Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects
Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We desi...
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KeAi Communications Co., Ltd.
2025-03-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24005255 |
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| author | Gianluca Fontana Brett Nemke Yan Lu Connie Chamberlain Jae-Sung Lee Joshua A. Choe Hongli Jiao Michael Nelson Margot Amitrano Wan-Ju Li Mark Markel William L. Murphy |
| author_facet | Gianluca Fontana Brett Nemke Yan Lu Connie Chamberlain Jae-Sung Lee Joshua A. Choe Hongli Jiao Michael Nelson Margot Amitrano Wan-Ju Li Mark Markel William L. Murphy |
| author_sort | Gianluca Fontana |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair. We used mineral-coated microparticles to deliver TGF-β1 mRNA to autologous BMAC. mRNA-activated BMAC was suspended in peripheral blood to generate therapeutic BMAC clots, which were then implanted in rabbit osteochondral defects. Tracking studies revealed that the clots were reliably maintained in the defects for at least 2 weeks. TGF-β1 mRNA delivery significantly increased TGF-β1 production in BMAC clots and increased early expression of articular chondrocyte markers within osteochondral defects. At 9 weeks post-surgery, the mRNA-treated defects had a superior macroscopic cartilage appearance, decreased type I collagen deposition, increased stain intensity for type II collagen and increased glycosaminoglycan deposition area when compared to the controls. Despite the transient expression of therapeutic mRNA we have detected lasting effects, such as a decrease in fibrocartilage formation demonstrated by the decrease in type I collagen deposition and the improvement in macroscopic appearance in the treatment group. |
| format | Article |
| id | doaj-art-64e47237b2c745f0a1047ed1bb029f3a |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-64e47237b2c745f0a1047ed1bb029f3a2025-01-26T05:04:26ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-03-0145509519Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defectsGianluca Fontana0Brett Nemke1Yan Lu2Connie Chamberlain3Jae-Sung Lee4Joshua A. Choe5Hongli Jiao6Michael Nelson7Margot Amitrano8Wan-Ju Li9Mark Markel10William L. Murphy11Department of Orthopedics and Rehabilitation, USASchool of Veterinary Medicine, USASchool of Veterinary Medicine, USADepartment of Orthopedics and Rehabilitation, USADepartment of Orthopedics and Rehabilitation, USADepartment of Orthopedics and Rehabilitation, USADepartment of Orthopedics and Rehabilitation, USADepartment of Orthopedics and Rehabilitation, USADepartment of Orthopedics and Rehabilitation, USADepartment of Orthopedics and Rehabilitation, USASchool of Veterinary Medicine, USADepartment of Orthopedics and Rehabilitation, USA; Department of Biomedical Engineering, USA; Material Sciences and Engineering, University of Wisconsin-Madison, Madison, WI, USA; Corresponding author. Department of Orthopedics and Rehabilitation, USA.Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair. We used mineral-coated microparticles to deliver TGF-β1 mRNA to autologous BMAC. mRNA-activated BMAC was suspended in peripheral blood to generate therapeutic BMAC clots, which were then implanted in rabbit osteochondral defects. Tracking studies revealed that the clots were reliably maintained in the defects for at least 2 weeks. TGF-β1 mRNA delivery significantly increased TGF-β1 production in BMAC clots and increased early expression of articular chondrocyte markers within osteochondral defects. At 9 weeks post-surgery, the mRNA-treated defects had a superior macroscopic cartilage appearance, decreased type I collagen deposition, increased stain intensity for type II collagen and increased glycosaminoglycan deposition area when compared to the controls. Despite the transient expression of therapeutic mRNA we have detected lasting effects, such as a decrease in fibrocartilage formation demonstrated by the decrease in type I collagen deposition and the improvement in macroscopic appearance in the treatment group.http://www.sciencedirect.com/science/article/pii/S2452199X24005255CartilageFibrocartilagemRNA deliveryGene therapyMicroparticles |
| spellingShingle | Gianluca Fontana Brett Nemke Yan Lu Connie Chamberlain Jae-Sung Lee Joshua A. Choe Hongli Jiao Michael Nelson Margot Amitrano Wan-Ju Li Mark Markel William L. Murphy Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects Bioactive Materials Cartilage Fibrocartilage mRNA delivery Gene therapy Microparticles |
| title | Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects |
| title_full | Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects |
| title_fullStr | Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects |
| title_full_unstemmed | Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects |
| title_short | Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects |
| title_sort | local delivery of tgf β1 mrna decreases fibrosis in osteochondral defects |
| topic | Cartilage Fibrocartilage mRNA delivery Gene therapy Microparticles |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24005255 |
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