Alterations in Satellite Cell Differentiation from Young Patients with Cerebral Palsy

Abstract

Cerebral Palsy (CP) is one of the most common lifelong conditions leading to childhood physical disability, affecting approximately 1.6 in 1000 live births. Literature reported muscle alterations of CP patients in comparison to Typically Developing (TD) children such as fibrotic tissue accumulation and reduced Satellite Cell (SC) numbers with altered fusion capacity. To better understand the observed CP muscle phenotype, we quantified and investigated SC-progenitors of the Medial Gastrocnemius from young patients with CP (n=17, aged 3-9 years, GMFCS levels I-III) and age-matched TD children (n=12). We found an increased myotube diameter and a higher amount of nucleus clusters in CP-derived myotubes compared to TD-derived myotubes. Additionally, these nucleus accumulations were larger and less linear in SCs from children with CP compared to TD. Further, no altered expression levels of multiple genes associated with SC differentiation, fusion and nuclear positioning involved in other muscle disorders have been observed. In conclusion, we unprecedently quantified altered differentiation features of SCs from CP muscles with unaltered gene hallmarks of myopathies. Further research would be needed to elucidate pathophysiological mechanisms related to the altered SC properties observed in CP muscles and its impact on in vivo muscle functioning.