Abstract：
Mesenchymal Stem Cells (MSCs) are of interest in the clinic because of their immunomodulation capabilities, capacity to act upstream of inflammation, and ability to sense metabolic environments. In standard physiologic conditions, they play a role in maintaining the homeostasis of tissues and organs; however, there is evidence that they can contribute to some autoimmune diseases. Gaining a deeper understanding of the factors that transition MSCs from their physiological function to a pathological role in their native environment, and elucidating mechanisms that reduce their therapeutic relevance in regenerative medicine, is essential. We conducted a Systematic Review and Meta-Analysis of human MSCs in preclinical studies of autoimmune disease, evaluating 60 studies that included 845 patient samples and 571 control samples. MSCs from any tissue source were included, and the study was limited to four autoimmune diseases: multiple sclerosis, rheumatoid arthritis, systemic sclerosis, and lupus. We developed a novel Risk of Bias tool to determine study quality for in vitro studies. Using the International Society for Cell & Gene Therapy\'s criteria to define an MSC, most studies reported no difference in morphology, adhesion, cell surface markers, or differentiation into bone, fat, or cartilage when comparing control and autoimmune MSCs. However, there were reported differences in proliferation. Additionally, 308 biomolecules were differentially expressed, and the abilities to migrate, invade, and form capillaries were decreased. The findings from this study could help to explain the pathogenic mechanisms of autoimmune disease and potentially lead to improved MSC-based therapeutic applications.
摘要：
间充质干细胞（MSCs）由于其免疫调节能力而在临床上受到关注，在炎症上游起作用的能力，和感知代谢环境的能力。在标准生理条件下，它们在维持组织和器官的稳态方面发挥作用；然而，有证据表明它们可以导致一些自身免疫性疾病。更深入地了解将MSCs从其生理功能转变为其天然环境中的病理作用的因素，并阐明降低其在再生医学中的治疗相关性的机制，是必不可少的。我们在自身免疫性疾病的临床前研究中对人MSCs进行了系统评价和Meta分析。评估60项研究，包括845例患者样本和571例对照样本。包括来自任何组织来源的MSC，这项研究仅限于四种自身免疫性疾病：多发性硬化症，类风湿性关节炎,系统性硬化症,和狼疮。我们开发了一种新的风险偏差工具来确定体外研究的研究质量。使用国际细胞和基因治疗协会的标准来定义MSC，大多数研究报告在形态上没有差异，附着力,细胞表面标记，或者分化为骨骼，脂肪，或软骨时，比较对照和自身免疫MSC。然而,据报道，增殖存在差异。此外,308个生物分子差异表达，以及迁移的能力，入侵,毛细血管的形成减少。这项研究的发现可以帮助解释自身免疫性疾病的致病机制，并可能导致改善基于MSC的治疗应用。
