Gandolfi S, Pileyre B, Drouot L, Dubus I, Auquit-Auckbur I, Martinet J
Univ Rouen Normandie, INSERM U1234, FOCIS Center of Excellence PAn'THER, F-76000, Rouen, France.
Toulouse University Hospital, Department of Plastic and Reconstructive Surgery, F-31000, Toulouse, France.
Cell Death Discov. 2023 Sep 19;9(1):346. doi: 10.1038/s41420-023-01605-9.
Muscle regeneration is a physiological process that converts satellite cells into mature myotubes under the influence of an inflammatory environment progressively replaced by an anti-inflammatory environment, with precise crosstalk between immune and muscular cells. If the succession of these phases is disturbed, the immune system can sometimes become auto-reactive, leading to chronic muscular inflammatory diseases, such as myositis. The triggers of these autoimmune myopathies remain mostly unknown, but the main mechanisms of pathogenesis are partially understood. They involve chronic inflammation, which could be associated with an auto-reactive immune response, and gradually with a decrease in the regenerative capacities of the muscle, leading to its degeneration, fibrosis and vascular architecture deterioration. Immunosuppressive treatments can block the first part of the process, but sometimes muscle remains weakened, or even still deteriorates, due to the exhaustion of its capacities. For patients refractory to immunosuppressive therapies, mesenchymal stem cells have shown interesting effects but their use is limited by their availability. Stromal vascular fraction, which can easily be extracted from adipose tissue, has shown good tolerance and possible therapeutic benefits in several degenerative and autoimmune diseases. However, despite the increasing use of stromal vascular fraction, the therapeutically active components within this heterogeneous cellular product are ill-defined and the mechanisms by which this therapy might be active remain insufficiently understood. We review herein the current knowledge on the mechanisms of action of stromal vascular fraction and hypothesise on how it could potentially respond to some of the unmet treatment needs of refractory myositis.
肌肉再生是一个生理过程,在炎症环境的影响下,卫星细胞会逐渐转变为成熟的肌管,随后炎症环境会被抗炎环境逐步取代,在此过程中免疫细胞与肌肉细胞之间存在精确的相互作用。如果这些阶段的连续性受到干扰,免疫系统有时会产生自身反应,从而引发慢性肌肉炎症性疾病,如肌炎。这些自身免疫性肌病的触发因素大多仍不明确,但发病机制的主要方面已部分得到了解。其机制涉及慢性炎症,这可能与自身反应性免疫反应相关,并逐渐导致肌肉再生能力下降,进而引发肌肉退化、纤维化以及血管结构恶化。免疫抑制治疗可以阻断该过程的第一部分,但由于肌肉功能耗尽,有时肌肉仍会保持虚弱状态,甚至继续恶化。对于免疫抑制疗法难治的患者,间充质干细胞已显示出有意义的效果,但其应用受到可用性的限制。可轻松从脂肪组织中提取的基质血管成分,在几种退行性疾病和自身免疫性疾病中已显示出良好的耐受性和可能的治疗益处。然而,尽管基质血管成分的使用越来越多,但这种异质性细胞产物中的治疗活性成分尚不明确,该疗法可能发挥作用的机制也仍未得到充分理解。我们在此回顾了关于基质血管成分作用机制的现有知识,并推测它如何可能满足难治性肌炎一些未得到满足的治疗需求。