Muscle satellite cells and fibro‐adipogenic progenitors from muscle contractures of children with cerebral palsy have impaired regenerative capacity

• DOI: 10.1111/dmcn.16006
• Publication Date: 2024-06-28T04:59:57Z
• Authors: Taryn Loomis; Vedant A. Kulkarni; Marie Villalba; Jon R. Davids; J. Kent Leach; Lucas R. Smith
• Keywords: Male; 0301 basic medicine; Contracture; Biomedical and clinical sciences; Skeletal Muscle; Adolescent; 612; Medical and Health Sciences; Pediatrics; 03 medical and health sciences; Health Sciences; Humans; Regeneration; Psychology; Child; Preschool; Sports Science and Exercise; Pediatric; Cerebral Palsy; Stem Cells; Rehabilitation; Health sciences; Cell Differentiation; Skeletal; Perinatal Period - Conditions Originating in Perinatal Period; Stem Cell Research; Brain Disorders; Satellite Cells; Musculoskeletal; Muscle; Stem Cell Research - Nonembryonic - Non-Human; Female; Original Article

AbstractAimTo evaluate the mechanosensitivity of muscle satellite cells (MuSCs) and fibro‐adipogenic progenitors (FAPs) in cerebral palsy (CP) and the efficacy of the drug verteporfin in restoring cells' regenerative capacity.MethodMuscle biopsies were collected from six children with CP and six typically developing children. MuSCs and FAPs were isolated and plated on collagen‐coated polyacrylamide gels at stiffnesses of 0.2 kPa, 8 kPa, and 25 kPa. Cells were treated with verteporfin to block mechanosensing or with dimethyl sulfoxide as a negative control. MuSC differentiation and FAP activation into myofibroblasts were measured using immunofluorescence staining.ResultsSurprisingly, MuSC differentiation was not affected by stiffness; however, stiff substrates resulted in large myonuclear clustering. Across all stiffnesses, MuSCs from children with CP had less differentiation than those of their typically developing counterparts. FAP activation into myofibroblasts was significantly higher in children with CP than their typically developing peers, but was not affected by stiffness. Verteporfin did not affect differentiation or activation in either cell population, but slightly decreased myonuclear clustering on stiff substrates.InterpretationCells from children with CP were less regenerative and more fibrotic compared to those of their typically developing counterparts, with MuSCs being sensitive to increases in stiffness. Therefore, the mechanosensitivity of MuSCs and FAPs may represent a new target to improve differentiation and activation in CP muscle.