Universidad de los Andes, Centro de Investigaciones Biomédicas, Facultad de Medicina , Santiago de , Chile.
Expert Opin Drug Discov. 2014 May;9(5):555-66. doi: 10.1517/17460441.2014.897692. Epub 2014 Mar 22.
Patients with systemic lupus erythematosus (SLE) are at increased risk for premature death, particularly among young adults, and present dilemmas regarding drug efficacy versus toxicity. Novel therapeutic strategies have included the use of mesenchymal stem cell (MSC) therapies that are promising but still have limitations. In several disease models, it has become apparent that MSCs do not necessarily replace diseased tissues but rather exert complex paracrine effects that are mediated by their extracellular-secreted products.
In this review, the authors highlight the data on MSC treatment of SLE and related mechanisms of actions. This data includes the recent evidence that MSC-secreted factors such as extracellular microvesicles (MVs) are important mediators of MSC therapy. Among MVs, the authors delineate the role of exosomes as triggers of regenerative effects in target cells, mediated by transfer of proteins, mRNAs or microRNAs. The authors also outline some of the biological and regulatory restraints encountered by MSC therapy, in contrast to the potential advantages of MSC-derived exosomes as new therapeutic tools in SLE.
There is concern about reproducible data on the use of MSC therapy in rheumatic diseases and specifically SLE. Although most experts consider MSCs to be safe, there are still worries over donor variability, immune-mediated rejection, culture-induced senescence, loss of functional properties and genetic instability or eventual malignant transformation. MSC-released factors could avoid most limiting factors associated with cell therapy and are therefore expected to provide a new and safe therapeutic option at an affordable cost.
系统性红斑狼疮（SLE）患者的过早死亡风险增加，尤其是在年轻成年人中，这涉及到药物疗效与毒性之间的权衡。新的治疗策略包括使用间充质干细胞（MSC）疗法，这种疗法有前景，但仍存在局限性。在几种疾病模型中，已经很明显，MSC 不一定替代患病组织，而是通过其细胞外分泌产物发挥复杂的旁分泌作用。
在这篇综述中，作者强调了 MSC 治疗 SLE 及相关作用机制的数据。这些数据包括最近的证据表明，MSC 分泌的因子，如细胞外小泡（MVs），是 MSC 治疗的重要介质。在 MVs 中，作者阐述了外泌体作为触发靶细胞再生效应的作用，这是通过蛋白质、mRNA 或 microRNAs 的转移来介导的。作者还概述了 MSC 治疗所遇到的一些生物学和监管限制，与 MSC 衍生的外泌体作为 SLE 新的治疗工具的潜在优势形成对比。
在风湿性疾病，特别是 SLE 中使用 MSC 治疗的重复性数据令人担忧。尽管大多数专家认为 MSC 是安全的，但人们仍然担心供体变异性、免疫介导的排斥反应、培养诱导的衰老、功能特性的丧失、遗传不稳定性或最终的恶性转化。MSC 释放的因子可以避免与细胞治疗相关的大多数限制因素，因此有望提供一种新的、安全的、负担得起的治疗选择。
