Therapeutic potential of MSCs and their exosomes in hepatic Ischaemia-Reperfusion injury: a systematic review and meta-analysis of rodent studies.

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cells Translational Medicine Pub Date : 2026-01-26 DOI:10.1093/stcltm/szaf078

Yanxi Mu, Weixiong Zhu, Wentao Ma, Yu Cheng, Bo Ren, Yusheng Cheng, Wence Zhou

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引用次数: 0

Abstract

Objective: This meta-analysis comprehensively evaluates the therapeutic efficacy and mechanisms of mesenchymal stem cells (MSCs) and their exosomes in rodent models of hepatic ischemia-reperfusion injury (HIRI), providing preclinical support for future clinical translation.

Methods: In accordance with the PRISMA guidelines, we systematically searched PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov for studies published from inception to January 13, 2025, and identified 64 eligible studies. Risk of bias was evaluated using the SYRCLE tool, and Review Manager 5.4.1 was employed for meta-analysis, calculating SMD and 95%CI. Primary outcomes included liver function (ALT/AST), histopathological scores (Suzuki's score, necrotic area ratio), inflammatory cytokines (TNF-α), and apoptosis markers (c-caspase 3).

Results: MSCs and their exosomes significantly ameliorated HIRI. In the 60-minute ischemia group, ALT (SMD = 3.49, P < .00001) and AST (SMD = 3.86, P < .00001) decreased, along with lower Suzuki scores (SMD = 3.12), necrotic area ratios (SMD = 3.56), and TNF-α levels (SMD = 2.83). In the 90-minute group, ALT (SMD = 4.09, P < .00001) and AST (SMD = 3.78, P < .00001) were also reduced. Mechanistically, MSCs exert therapeutic effects through antioxidative, anti-inflammatory, anti-apoptotic, and pro-regenerative pathways. Considerable heterogeneity (I2 = 52-86%) was observed, likely due to variations in dosage (1 × 105-1 × 109 cells), administration routes (intravenous/portal vein), and reperfusion durations (3-24 hours). Genetic modifications (e.g., HO-1 overexpression) further enhanced therapeutic outcomes.

Conclusion: MSCs and their exosomes mitigate HIRI through multi-target mechanisms but requires standardized protocols. Future studies should prioritize large-animal validation and translational research to facilitate precision clinical application.

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间充质干细胞及其外泌体在肝缺血再灌注损伤中的治疗潜力：对啮齿动物研究的系统回顾和荟萃分析。

目的：本荟萃分析综合评价间充质干细胞（MSCs）及其外泌体在啮齿动物肝缺血再灌注损伤（HIRI）模型中的治疗效果和机制，为未来的临床转化提供临床前支持。方法：根据PRISMA指南，我们系统地检索PubMed、Web of Science、Embase、Cochrane Library和ClinicalTrials.gov从成立到2025年1月13日发表的研究，并确定64项符合条件的研究。使用sycle工具评估偏倚风险，采用Review Manager 5.4.1进行meta分析，计算SMD和95%CI。主要结局包括肝功能（ALT/AST）、组织病理学评分（铃木评分、坏死面积比）、炎症因子（TNF-α）和凋亡标志物（c-caspase 3）。结果：间充质干细胞及其外泌体可显著改善HIRI。缺血60分钟组ALT （SMD = 3.49, P < 0.00001）、AST （SMD = 3.86, P < 0.00001）降低，Suzuki评分（SMD = 3.12）、坏死面积比（SMD = 3.56）、TNF-α水平（SMD = 2.83）降低。在90分钟组，ALT （SMD = 4.09, P < 0.00001）和AST （SMD = 3.78, P < 0.00001）也降低。从机制上讲，MSCs通过抗氧化、抗炎、抗凋亡和促再生途径发挥治疗作用。观察到相当大的异质性（I2 = 52-86%），可能是由于剂量（1 × 105-1 × 109细胞）、给药途径（静脉/门静脉）和再灌注持续时间（3-24小时）的变化。基因修饰（如HO-1过表达）进一步提高了治疗效果。结论：间质干细胞及其外泌体通过多靶点机制减轻HIRI，但需要标准化的方案。未来的研究应优先考虑大动物验证和转化研究，以促进精准临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-

CiteScore

12.90

自引率

3.30%

发文量

140

审稿时长

6-12 weeks

期刊介绍： STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.