Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations

Abstract Background Articular cartilage injuries can lead to pain, stiffness, and reduced mobility, and may eventually progress to osteoarthritis (OA). Despite substantial research efforts, effective therapies capable of regenerating cartilage are still lacking. Mesenchymal stromal cells (MSCs) are...

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Main Authors: María Piñeiro-Ramil, Iván Gómez-Seoane, Ana Isabel Rodríguez-Cendal, Isaac Fuentes-Boquete, Silvia Díaz-Prado
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04135-6
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author María Piñeiro-Ramil
Iván Gómez-Seoane
Ana Isabel Rodríguez-Cendal
Isaac Fuentes-Boquete
Silvia Díaz-Prado
author_facet María Piñeiro-Ramil
Iván Gómez-Seoane
Ana Isabel Rodríguez-Cendal
Isaac Fuentes-Boquete
Silvia Díaz-Prado
author_sort María Piñeiro-Ramil
collection DOAJ
description Abstract Background Articular cartilage injuries can lead to pain, stiffness, and reduced mobility, and may eventually progress to osteoarthritis (OA). Despite substantial research efforts, effective therapies capable of regenerating cartilage are still lacking. Mesenchymal stromal cells (MSCs) are known for their differentiation and immunomodulatory capabilities, yet challenges such as limited survival post-injection and inconsistent therapeutic outcomes hinder their clinical application. Recent evidence suggests that the beneficial effects of MSCs are largely mediated by their secreted small extracellular vesicles (sEVs), which have been shown to promote tissue repair and reduce inflammation. MSC-derived sEVs have shown promise in mitigating cartilage degradation and chondrocyte apoptosis, positioning them as a promising alternative to MSC-based therapies for OA treatment. This review explores the potential and limitations of MSC-derived sEVs in cartilage regeneration. Main text This systematic review was conducted following PRISMA guidelines, with a comprehensive search of the Web of Science and Scopus databases for studies published between 2019 and 2024. A total of 223 records were identified, of which 132 articles were assessed for eligibility based on general selection criteria. After full-text screening, 60 articles were initially selected, comprising 58 in vitro studies and 40 in vivo studies. Following further exclusion based on specific criteria, 33 in vitro and 28 in vivo studies from a total of 47 scientific papers were included in the final qualitative synthesis. Most studies indicate that MSC-derived sEVs enhance chondrocyte proliferation, improve cartilage extracellular matrix composition, and reduce matrix-degrading enzymes and inflammation, thereby delaying OA progression. Conclusion A growing body of evidence supports the use of MSC-derived sEVs as a therapeutic tool for preventing OA progression, with most studies reporting beneficial effects on cartilage structure and function. However, challenges remain in optimizing and standardizing sEVs isolation, dosage, and delivery methods for clinical application. Further research is necessary to elucidate the mechanisms underlying sEVs-mediated cartilage regeneration and to facilitate their translation into effective OA therapies.
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spelling doaj-art-029ec7e68a7b40288b7fbe15537070512025-01-26T12:18:10ZengBMCStem Cell Research & Therapy1757-65122025-01-0116112010.1186/s13287-025-04135-6Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitationsMaría Piñeiro-Ramil0Iván Gómez-Seoane1Ana Isabel Rodríguez-Cendal2Isaac Fuentes-Boquete3Silvia Díaz-Prado4Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Pública Gallega de Investigación Biomédica INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS)Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Pública Gallega de Investigación Biomédica INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS)Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Pública Gallega de Investigación Biomédica INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS)Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Pública Gallega de Investigación Biomédica INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS)Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Pública Gallega de Investigación Biomédica INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS)Abstract Background Articular cartilage injuries can lead to pain, stiffness, and reduced mobility, and may eventually progress to osteoarthritis (OA). Despite substantial research efforts, effective therapies capable of regenerating cartilage are still lacking. Mesenchymal stromal cells (MSCs) are known for their differentiation and immunomodulatory capabilities, yet challenges such as limited survival post-injection and inconsistent therapeutic outcomes hinder their clinical application. Recent evidence suggests that the beneficial effects of MSCs are largely mediated by their secreted small extracellular vesicles (sEVs), which have been shown to promote tissue repair and reduce inflammation. MSC-derived sEVs have shown promise in mitigating cartilage degradation and chondrocyte apoptosis, positioning them as a promising alternative to MSC-based therapies for OA treatment. This review explores the potential and limitations of MSC-derived sEVs in cartilage regeneration. Main text This systematic review was conducted following PRISMA guidelines, with a comprehensive search of the Web of Science and Scopus databases for studies published between 2019 and 2024. A total of 223 records were identified, of which 132 articles were assessed for eligibility based on general selection criteria. After full-text screening, 60 articles were initially selected, comprising 58 in vitro studies and 40 in vivo studies. Following further exclusion based on specific criteria, 33 in vitro and 28 in vivo studies from a total of 47 scientific papers were included in the final qualitative synthesis. Most studies indicate that MSC-derived sEVs enhance chondrocyte proliferation, improve cartilage extracellular matrix composition, and reduce matrix-degrading enzymes and inflammation, thereby delaying OA progression. Conclusion A growing body of evidence supports the use of MSC-derived sEVs as a therapeutic tool for preventing OA progression, with most studies reporting beneficial effects on cartilage structure and function. However, challenges remain in optimizing and standardizing sEVs isolation, dosage, and delivery methods for clinical application. Further research is necessary to elucidate the mechanisms underlying sEVs-mediated cartilage regeneration and to facilitate their translation into effective OA therapies.https://doi.org/10.1186/s13287-025-04135-6OAExosomesChondrocytesCell-free therapy
spellingShingle María Piñeiro-Ramil
Iván Gómez-Seoane
Ana Isabel Rodríguez-Cendal
Isaac Fuentes-Boquete
Silvia Díaz-Prado
Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations
Stem Cell Research & Therapy
OA
Exosomes
Chondrocytes
Cell-free therapy
title Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations
title_full Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations
title_fullStr Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations
title_full_unstemmed Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations
title_short Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations
title_sort mesenchymal stromal cells derived extracellular vesicles in cartilage regeneration potential and limitations
topic OA
Exosomes
Chondrocytes
Cell-free therapy
url https://doi.org/10.1186/s13287-025-04135-6
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