Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1109 - 1109

Published: May 3, 2025

Background: Three-dimensional skeletal muscle organoids (3D SkMO) are becoming of increasing interest for preclinical studies in Duchenne muscular dystrophy (DMD), provided that the used platform demonstrates possibility to form functional and reproducible 3D SkMOs, investigate on potential patient-related phenotypic differences. Methods: In this study, we employed fibrin-based derived from immortalized myogenic precursors DMD patients carrying either a stop codon mutation exon 59 or 48–50 deletion. We compared dystrophic lines with healthy wild-type control (HWT) by assessing microtissue formation ability, contractile function at multiple timepoints along intracellular calcium dynamics via imaging, as well expression markers. Results: found patient-specific structural differences early stages SkMO development. Contractile force, measured both single twitch tetanic responses, was significantly lower SkMOs HWT, most pronounced observed day 7 differentiation. However, these disparities diminished over time under similar culturing conditions absence continuous nerve-like stimulation, suggesting primary deficit lies delayed maturation, also supported gene analysis. Conclusions: Our results underline that, despite initial maturation delay, retain capacity once intrinsic lag is overcome. This suggests critical role dystrophin development, while contraction-induced stress and/or an inflammatory microenvironment essential fully recapitulate phenotypes SkMOs.

Language: Английский