Preclinical efficacy of adipose-derived cell therapies for the treatment of myositis

脂肪来源细胞疗法治疗肌炎的临床前疗效

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Abstract

IMPORTANCE: Idiopathic inflammatory myopathies, commonly referred as myositis, are autoimmune diseases that cause muscle damage, progressive weakness, and disability. Current treatments, including corticosteroids and immunosuppressants, have significant limitations, highlighting the need for new therapies. OBJECTIVE: This preclinical study explored the therapeutic potential of adipose tissue-derived cell therapies, specifically stromal vascular fraction (SVF) and adipose-derived stem cells (ADSC), using an Icos-/- NOD mouse model of spontaneous myositis. DESIGN: SVF and ADSC were extracted from CD1 female mice adipose tissue and cultured. Various doses were injected intramuscularly into the right hind limb of 20- to 22-week-old female Icos-/- NOD mice with a control group. The therapeutic effects were assessed through clinical scoring, grip strength test, and motor function analysis using Catwalk system. Muscle atrophy was evidenced by histology, and systemic inflammation was analyzed by flow cytometry. RESULTS: Mice treated with either SVF or ADSC showed a dose-dependent slowdown in disease progression and improvements in motor functions, such as gait, movement, speed, and weight distribution between the legs. Histological analysis showed a reduction in muscular atrophy, particularly in the injected limb. Flow cytometry analysis on lymph nodes showed shifts in leukocyte populations, with reduced expression of inflammatory and activation markers. CONCLUSIONS AND RELEVANCE: Overall, this study demonstrated the therapeutic potential intramuscular injection of SVF or ADSC in the Icos-/- NOD mouse model of myositis, providing a proof-of-concept for the use of adipose tissue-derived cell therapies in the treatment of idiopathic inflammatory myopathies.

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