Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model

Objective: MSCs and Platelet-Rich Plasma are the main focus in the study of new regenerative treatments aimed to reverse Osteoarthritis (OA). However, extracellular vesicles (EVs) present several advantages to cell-based treatments. Thus, the aim of this study was to compare and evaluate the regener...

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Main Authors: Maria Antònia Forteza-Genestra, Miquel Antich-Rosselló, Carmen Ráez-Meseguer, Anna Tomàs Sangenís, Javier Calvo, Antoni Gayà, Marta Monjo, Joana Maria Ramis
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Journal of Orthopaedic Translation
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214031X23000797
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author Maria Antònia Forteza-Genestra
Miquel Antich-Rosselló
Carmen Ráez-Meseguer
Anna Tomàs Sangenís
Javier Calvo
Antoni Gayà
Marta Monjo
Joana Maria Ramis
author_facet Maria Antònia Forteza-Genestra
Miquel Antich-Rosselló
Carmen Ráez-Meseguer
Anna Tomàs Sangenís
Javier Calvo
Antoni Gayà
Marta Monjo
Joana Maria Ramis
author_sort Maria Antònia Forteza-Genestra
collection DOAJ
description Objective: MSCs and Platelet-Rich Plasma are the main focus in the study of new regenerative treatments aimed to reverse Osteoarthritis (OA). However, extracellular vesicles (EVs) present several advantages to cell-based treatments. Thus, the aim of this study was to compare and evaluate the regenerative potential of MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in an OA cartilage rat model. Design: OA in vivo model was established through injection of 6 mg MIA in the rat knee joints. After 14 and 21 days, OA knee joints were treated with 1 × 1010 particles of pEVs or cEVs. At day 28, the animals were sacrificed, plasma was collected to quantify CTX-II and knee joints were excised to be evaluated by Cone Beam Computed Tomography (CBCT). After decalcification, histology was used to determine the OARSI score and to visualize collagen and glycosaminoglycan content. Results: pEVs and cEVs samples did not show significant differences per se but they did in terms of regenerative effects on OA knee joints. pEVs-treated knee joints showed better subchondral bone integrity in CT-analysed parameters when compared to cEVs or OA group, showing similar values to the healthy control group. Moreover, OARSI score indicated that pEVs showed a greater OA reversion in knee joints, especially in female rats, and so indicated the analysed histological images. Conclusions: pEVs are proposed as a viable regeneration treatment for OA since they are not only capable of exerting their regenerative potential on osteoarthritic cartilage, but also outperform cEVs in terms of efficacy, particularly in females. Significance statement: Osteoarthritis (OA) is one of the most age-related diseases. It is estimated that 500 million people suffer from OA worldwide, representing the principal cause of chronic disability in adults. In the present study we evaluated the therapeutic effect of extracellular vesicles (EVs) from different sources (platelet lysate and human umbilical cord mesenchymal stromal cells) in an in vivo rat model. Our results demonstrate that platelet-derived EVs (pEVs) induce an OA reversion in knee joints, thus evidencing the therapeutic potential of pEVs as cell-free regenerative agents for OA treatment. The translational potential of this article: Platelet-derived extracellular vesicles (pEVs) offer a promising cell-free therapy option for OA treatment. Their production could be easily standardized and reproduced without extensive platelet harvesting and amplification, thus paving the way for their clinical translation.
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spelling doaj.art-0ff182ddb5d146228b541a5ea7fad13c2024-04-18T04:20:24ZengElsevierJournal of Orthopaedic Translation2214-031X2024-03-014519Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat modelMaria Antònia Forteza-Genestra0Miquel Antich-Rosselló1Carmen Ráez-Meseguer2Anna Tomàs Sangenís3Javier Calvo4Antoni Gayà5Marta Monjo6Joana Maria Ramis7Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain; Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain; Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain; Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07120, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain; Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain; Fundació Banc de Sang i Teixits de les Illes Balears (FBSTIB), 07004, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain; Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain; Fundació Banc de Sang i Teixits de les Illes Balears (FBSTIB), 07004, Palma, SpainCell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain; Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain; Departament de Biologia Fonamental i Ciències de la Salut, UIB, Palma, Spain; Corresponding author. Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122 Palma, Spain.Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain; Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain; Departament de Biologia Fonamental i Ciències de la Salut, UIB, Palma, Spain; Corresponding author. Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Crta Valldemossa km 7.5, 07122, Palma, Spain.Objective: MSCs and Platelet-Rich Plasma are the main focus in the study of new regenerative treatments aimed to reverse Osteoarthritis (OA). However, extracellular vesicles (EVs) present several advantages to cell-based treatments. Thus, the aim of this study was to compare and evaluate the regenerative potential of MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in an OA cartilage rat model. Design: OA in vivo model was established through injection of 6 mg MIA in the rat knee joints. After 14 and 21 days, OA knee joints were treated with 1 × 1010 particles of pEVs or cEVs. At day 28, the animals were sacrificed, plasma was collected to quantify CTX-II and knee joints were excised to be evaluated by Cone Beam Computed Tomography (CBCT). After decalcification, histology was used to determine the OARSI score and to visualize collagen and glycosaminoglycan content. Results: pEVs and cEVs samples did not show significant differences per se but they did in terms of regenerative effects on OA knee joints. pEVs-treated knee joints showed better subchondral bone integrity in CT-analysed parameters when compared to cEVs or OA group, showing similar values to the healthy control group. Moreover, OARSI score indicated that pEVs showed a greater OA reversion in knee joints, especially in female rats, and so indicated the analysed histological images. Conclusions: pEVs are proposed as a viable regeneration treatment for OA since they are not only capable of exerting their regenerative potential on osteoarthritic cartilage, but also outperform cEVs in terms of efficacy, particularly in females. Significance statement: Osteoarthritis (OA) is one of the most age-related diseases. It is estimated that 500 million people suffer from OA worldwide, representing the principal cause of chronic disability in adults. In the present study we evaluated the therapeutic effect of extracellular vesicles (EVs) from different sources (platelet lysate and human umbilical cord mesenchymal stromal cells) in an in vivo rat model. Our results demonstrate that platelet-derived EVs (pEVs) induce an OA reversion in knee joints, thus evidencing the therapeutic potential of pEVs as cell-free regenerative agents for OA treatment. The translational potential of this article: Platelet-derived extracellular vesicles (pEVs) offer a promising cell-free therapy option for OA treatment. Their production could be easily standardized and reproduced without extensive platelet harvesting and amplification, thus paving the way for their clinical translation.http://www.sciencedirect.com/science/article/pii/S2214031X23000797Extracellular vesiclesKnee OA in vivo modelMesenchymal stromal cellsOsteoarthritisPlatelet lysate
spellingShingle Maria Antònia Forteza-Genestra
Miquel Antich-Rosselló
Carmen Ráez-Meseguer
Anna Tomàs Sangenís
Javier Calvo
Antoni Gayà
Marta Monjo
Joana Maria Ramis
Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model
Journal of Orthopaedic Translation
Extracellular vesicles
Knee OA in vivo model
Mesenchymal stromal cells
Osteoarthritis
Platelet lysate
title Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model
title_full Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model
title_fullStr Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model
title_full_unstemmed Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model
title_short Intra-articular injection of platelet lysate-derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model
title_sort intra articular injection of platelet lysate derived extracellular vesicles recovers from knee osteoarthritis in an in vivo rat model
topic Extracellular vesicles
Knee OA in vivo model
Mesenchymal stromal cells
Osteoarthritis
Platelet lysate
url http://www.sciencedirect.com/science/article/pii/S2214031X23000797
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