Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skeletal muscle cells
| Autor: | Kim M. Huffman, Catherine E. Oliver, Hailee Patel, James Hong, Jonathan R. Carter, William E. Kraus, George A. Truskey |
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| Rok vydání: | 2021 |
| Předmět: |
Senescence
medicine.medical_specialty Vastus lateralis muscle Muscle Fibers Skeletal Biomedical Engineering Medicine (miscellaneous) Inflammation Article Arthritis Rheumatoid Myoblasts Biomaterials Immune system Internal medicine medicine Humans Myocyte Muscle Skeletal Aged Tetanus business.industry Skeletal muscle Middle Aged medicine.disease Endocrinology medicine.anatomical_structure Rheumatoid arthritis medicine.symptom business Muscle Contraction |
| Zdroj: | J Tissue Eng Regen Med |
| ISSN: | 1932-7005 1932-6254 |
| DOI: | 10.1002/term.3266 |
| Popis: | Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily targeting the joints. Autoreactive immune cells involved in RA affect other tissues, including skeletal muscle. Patients with RA experience diminished physical function, limited mobility, reduced muscle function, chronic pain, and increased mortality. To explore the impact of RA on skeletal muscle, we engineered electrically responsive, contractile human skeletal muscle constructs (myobundles) using primary skeletal muscle cells isolated from the vastus lateralis muscle of 11 RA patients (aged 57–74) and 10 aged healthy donors (aged 55–76), as well as from the hamstring muscle of 6 young healthy donors (less than 18 years of age) as a benchmark. Since all patients were receiving treatment for the disease, RA disease activity was mild. In 2D culture, RA myoblast purity, growth rate, and senescence were not statistically different than aged controls; however, RA myoblast purity showed greater variance compared to controls. Surprisingly, in 3D culture, contractile force production by RA myobundles was greater compared to aged controls. In support of this finding, assessment of RA myofiber maturation showed increased area of sarcomeric α-actinin expression over time compared to aged controls. Furthermore, a linear regression test indicated a positive correlation between sarcomeric α-actinin protein levels and tetanus force production in RA and controls. Our findings suggest that medications prescribed to RA patients may maintain—or even enhance—muscle function, and this effect is retained and observed in in vitro culture. Future studies regarding the effects of RA therapeutics on RA skeletal muscle, in vivo and in vitro, are warranted. |
| Databáze: | OpenAIRE |
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