Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skeletal muscle cells.
Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skeletal muscle cells.
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DOI：
10.1002/term.3266
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发表时间：
2022-03
影响因子：
3.3
通讯作者：
Truskey, George A.
中科院分区：
文献类型：
--
作者：
Oliver, Catherine E.;Patel, Hailee;Hong, James;Carter, Jonathan;Kraus, William E.;Huffman, Kim M.;Truskey, George A.
类风湿关节炎（RA）是一种主要累及关节的慢性炎症性疾病。参与RA的自身反应性免疫细胞会影响其他组织，包括骨骼肌。RA患者会出现身体机能下降、活动受限、肌肉功能减退、慢性疼痛以及死亡率增加等情况。为了探究RA对骨骼肌的影响，我们利用从11名RA患者（年龄57 - 74岁）的股外侧肌、10名老年健康供体（年龄55 - 76岁）以及6名年轻健康供体（年龄小于18岁）的腘绳肌中分离出的原代骨骼肌细胞构建了电响应性、可收缩的人类骨骼肌结构（肌束），并将年轻健康供体作为基准。由于所有患者都在接受针对该疾病的治疗，RA疾病活动度较轻。在二维培养中，RA成肌细胞的纯度、生长速率和衰老情况与老年对照组相比无统计学差异；然而，与对照组相比，RA成肌细胞纯度的差异更大。令人惊讶的是，在三维培养中，RA肌束产生的收缩力比老年对照组更大。为支持这一发现，对RA肌纤维成熟度的评估显示，与老年对照组相比，随着时间推移，肌节α - 辅肌动蛋白表达面积增加。此外，线性回归测试表明，在RA患者和对照组中，肌节α - 辅肌动蛋白水平与破伤风收缩力产生呈正相关。我们的研究结果表明，给RA患者开具的药物可能维持甚至增强肌肉功能，并且这种效应在体外培养中得以保留和观察到。未来有必要在体内和体外对RA治疗药物对RA骨骼肌的影响进行研究。
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.
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DOI：
10.1002/art.23719
发表时间：
2008-06-15
期刊：
ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
影响因子：
--
作者：
Giles, Jon T.;Ling, Shari M.;Bathon, Joan M.
通讯作者：
Bathon, Joan M.
影响因子：
5.5
作者：
Lemmey, Andrew B.;Wilkinson, Thomas J.;O'Brien, Thomas D.
通讯作者：
O'Brien, Thomas D.
DOI：
10.1152/ajpregu.2000.279.6.r2156
发表时间：
2000-12-01
影响因子：
2.8
作者：
Alloatti, G;Penna, C;Camussi, G
通讯作者：
Camussi, G
影响因子：
5.4
作者：
Asquith, Darren L.;Miller, Ashley M.;Liew, Foo Y.
通讯作者：
Liew, Foo Y.
影响因子：
--
作者：
Oyenihi, A. B.;Ollewagen, T.;Smith, C.
通讯作者：
Smith, C.