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Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions

Published inCells, vol. 12, no. 16, 2072
Publication date2023-08-15
First online date2023-08-15
Abstract

Botulinum neurotoxin type-A (BoNT) injections are commonly used as spasticity treatment in cerebral palsy (CP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised, and the BoNT effect on muscle stem cells remains not well defined. This study aims at clarifying the impact of BoNT on growing muscles (1) by analyzing the in vitro effect of BoNT on satellite cell (SC)-derived myoblasts and fibroblasts obtained from medial gastrocnemius microbiopsies collected in young BoNT-naïve children (t0) compared to age ranged typically developing children; (2) by following the effect of in vivo BoNT administration on these cells obtained from the same children with CP at 3 (t1) and 6 (t2) months post BoNT; (3) by determining the direct effect of a single and repeated in vitro BoNT treatment on neuromuscular junctions (NMJs) differentiated from hiPSCs. In vitro BoNT did not affect myogenic differentiation or collagen production. The fusion index significantly decreased in CP at t2 compared to t0. In NMJ cocultures, BoNT treatment caused axonal swelling and fragmentation. Repeated treatments impaired the autophagic–lysosomal system. Further studies are warranted to understand the long-term and collateral effects of BoNT in the muscles of children with CP.

eng
Keywords
  • BoNT cell treatment
  • Adult muscle stem cells
  • Cerebral palsy in young children
  • Collagen
  • Induced pluripotent stem cells
  • Muscle microbiopsy
  • Myogenesis
Funding
  • KU Leuven grant - [C24/18/103]
  • postdoctoral mandate (PDM) type 1 of KU Leuven - [PDMT1/21/037]
  • KU Leuven Biomedical Science group: Fund for Translational Biomedical Research 2019 -
  • Erasmus Placement 2021 from University of Turin -
  • Scientific Research Flanders - [G0B4619N]
Citation (ISO format)
COSTAMAGNA, Domiziana et al. Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions. In: Cells, 2023, vol. 12, n° 16, p. 2072. doi: 10.3390/cells12162072
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Identifiers
ISSN of the journal2073-4409
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