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REVIEW article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 |
doi: 10.3389/fphar.2025.1509418
This article is part of the Research Topic Extracellular Vesicles in Disease Therapy: Harnessing Diverse Origins for Advanced Treatments View all 4 articles
OPTIMIZING THERAPEUTIC OUTCOMES: PRECONDITIONING STRATEGIES FOR MSC-DERIVED EXTRACELLULAR VESICLES
Provisionally accepted- 1 Shandong Second Medical University, Weifang, China
- 2 Hamilton College New York, Clinton, New York, United States
- 3 Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) are increasingly recognized for their therapeutic potential in regenerative medicine, driven by their capabilities in immunomodulation and tissue repair. However, MSCs present risks such as immunogenic responses, malignant transformation, and the potential to transmit infectious pathogens due to their intrinsic proliferative and differentiative abilities. In contrast, MSC-EVs, particularly exosomes (MSC-exosomes, 30-150 nm in diameter), offer a safer therapeutic profile. These acellular vesicles mitigate risks associated with immune rejection and tumorigenesis and are inherently incapable of forming ectopic tissues, thereby enhancing their clinical safety and applicability. This review highlights the therapeutic promise of MSC-exosomes especially focusing on the modulation of miRNA (one of bioactive molecules in MSC-EVs) profiles through various preconditioning strategies such as exposure to hypoxia, chemotherapeutic agents, inflammatory cytokines, and physical stimuli. Such conditioning is shown to optimize their therapeutic potential. Key miRNAs including miR-21, miR-146, miR-125a, miR-126, and miR-181a are particularly noted for their roles in facilitating tissue repair and modulating inflammatory responses. These functionalities position MSC-exosomes as a valuable tool in personalized medicine, particularly in the case of exosome-based interventions. Despite the potential of MSC-EVs, this review also acknowledged the limitations of traditional MSC therapies and advocates for a strategic pivot towards exosome-based modalities to enhance therapeutic outcomes. By discussing recent advances in detail and identifying remaining pitfalls, this review aims to guide future directions in improving the efficacy of MSC-exosome-based therapeutics. Additionally, miRNA variability in MSC-EVs presents challenges due to the diverse roles of miRNAs play in regulating gene expression and cell behavior. The miRNA content of MSC-EVs can be influenced by preconditioning strategies and differences in isolation and purification methods, which 3 may alter the expression profiles of specific miRNAs, contributing to differences in their therapeutic effects.
Keywords: miRNA, MSC-EVs, Exosomes, Preconditioning strategies, MSCs (mesenchymal stem cells)
Received: 10 Oct 2024; Accepted: 23 Jan 2025.
Copyright: © 2025 Song, Tian, Liang, Rayhill, Ye and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Weikun Tian, Shandong Second Medical University, Weifang, China
Fengrui Liang, Shandong Second Medical University, Weifang, China
Erin Rayhill, Hamilton College New York, Clinton, 13323, New York, United States
Liping Ye, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
Xinghan Tian, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
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