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Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis
Rationale: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and damage to articular tissues that can lead to irreversible joint damage and progressive disability. The multipotent mesenchymal stem cells (MSCs) play an important role in immune disorders and tiss...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899585/ https://www.ncbi.nlm.nih.gov/pubmed/35265215 http://dx.doi.org/10.7150/thno.66905 |
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author | Gong, Zheli He, Yanni Zhou, Meijun Xin, Huijuan Pan, Min Fiaz, Muhammad Liu, Hongmei Yan, Fei |
author_facet | Gong, Zheli He, Yanni Zhou, Meijun Xin, Huijuan Pan, Min Fiaz, Muhammad Liu, Hongmei Yan, Fei |
author_sort | Gong, Zheli |
collection | PubMed |
description | Rationale: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and damage to articular tissues that can lead to irreversible joint damage and progressive disability. The multipotent mesenchymal stem cells (MSCs) play an important role in immune disorders and tissue regeneration. However, their immunosuppressive effects and the underlying mechanisms are largely unclear due to the lack of tools for real-time imaging of MSCs in vivo. Gas vesicles (GVs) are biosynthetic nanobubbles that are ejected from aquatic microbes, such as bacteria and archaea, and have an excellent ultrasound imaging capacity. Methods: We harvested MSCs from the bone marrow of Sprague Dawley (SD) rats. Then, GVs were synthesized and incubated with MSCs to obtain intracellularly labeled MSCs. We firstly tested the ultrasound imaging of GV@MSCs in vitro and in vivo and then explored the therapeutic effect of GV@MSCs combined with methotrexate (MTX) in RA rats. Results: These GV@MSCs showed significant contrast-enhanced ultrasound signals without a loss of viability and differentiation capacity. In addition, the GV@MSCs could be imaged in real-time for 5 days using ultrasound both in vitro and in vivo, making it possible to visually track their migration and homing to the joint cavity from the subcutaneous layer of lateral malleolus joints in the injected RA rats. Furthermore, GV@MSCs significantly enhanced the curative effect of methotrexate (MTX) against RA, resulting in decreased paw thickness, lower arthritis index score, reduced bone erosion and cartilage destruction, compared to the PBS, free MTX, and GV@MSCs groups. Conclusion: We developed a novel therapeutic strategy against RA using GVs-loaded MSCs that can be tracked in vivo in real-time. |
format | Online Article Text |
id | pubmed-8899585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-88995852022-03-08 Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis Gong, Zheli He, Yanni Zhou, Meijun Xin, Huijuan Pan, Min Fiaz, Muhammad Liu, Hongmei Yan, Fei Theranostics Research Paper Rationale: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and damage to articular tissues that can lead to irreversible joint damage and progressive disability. The multipotent mesenchymal stem cells (MSCs) play an important role in immune disorders and tissue regeneration. However, their immunosuppressive effects and the underlying mechanisms are largely unclear due to the lack of tools for real-time imaging of MSCs in vivo. Gas vesicles (GVs) are biosynthetic nanobubbles that are ejected from aquatic microbes, such as bacteria and archaea, and have an excellent ultrasound imaging capacity. Methods: We harvested MSCs from the bone marrow of Sprague Dawley (SD) rats. Then, GVs were synthesized and incubated with MSCs to obtain intracellularly labeled MSCs. We firstly tested the ultrasound imaging of GV@MSCs in vitro and in vivo and then explored the therapeutic effect of GV@MSCs combined with methotrexate (MTX) in RA rats. Results: These GV@MSCs showed significant contrast-enhanced ultrasound signals without a loss of viability and differentiation capacity. In addition, the GV@MSCs could be imaged in real-time for 5 days using ultrasound both in vitro and in vivo, making it possible to visually track their migration and homing to the joint cavity from the subcutaneous layer of lateral malleolus joints in the injected RA rats. Furthermore, GV@MSCs significantly enhanced the curative effect of methotrexate (MTX) against RA, resulting in decreased paw thickness, lower arthritis index score, reduced bone erosion and cartilage destruction, compared to the PBS, free MTX, and GV@MSCs groups. Conclusion: We developed a novel therapeutic strategy against RA using GVs-loaded MSCs that can be tracked in vivo in real-time. Ivyspring International Publisher 2022-02-21 /pmc/articles/PMC8899585/ /pubmed/35265215 http://dx.doi.org/10.7150/thno.66905 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Gong, Zheli He, Yanni Zhou, Meijun Xin, Huijuan Pan, Min Fiaz, Muhammad Liu, Hongmei Yan, Fei Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis |
title | Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis |
title_full | Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis |
title_fullStr | Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis |
title_full_unstemmed | Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis |
title_short | Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis |
title_sort | ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899585/ https://www.ncbi.nlm.nih.gov/pubmed/35265215 http://dx.doi.org/10.7150/thno.66905 |
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