Exosomes derived from ALR-modified adipose mesenchymal stem cells mediate hepatoprotective effects on hepatic ischemia-reperfusion injury by promoting regeneration and protecting mitochondria.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-07-15 DOI:10.1186/s13287-025-04517-w

YaJun Ma, Tao Liu, Pujun Li, Lei Cao, Xiangyu Lu, HongBin Wang

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Abstract

Background: Exosomes are rich in bioactive molecules. Their unique lipid bilayer structure gives them the advantages of protecting the contents from degradation, easy cellular uptake, and good passive targeting. MSC-derived exosomes, which are natural vesicles ideal for gene delivery, exhibit a broad spectrum of therapeutic benefits.

Methods: In this study, which combines cell-free therapy with gene therapy, adipose mesenchymal stem cells (ADSCs) were genetically modified with augmenter of liver regeneration (ALR) to derive exosomes overexpressing ALR, which were used as therapeutic agents in a miniature porcine model of laparoscopic hepatic ischemia‒reperfusion injury (IRI) combined with partial hepatectomy injury.

Results: The findings of this study demonstrated that ALR-overexpressing adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) ameliorate hepatic tissue injury, reduce apoptosis, promote hepatic regeneration, and protect the integrity of the cellular mitochondrial structure and function.

Conclusions: In conclusion, ALR gene-modified ADSC-Exo strongly attenuate liver injury and promote liver tissue repair.

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来自alr修饰的脂肪间充质干细胞的外泌体通过促进再生和保护线粒体介导肝缺血再灌注损伤的肝保护作用。

背景：外泌体富含生物活性分子。其独特的脂质双层结构使其具有保护内容物不被降解、易于细胞吸收和良好的被动靶向的优点。骨髓间质干细胞衍生的外泌体是基因传递的天然囊泡，具有广泛的治疗效果。方法：本研究采用无细胞治疗和基因治疗相结合的方法，对脂肪间充质干细胞（ADSCs）进行肝再生增强剂（ALR）的基因修饰，获得过表达ALR的外泌体，并将其作为治疗药物用于小型猪腹腔镜肝缺血再灌注损伤（IRI）合并肝部分切除术损伤模型。结果：本研究结果表明，过表达alr的脂肪间充质干细胞衍生外泌体（ADSC-Exo）可改善肝组织损伤，减少细胞凋亡，促进肝脏再生，保护细胞线粒体结构和功能的完整性。结论：ALR基因修饰的ADSC-Exo能明显减轻肝损伤，促进肝组织修复。

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 Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.