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The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis
BACKGROUND: Rheumatoid arthritis is a chronic systemic autoimmune disease that involves transformation of the lining of synovial joints into an invasive and destructive tissue. Synovial fibroblasts become transformed, invading and destroying the bone and cartilage of the affected joint(s). Due to th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601129/ https://www.ncbi.nlm.nih.gov/pubmed/37885040 http://dx.doi.org/10.1186/s13075-023-03185-6 |
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author | Bruckner, Shane Capria, Vittoria M. Zeno, Braden Leblebicioglu, Binnaz Goyal, Kanu Vasileff, William K. Awan, Hisham Willis, William L. Ganesan, Latha P. Jarjour, Wael N. |
author_facet | Bruckner, Shane Capria, Vittoria M. Zeno, Braden Leblebicioglu, Binnaz Goyal, Kanu Vasileff, William K. Awan, Hisham Willis, William L. Ganesan, Latha P. Jarjour, Wael N. |
author_sort | Bruckner, Shane |
collection | PubMed |
description | BACKGROUND: Rheumatoid arthritis is a chronic systemic autoimmune disease that involves transformation of the lining of synovial joints into an invasive and destructive tissue. Synovial fibroblasts become transformed, invading and destroying the bone and cartilage of the affected joint(s). Due to the significant role these cells play in the progression of the disease process, developing a therapeutic strategy to target and inhibit their invasive destructive nature could help patients who are afflicted with this debilitating disease. Gingival-derived mesenchymal stem cells are known to possess immunomodulatory properties and have been studied extensively as potential cell-based therapeutics for several autoimmune disorders. METHODS: A chimeric human/mouse model of synovitis was created by surgically implanting SCID mice with a piece of human articular cartilage surrounded by RASF. Mice were injected once with either GMSC or GMSCExo at 5–7 days post-implantation. Histology and IHC were used to assess RASF invasion of the cartilage. Flow cytometry was used to understand the homing ability of GMSC in vivo and the incidence of apoptosis of RASF in vitro. RESULTS: We demonstrate that both GMSC and GMSCExo are potent inhibitors of the deleterious effects of RASF. Both treatments were effective in inhibiting the invasive destructive properties of RASF as well as the potential for these cells to migrate to secondary locations and attack the cartilage. GMSC home to the site of the implant and induce programmed cell death of the RASF. CONCLUSIONS: Our results indicate that both GMSC and GMSCExo can block the pathological effects of RASF in this chimeric model of RA. A single dose of either GMSC or GMSCExo can inhibit the deleterious effects of RASF. These treatments can also block the invasive migration of the RASF, suggesting that they can inhibit the spread of RA to other joints. Because the gingival tissue is harvested with little difficulty, relatively small amounts of tissue are required to expand the cells, the simple in vitro expansion process, and the increasing technological advances in the production of therapeutic exosomes, we believe that GMSCExo are excellent candidates as a potential therapeutic for RA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03185-6. |
format | Online Article Text |
id | pubmed-10601129 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106011292023-10-27 The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis Bruckner, Shane Capria, Vittoria M. Zeno, Braden Leblebicioglu, Binnaz Goyal, Kanu Vasileff, William K. Awan, Hisham Willis, William L. Ganesan, Latha P. Jarjour, Wael N. Arthritis Res Ther Research BACKGROUND: Rheumatoid arthritis is a chronic systemic autoimmune disease that involves transformation of the lining of synovial joints into an invasive and destructive tissue. Synovial fibroblasts become transformed, invading and destroying the bone and cartilage of the affected joint(s). Due to the significant role these cells play in the progression of the disease process, developing a therapeutic strategy to target and inhibit their invasive destructive nature could help patients who are afflicted with this debilitating disease. Gingival-derived mesenchymal stem cells are known to possess immunomodulatory properties and have been studied extensively as potential cell-based therapeutics for several autoimmune disorders. METHODS: A chimeric human/mouse model of synovitis was created by surgically implanting SCID mice with a piece of human articular cartilage surrounded by RASF. Mice were injected once with either GMSC or GMSCExo at 5–7 days post-implantation. Histology and IHC were used to assess RASF invasion of the cartilage. Flow cytometry was used to understand the homing ability of GMSC in vivo and the incidence of apoptosis of RASF in vitro. RESULTS: We demonstrate that both GMSC and GMSCExo are potent inhibitors of the deleterious effects of RASF. Both treatments were effective in inhibiting the invasive destructive properties of RASF as well as the potential for these cells to migrate to secondary locations and attack the cartilage. GMSC home to the site of the implant and induce programmed cell death of the RASF. CONCLUSIONS: Our results indicate that both GMSC and GMSCExo can block the pathological effects of RASF in this chimeric model of RA. A single dose of either GMSC or GMSCExo can inhibit the deleterious effects of RASF. These treatments can also block the invasive migration of the RASF, suggesting that they can inhibit the spread of RA to other joints. Because the gingival tissue is harvested with little difficulty, relatively small amounts of tissue are required to expand the cells, the simple in vitro expansion process, and the increasing technological advances in the production of therapeutic exosomes, we believe that GMSCExo are excellent candidates as a potential therapeutic for RA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03185-6. BioMed Central 2023-10-26 2023 /pmc/articles/PMC10601129/ /pubmed/37885040 http://dx.doi.org/10.1186/s13075-023-03185-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Bruckner, Shane Capria, Vittoria M. Zeno, Braden Leblebicioglu, Binnaz Goyal, Kanu Vasileff, William K. Awan, Hisham Willis, William L. Ganesan, Latha P. Jarjour, Wael N. The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis |
title | The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis |
title_full | The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis |
title_fullStr | The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis |
title_full_unstemmed | The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis |
title_short | The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis |
title_sort | therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601129/ https://www.ncbi.nlm.nih.gov/pubmed/37885040 http://dx.doi.org/10.1186/s13075-023-03185-6 |
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