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Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage, often associated with an imbalance in M1/M2 macrophages. Elevated levels of anti-inflammatory M2 macrophages have been linked to a therapeutic response in RA. We have previously demonstrated tha...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605110/ https://www.ncbi.nlm.nih.gov/pubmed/37892183 http://dx.doi.org/10.3390/biom13101501 |
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author | Zhang, Bin Lai, Ruenn Chai Sim, Wei Kian Lim, Sai Kiang |
author_facet | Zhang, Bin Lai, Ruenn Chai Sim, Wei Kian Lim, Sai Kiang |
author_sort | Zhang, Bin |
collection | PubMed |
description | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage, often associated with an imbalance in M1/M2 macrophages. Elevated levels of anti-inflammatory M2 macrophages have been linked to a therapeutic response in RA. We have previously demonstrated that mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) promote M2 polarization and hypothesized that MSC-sEVs could alleviate RA severity with a concomitant increase in M2 polarization. Here, we treated a mouse model of collagen-induced arthritis (CIA) with MSC-sEVs. Relative to vehicle-treated CIA mice, both low (1 μg) and high (10 μg) doses of MSC-sEVs were similarly efficacious but not as efficacious as Prednisolone, the positive control. MSC-sEV treatment resulted in statistically significant reductions in disease progression rate and disease severity as measured by arthritic index (AI), anti-CII antibodies, IL-6, and C5b-9 plasma levels. There were no statistically significant differences in the treatment outcome between low (1 μg) and high (10 μg) doses of MSC-sEVs. Furthermore, immunohistochemical analysis revealed that concomitant with the therapeutic efficacy, MSC-sEV treatment increased anti-inflammatory M2 macrophages and decreased pro-inflammatory M1 macrophages in the synovium. Consistent with increased M2 macrophages, histopathological examination also revealed reduced inflammation, pannus formation, cartilage damage, bone resorption, and periosteal new bone formation in the MSC-sEV-treated group compared to the vehicle group. These findings suggest that MSC-sEVs are potential biologic disease-modifying antirheumatic drugs (DMARDs) that can help slow or halt RA joint damage and preserve joint function. |
format | Online Article Text |
id | pubmed-10605110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106051102023-10-28 Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance Zhang, Bin Lai, Ruenn Chai Sim, Wei Kian Lim, Sai Kiang Biomolecules Article Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage, often associated with an imbalance in M1/M2 macrophages. Elevated levels of anti-inflammatory M2 macrophages have been linked to a therapeutic response in RA. We have previously demonstrated that mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) promote M2 polarization and hypothesized that MSC-sEVs could alleviate RA severity with a concomitant increase in M2 polarization. Here, we treated a mouse model of collagen-induced arthritis (CIA) with MSC-sEVs. Relative to vehicle-treated CIA mice, both low (1 μg) and high (10 μg) doses of MSC-sEVs were similarly efficacious but not as efficacious as Prednisolone, the positive control. MSC-sEV treatment resulted in statistically significant reductions in disease progression rate and disease severity as measured by arthritic index (AI), anti-CII antibodies, IL-6, and C5b-9 plasma levels. There were no statistically significant differences in the treatment outcome between low (1 μg) and high (10 μg) doses of MSC-sEVs. Furthermore, immunohistochemical analysis revealed that concomitant with the therapeutic efficacy, MSC-sEV treatment increased anti-inflammatory M2 macrophages and decreased pro-inflammatory M1 macrophages in the synovium. Consistent with increased M2 macrophages, histopathological examination also revealed reduced inflammation, pannus formation, cartilage damage, bone resorption, and periosteal new bone formation in the MSC-sEV-treated group compared to the vehicle group. These findings suggest that MSC-sEVs are potential biologic disease-modifying antirheumatic drugs (DMARDs) that can help slow or halt RA joint damage and preserve joint function. MDPI 2023-10-10 /pmc/articles/PMC10605110/ /pubmed/37892183 http://dx.doi.org/10.3390/biom13101501 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Bin Lai, Ruenn Chai Sim, Wei Kian Lim, Sai Kiang Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance |
title | Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance |
title_full | Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance |
title_fullStr | Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance |
title_full_unstemmed | Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance |
title_short | Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance |
title_sort | therapeutic efficacy of mesenchymal stem/stromal cell small extracellular vesicles in alleviating arthritic progression by restoring macrophage balance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605110/ https://www.ncbi.nlm.nih.gov/pubmed/37892183 http://dx.doi.org/10.3390/biom13101501 |
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