽管效应免疫细胞在再生过程中的作用已经得到了很好的定义,但了解主要成体干细胞,即间充质干细胞(MSC)和造血干细胞和祖细胞(HSPCs)在再生过程的不同阶段的行为,可以阐明这些干细胞如何被用来积极影响免疫反应。在这一范围内,这篇综述强调了这些干细胞和免疫细胞在组织修复过程中的主要相互作用,探索了干细胞最重要的再生特性,并将其与组织再生过程中免疫反应的调节联系起来。此外,还强调了用于探索行为和干细胞命运如何受到再生过程中通常发现的特定微环境和/或刺激的影响的最大策略。这一澄清可能为干细胞在组织修复的正反馈回路中调节免疫反应的分子机制提供关键的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Immune response: the Achilles’ heel of the stem cell-based regenerative therapies
Besides trauma, several pathological conditions which directly affect the normal functioning of organs, require new therapeutic strategies to repair damaged or diseased tissues. Tissue regeneration is a complex and spatiotemporal process involving a plethora of cell types, including various immune cells and stem cells in a synchronized relationship. However, individual parameters, namely ageing, obesity, diabetes, and chronic conditions, have been intrinsically correlated with poor regenerative properties of adult tissues. While vast progress has been made regarding stem cell-based therapy to direct self-healing, the immune response is still the Achilles’ heel of such strategies. Whereas the role of effector immune cells has been well defined along the regenerative process, an understanding of the behavior of the main adult stem cells, namely mesenchymal stem cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs), along the different phases of the regenerative process could clarify how these stem cells can be used to positively influence the immune response. In this scope, this review highlights the main interactions between these stem cells and immune cells during tissue repair, exploring the most important regenerative properties of stem cells and correlating them with the modulation of the immune response during tissue regeneration. Furthermore, the utmost strategies used to explore how the behavior and stem cell fate are affected by specific microenvironments and/or stimuli usually found during a regenerative process, are emphasized. This clarification may provide critical insight into the molecular mechanisms by which stem cells modulate the immune response in a positive feedback loop toward tissue repair.
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