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

TL;DR

This study reviews and analyzes how mesenchymal stem cell-derived extracellular vesicles can treat breast cancer in lab settings, showing they reduce cancer cell growth and increase cell death.

Contribution

The paper provides a systematic review and meta-analysis of in vitro studies on MSC-EVs for breast cancer, revealing consistent therapeutic effects and dormancy risks.

Findings

MSC-EVs significantly reduced cancer cell viability and migration in multiple cell lines.

Engineered MSC-EVs showed improved specificity and efficacy when loaded with therapeutic miRNAs or drugs.

Unmodified bone marrow MSC-EVs carrying miR-23b were linked to cancer dormancy in vivo.

Abstract

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 (I2 = 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.

Tamadon and colleagues present a systematic review and meta-analysis of in vitro studies evaluating the efficacy of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) therapy in breast cancer. Their findings reveal that MSC-EVs significantly reduce tumor cell viability and migration while enhancing apoptosis, highlighting both therapeutic promise and potential dormancy-associated risks for translational applications.

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