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间充质干细胞衍生的细胞外囊泡作为自身免疫性疾病中非编码RNA的治疗载体

Mesenchymal Stem Cell-Derived Extracellular Vesicles as Non-Coding RNA Therapeutic Vehicles in Autoimmune Diseases.

作者信息

Martinez-Arroyo Olga, Ortega Ana, Forner Maria J, Cortes Raquel

机构信息

Cardiometabolic and Renal Risk Research Group, INCLIVA Biomedical Research Institute, 46010 Valencia, Spain.

Internal Medicine Unit, Hospital Clinico Universitario, 46010 Valencia, Spain.

出版信息

Pharmaceutics. 2022 Mar 29;14(4):733. doi: 10.3390/pharmaceutics14040733.

Abstract

Autoimmune diseases (ADs) are characterized by the activation of the immune system against self-antigens. More common in women than in men and with an early onset, their incidence is increasing worldwide, and this, combined with their chronic nature, is contributing to an enlarged medical and economic burden. Conventional immunosuppressive agents are designed to alleviate symptoms but do not constitute an effective therapy, highlighting a need to develop new alternatives. In this regard, mesenchymal stem cells (MSCs) have demonstrated powerful immunosuppressive and regenerative effects. MSC-derived extracellular vesicles (MSC-EVs) have shown some advantages, such as less immunogenicity, and are proposed as novel therapies for ADs. In this review, we summarize current perspectives on therapeutic options for ADs based on MSCs and MSC-EVs, focusing particularly on their mechanism of action exerted through their non-coding RNA (ncRNA) cargo. A complete state-of-the-art review was performed, centralized on some of the most severe ADs (rheumatoid arthritis, autoimmune type 1 diabetes mellitus, and systemic lupus erythematosus), giving evidence that a promising field is evolving to overcome the current knowledge and provide new therapeutic possibilities centered on MSC-EVs and their role as ncRNA delivery vehicles for AD gene therapy.

摘要

自身免疫性疾病(ADs)的特征是免疫系统针对自身抗原被激活。女性比男性更常见且发病较早,其发病率在全球范围内呈上升趋势,再加上其慢性性质,导致医疗和经济负担不断加重。传统的免疫抑制剂旨在缓解症状,但并非有效的治疗方法,这凸显了开发新替代方案的必要性。在这方面,间充质干细胞(MSCs)已显示出强大的免疫抑制和再生作用。MSC衍生的细胞外囊泡(MSC-EVs)已显示出一些优势,如免疫原性较低,并被提议作为ADs的新型治疗方法。在本综述中,我们总结了基于MSCs和MSC-EVs的ADs治疗选择的当前观点,特别关注它们通过非编码RNA(ncRNA)负载发挥作用的机制。我们进行了一项全面的最新综述,聚焦于一些最严重的ADs(类风湿性关节炎、自身免疫性1型糖尿病和系统性红斑狼疮),证明了一个有前景的领域正在发展,以突破现有知识,并提供以MSC-EVs及其作为AD基因治疗的ncRNA递送载体的作用为中心的新治疗可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3433/9028692/b5285a7d85dc/pharmaceutics-14-00733-g001.jpg

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