The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are revolutionizing the field of regenerative medicine, becoming the core carriers of next-generation acellular therapeutic strategies. In contrast to traditional mesenchymal stem cell therapy, these nanoscale “regenerative tiny giants”...

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Main Authors: Tianhe Zhang, Liang Zhang, Xiaoxue Ma, Wenliang Song
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1612589/full
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author Tianhe Zhang
Liang Zhang
Xiaoxue Ma
Wenliang Song
author_facet Tianhe Zhang
Liang Zhang
Xiaoxue Ma
Wenliang Song
author_sort Tianhe Zhang
collection DOAJ
description Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are revolutionizing the field of regenerative medicine, becoming the core carriers of next-generation acellular therapeutic strategies. In contrast to traditional mesenchymal stem cell therapy, these nanoscale “regenerative tiny giants” offer significant advantages, including low immunogenicity, efficient biological barrier penetration, and stable storage. As natural bioactive molecular carriers, MSC-EVs precisely regulate the inflammatory response, angiogenesis, and tissue repair processes in target tissues by delivering functional RNA, proteins, and other signaling elements. They have demonstrated multidimensional therapeutic potential in diseases such as bone and joint regeneration, nerve function reconstruction, myocardial repair, and skin wound healing. Worldwide, 64 registered clinical trials have preliminarily validated the safety and applicability of MSC-EVs across various diseases. Notably, they have shown significant progress in treating severe coronavirus disease 2019 (COVID-19), ischemic stroke, and complex wound healing. However, the lack of standardization in production processes, insufficient targeting for in vivo delivery, and the scarcity of long-term biodistribution data remain core bottlenecks limiting the clinical translation of MSC-EVs. Future interdisciplinary technologies, including 3-dimensional (3D) dynamic culture, genetic engineering, and intelligent slow-release systems, are expected to facilitate the transition of MSC-EVs from the lab to large-scale applications. This shift may transform “injectable regenerative factors” into “programmable nanomedicines”, offering new solutions for precision medicine.
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spelling doaj-art-ae229cd6470f4563bf04ab52353d00a82025-08-20T02:40:07ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-07-011310.3389/fcell.2025.16125891612589The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeuticsTianhe Zhang0Liang Zhang1Xiaoxue Ma2Wenliang Song3Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Neonatology, The Frist Hospital of China Medical University, Shenyang, ChinaDepartment of Pediatrics, The Frist Hospital of China Medical University, Shenyang, ChinaDepartment of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, ChinaMesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are revolutionizing the field of regenerative medicine, becoming the core carriers of next-generation acellular therapeutic strategies. In contrast to traditional mesenchymal stem cell therapy, these nanoscale “regenerative tiny giants” offer significant advantages, including low immunogenicity, efficient biological barrier penetration, and stable storage. As natural bioactive molecular carriers, MSC-EVs precisely regulate the inflammatory response, angiogenesis, and tissue repair processes in target tissues by delivering functional RNA, proteins, and other signaling elements. They have demonstrated multidimensional therapeutic potential in diseases such as bone and joint regeneration, nerve function reconstruction, myocardial repair, and skin wound healing. Worldwide, 64 registered clinical trials have preliminarily validated the safety and applicability of MSC-EVs across various diseases. Notably, they have shown significant progress in treating severe coronavirus disease 2019 (COVID-19), ischemic stroke, and complex wound healing. However, the lack of standardization in production processes, insufficient targeting for in vivo delivery, and the scarcity of long-term biodistribution data remain core bottlenecks limiting the clinical translation of MSC-EVs. Future interdisciplinary technologies, including 3-dimensional (3D) dynamic culture, genetic engineering, and intelligent slow-release systems, are expected to facilitate the transition of MSC-EVs from the lab to large-scale applications. This shift may transform “injectable regenerative factors” into “programmable nanomedicines”, offering new solutions for precision medicine.https://www.frontiersin.org/articles/10.3389/fcell.2025.1612589/fullextracellular vesiclesmesenchymal stem cellsexosomestherapybioengineeringanimals
spellingShingle Tianhe Zhang
Liang Zhang
Xiaoxue Ma
Wenliang Song
The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics
Frontiers in Cell and Developmental Biology
extracellular vesicles
mesenchymal stem cells
exosomes
therapy
bioengineering
animals
title The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics
title_full The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics
title_fullStr The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics
title_full_unstemmed The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics
title_short The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics
title_sort tiny giants of regeneration msc derived extracellular vesicles as next generation therapeutics
topic extracellular vesicles
mesenchymal stem cells
exosomes
therapy
bioengineering
animals
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1612589/full
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