Villalobos Elisa, Mehra Priyanka, Diaz-Manera Jordi
John Walton Muscular Dystrophy Research Centre, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK.
Neuromuscular Disease Unit, Departments of Neurology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigacio Biomedica Sant Pau, Barcelona, Spain.
J Physiol. 2025 Aug 22. doi: 10.1113/JP288924.
Fibro/adipogenic progenitors (FAPs) are muscle-resident stem cells essential for muscle regeneration because of their ability to differentiate into adipocytes and fibroblasts. This differentiation contributes to tissue remodelling and is implicated in the accumulation of fat and fibrotic tissue seen in neuromuscular, cardiovascular and degenerative diseases. FAPs also interact with other muscle cells and modulate inflammation, playing a central role in muscle degeneration across various disease contexts. This review summarises current knowledge on FAP adipogenic differentiation in muscle degeneration and regeneration, with a focus on cardiovascular and neuromuscular diseases, which share common features of impaired muscle remodelling. We discuss established methods for culturing, maintaining, and differentiating FAPs in vitro to support future research. Additionally, we examine FAP subpopulations, key signalling pathways and pharmacological agents influencing FAP differentiation into adipocytes. Understanding these mechanisms offers promising avenues for developing therapeutic strategies to restore muscle homeostasis and slow down pathological muscle remodelling.
成纤维/脂肪生成祖细胞(FAPs)是肌肉驻留干细胞,因其具有分化为脂肪细胞和成纤维细胞的能力,对肌肉再生至关重要。这种分化有助于组织重塑,并与神经肌肉、心血管和退行性疾病中出现的脂肪和纤维化组织积累有关。FAPs还与其他肌肉细胞相互作用并调节炎症,在各种疾病背景下的肌肉退化中发挥核心作用。本综述总结了目前关于FAPs在肌肉退化和再生中脂肪生成分化的知识,重点关注具有肌肉重塑受损共同特征的心血管和神经肌肉疾病。我们讨论了在体外培养、维持和分化FAPs的既定方法,以支持未来的研究。此外,我们研究了FAP亚群、影响FAP分化为脂肪细胞的关键信号通路和药物制剂。了解这些机制为开发恢复肌肉稳态和减缓病理性肌肉重塑的治疗策略提供了有前景的途径。