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间充质干细胞来源细胞外囊泡治疗乳腺癌:体外研究的系统综述与荟萃分析

英文原题:Mesenchymal stem cell-derived extracellular vesicle therapy in breast cancer: A systematic review and meta-analysis of in vitro studies.

PubMed 2025/12/09(内容时间) Mol Ther Oncol Q1 · IF 8.5(JCR 2025)

研究概要

在主要细胞系(MCF-7、MDA-MB-231 和 4T1)和 MSC 来源(骨髓、脂肪和脐带)中,效应保持一致,尽管存在中度异质性(I 2 = 50%-70%)。

中文摘要

间充质干/基质细胞来源细胞外囊泡(MSC-EV)因具有天然肿瘤趋向性及分子递送能力,已成为乳腺癌有前景的无细胞疗法。本系统综述和荟萃分析评估了MSC-EV的体外治疗潜力与安全性。全面检索截至2025年7月的文献,共纳入58项研究。定量提取细胞活力、凋亡和迁移数据,以及EV来源、载荷和工程策略。随机效应荟萃分析显示,MSC-EV治疗显著降低癌细胞活力(标准化均数差[SMD]=-4.79)、抑制迁移(SMD=-4.70)并增加凋亡(SMD=+4.16)。尽管存在中度异质性(I²=50%–70%),在主要细胞系(MCF-7、MDA-MB-231和4T1)及MSC来源(骨髓、脂肪和脐带)中结果一致。值得注意的是,携带miR-23b的未修饰骨髓MSC-EV与体内诱导肿瘤休眠相关;而装载治疗性miRNA或药物并经靶向配体修饰的工程化EV显示出更高特异性和疗效。MSC-EV精准工程化可增强抗肿瘤活性,但需严格控制载荷以避免休眠风险。本研究仅对体外数据进行定量分析,体内发现则用于机制背景讨论,为未来转化研究提供方法学基础。

展开英文摘要原文

Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutics for breast cancer due to their innate tumor tropism and molecular delivery capacity. This systematic review and meta-analysis evaluated the in vitro therapeutic potential and safety of MSC-EVs. A comprehensive search up to July 2025 identified 58 eligible studies. Quantitative data were extracted on cell viability, apoptosis, and migration, along with EV source, cargo, and engineering strategy. Random-effects meta-analyses showed that MSC-EV treatment significantly reduced cancer cell viability (standardized mean difference [SMD] = -4.79), inhibited migration (SMD = -4.70), and increased apoptosis (SMD = +4.16). Effects were consistent across major cell lines (MCF-7, MDA-MB-231, and 4T1) and MSC sources (bone marrow, adipose, and umbilical cord), despite moderate heterogeneity (I 2 = 50%-70%). Notably, unmodified bone marrow MSC-EVs carrying miR-23b were associated with dormancy induction in vivo , whereas engineered EVs loaded with therapeutic miRNAs or drugs and modified with targeting ligands demonstrated improved specificity and efficacy. Precision engineering of MSC-EVs can enhance antitumor activity but requires stringent cargo control to avoid dormancy risks. Only in vitro data were quantitatively analyzed, while in vivo findings were discussed for mechanistic context, providing a methodological foundation for future translational research.

论文信息

作者
Mussin NM、Zhilisbayeva KR、Baspakova A、Ishimova LA、Kurmanalina MA、Tamadon A
第一作者单位
Department of General Surgery No. 2, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
通讯作者单位
Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
文献类型
综述
期刊
Molecular therapy. Oncology2026 Mar 19
原文标识
PubMed 41510212 · DOI 10.1016/j.omton.2025.201107