Print Email Facebook Twitter Mesenchymal stem/stromal cells-derived extracellular vesicles as a potentially more beneficial therapeutic strategy than MSC-based treatment in a mild metabolic osteoarthritis model Title Mesenchymal stem/stromal cells-derived extracellular vesicles as a potentially more beneficial therapeutic strategy than MSC-based treatment in a mild metabolic osteoarthritis model Author Warmink, Kelly (University Medical Center Utrecht; Regenerative Medicine Center Utrecht) Rios, Jaqueline L. (University Medical Center Utrecht; Regenerative Medicine Center Utrecht) Varderidou-Minasian, Suzy (University Medical Center Utrecht; Regenerative Medicine Center Utrecht) Torres-Torrillas, Marta (CEU Cardenal Herrera University) van Valkengoed, Devin R. (University Medical Center Utrecht; Regenerative Medicine Center Utrecht) Versteeg, Sabine (University Medical Center Utrecht) Eijkelkamp, Niels (University Medical Center Utrecht) Weinans, Harrie (TU Delft Biomaterials & Tissue Biomechanics; University Medical Center Utrecht; Regenerative Medicine Center Utrecht) Korthagen, Nicoline M. (University Medical Center Utrecht; Regenerative Medicine Center Utrecht) Lorenowicz, Magdalena J. (University Medical Center Utrecht; Regenerative Medicine Center Utrecht; Biomedical Primate Research Centre) Date 2023 Abstract Background: Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) hold promise as a disease modifying treatment in osteoarthritis (OA). Obesity, and its associated inflammation, contribute to OA development and metabolic OA represents a specific and significant group of the OA patient population. Given their immunomodulatory properties, MSC and MSC-EVs are especially interesting for this group of patients as a therapeutic option. Here, we were the first to compare the therapeutic efficacy of MSCs and MSC-EVs in a mild OA model taking these metabolic aspects into consideration. Methods: Male Wistar-Han rats (Crl:WI(Han) (n = 36) were fed a high fat diet for 24 weeks, with unilateral induction of OA by groove surgery after 12 weeks. Eight days after surgery rats were randomized in three treatment groups receiving MSCs, MSC-EVs or vehicle injection. Pain-associated behavior, joint degeneration, and local and systemic inflammation were measured. Results: We demonstrated that despite not having a significant therapeutic effect, MSC-EV treatment results in lower cartilage degeneration, less pain behaviour, osteophytosis and joint inflammation, than MSC treatment. Suggesting that MSC-EVs could be a more promising therapeutic strategy than MSCs in this mild metabolic OA model. Conclusion: In summary, we find that MSC treatment has negative effects on the joint in metabolic mild OA. This is an essential finding for the significant group of patients with metabolic OA phenotype, and might help to understand why clinical translation of MSC treatment shows varying therapeutic efficacy thus far. Our results also suggest that MSC-EV-based treatment might be a promising option for these patients, however MSC-EV therapeutic efficacy will need improvement. Subject Cartilage regenerationExtracellular vesiclesInflammationMesenchymal stem/stromal cellsOsteoarthritisRat high fat diet groove model To reference this document use: http://resolver.tudelft.nl/uuid:271f2893-7827-4173-b2ad-653e17b14707 DOI https://doi.org/10.1186/s13287-023-03368-7 Source Stem Cell Research and Therapy, 14 (1) Part of collection Institutional Repository Document type journal article Rights © 2023 Kelly Warmink, Jaqueline L. Rios, Suzy Varderidou-Minasian, Marta Torres-Torrillas, Devin R. van Valkengoed, Sabine Versteeg, Niels Eijkelkamp, Harrie Weinans, Nicoline M. Korthagen, Magdalena J. Lorenowicz Files PDF s13287_023_03368_7.pdf 7.87 MB Close viewer /islandora/object/uuid:271f2893-7827-4173-b2ad-653e17b14707/datastream/OBJ/view