Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model
Aims: Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoart...
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| Format: | Article |
| Language: | English |
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The British Editorial Society of Bone & Joint Surgery
2023-10-01
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| Series: | Bone & Joint Research |
| Subjects: | |
| Online Access: | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1210.BJR-2023-0109.R1 |
| _version_ | 1797635663225421824 |
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| author | Maria A. Forteza-Genestra Miquel Antich-Rosselló Guillem Ramis-Munar Javier Calvo Antoni Gayà Marta Monjo Joana M. Ramis |
| author_facet | Maria A. Forteza-Genestra Miquel Antich-Rosselló Guillem Ramis-Munar Javier Calvo Antoni Gayà Marta Monjo Joana M. Ramis |
| author_sort | Maria A. Forteza-Genestra |
| collection | DOAJ |
| description | Aims: Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods: pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results: Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion: In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676. |
| first_indexed | 2024-03-11T12:24:33Z |
| format | Article |
| id | doaj.art-4367898af30d4f92b0e4e76754b0dec3 |
| institution | Directory Open Access Journal |
| issn | 2046-3758 |
| language | English |
| last_indexed | 2024-03-11T12:24:33Z |
| publishDate | 2023-10-01 |
| publisher | The British Editorial Society of Bone & Joint Surgery |
| record_format | Article |
| series | Bone & Joint Research |
| spelling | doaj.art-4367898af30d4f92b0e4e76754b0dec32023-11-06T12:30:11ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582023-10-01121066767610.1302/2046-3758.1210.BJR-2023-0109.R1Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis modelMaria A. Forteza-Genestra0Miquel Antich-Rosselló1https://orcid.org/0000-0003-3784-4170Guillem Ramis-Munar2https://orcid.org/0000-0003-0588-053XJavier Calvo3https://orcid.org/0000-0002-1732-9449Antoni Gayà4https://orcid.org/0000-0002-2200-5801Marta Monjo5https://orcid.org/0000-0002-2731-9527Joana M. Ramis6https://orcid.org/0000-0001-9109-8362Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Palma, SpainMicroscopy Area, Serveis Cietificotècnics, University of the Balearic Islands, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Palma, SpainAims: Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods: pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results: Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion: In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1210.BJR-2023-0109.R1platelet lysateosteoarthritisextracellular vesiclesregenerative medicinecartilage repairhuman umbilical cord mesenchymal stromal cellsmesenchymal stromal cellsextracellular vesiclesosteoarthritis (oa)cartilageplateletsglycosaminoglycans (gag)collagensmscsdnaregenerative medicine |
| spellingShingle | Maria A. Forteza-Genestra Miquel Antich-Rosselló Guillem Ramis-Munar Javier Calvo Antoni Gayà Marta Monjo Joana M. Ramis Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model Bone & Joint Research platelet lysate osteoarthritis extracellular vesicles regenerative medicine cartilage repair human umbilical cord mesenchymal stromal cells mesenchymal stromal cells extracellular vesicles osteoarthritis (oa) cartilage platelets glycosaminoglycans (gag) collagens mscs dna regenerative medicine |
| title | Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model |
| title_full | Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model |
| title_fullStr | Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model |
| title_full_unstemmed | Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model |
| title_short | Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model |
| title_sort | comparative effect of platelet and mesenchymal stromal cell derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model |
| topic | platelet lysate osteoarthritis extracellular vesicles regenerative medicine cartilage repair human umbilical cord mesenchymal stromal cells mesenchymal stromal cells extracellular vesicles osteoarthritis (oa) cartilage platelets glycosaminoglycans (gag) collagens mscs dna regenerative medicine |
| url | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1210.BJR-2023-0109.R1 |
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