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间充质干细胞外泌体的单一及联合策略减轻肝纤维化:对临床前动物模型的系统评价和荟萃分析

Single and combined strategies for mesenchymal stem cell exosomes alleviate liver fibrosis: a systematic review and meta-analysis of preclinical animal models.

作者信息

Zhou Xiaolei, Xu Yan, Wang Xuesong, Lu Wenming, Tang Xingkun, Jin Yu, Ye Junsong

机构信息

Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.

School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, China.

出版信息

Front Pharmacol. 2024 Jul 31;15:1432683. doi: 10.3389/fphar.2024.1432683. eCollection 2024.

DOI:10.3389/fphar.2024.1432683
PMID:39144628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11322148/
Abstract

The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been supported by various clinical studies. However, stem cell transplantation is limited in clinical application due to its low survival rate, low liver implantation rate, and possible carcinogenicity. Recently, there has been increasing interest in the use of MSC-exos due to their widespread availability, low immunogenicity, and non-carcinogenic properties. Numerous studies have demonstrated the potential of MSC-exos in treating liver fibrosis and preventing progression to end-stage liver disease. This study aimed to systematically investigate the efficacy of MSC-exos single administration in the treatment of hepatic fibrosis and the combined advantages of MSC-exos in combination with drug therapy (MSC-exos-drugs). Data sources included PubMed, Web of Science, Embase, and the Cochrane Library, which were built up to January 2024. The population, intervention, comparison, outcomes, and study design (PICOS) principle was used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. After screening, a total of 18 papers (19 studies) were included, of which 12 involved MSC-exos single administration for the treatment of liver fibrosis and 6 involved MSC-exos-drugs for the treatment of liver fibrosis. Pooled analysis revealed that MSC-exos significantly improved liver function, promoted the repair of damaged liver tissue, and slowed the progression of hepatic fibrosis and that MSC-exos-drugs were more efficacious than MSC-exos single administration. Subgroup analyses revealed that the use of AD-MSC-exos resulted in more consistent and significant efficacy when MSC-exos was used to treat hepatic fibrosis. For MSC-exos-drugs, a more stable end result is obtained by kit extraction. Similarly, infusion through the abdominal cavity is more effective. The results suggest that MSC-exos can effectively treat liver fibrosis and that MSC-exos-drugs are more effective than MSC-exos single administration. Although the results of the subgroup analyses provide recommendations for clinical treatment, a large number of high-quality experimental validations are still needed. CRD42024516199.

摘要

间充质干细胞(MSCs)治疗肝纤维化的疗效已得到多项临床研究的支持。然而,干细胞移植因其低存活率、低肝脏植入率以及可能的致癌性,在临床应用中受到限制。近年来,由于MSC外泌体广泛可得、低免疫原性和非致癌特性,人们对其使用的兴趣日益增加。大量研究已证明MSC外泌体在治疗肝纤维化和预防进展至终末期肝病方面的潜力。本研究旨在系统地研究单次给予MSC外泌体治疗肝纤维化的疗效以及MSC外泌体与药物治疗联合使用(MSC外泌体-药物)的综合优势。数据来源包括截至2024年1月建立的PubMed、Web of Science、Embase和Cochrane图书馆。采用人群、干预措施、对照、结局指标和研究设计(PICOS)原则筛选文献,并评估文献质量以评估偏倚风险。最后,提取每项研究结局指标的数据进行合并分析。筛选后,共纳入18篇论文(19项研究),其中12项涉及单次给予MSC外泌体治疗肝纤维化,6项涉及MSC外泌体-药物治疗肝纤维化。合并分析显示,MSC外泌体显著改善肝功能,促进受损肝组织修复,减缓肝纤维化进展,且MSC外泌体-药物比单次给予MSC外泌体更有效。亚组分析显示,当使用MSC外泌体治疗肝纤维化时,使用脂肪间充质干细胞来源的外泌体(AD-MSC-exos)产生的疗效更一致且显著。对于MSC外泌体-药物,通过试剂盒提取可获得更稳定的最终结果。同样,经腹腔输注更有效。结果表明,MSC外泌体可有效治疗肝纤维化,且MSC外泌体-药物比单次给予MSC外泌体更有效。尽管亚组分析结果为临床治疗提供了建议,但仍需要大量高质量的实验验证。CRD42024516199。

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