Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions
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...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2072 |
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| author | Domiziana Costamagna Valeria Bastianini Marlies Corvelyn Robin Duelen Jorieke Deschrevel Nathalie De Beukelaer Hannah De Houwer Maurilio Sampaolesi Ghislaine Gayan-Ramirez Anja Van Campenhout Kaat Desloovere |
| author_facet | Domiziana Costamagna Valeria Bastianini Marlies Corvelyn Robin Duelen Jorieke Deschrevel Nathalie De Beukelaer Hannah De Houwer Maurilio Sampaolesi Ghislaine Gayan-Ramirez Anja Van Campenhout Kaat Desloovere |
| author_sort | Domiziana Costamagna |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:03:58Z |
| format | Article |
| id | doaj.art-ffe2c6984d534492bdb88539d30e63fa |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:03:58Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ffe2c6984d534492bdb88539d30e63fa2023-11-19T00:37:02ZengMDPI AGCells2073-44092023-08-011216207210.3390/cells12162072Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular JunctionsDomiziana Costamagna0Valeria Bastianini1Marlies Corvelyn2Robin Duelen3Jorieke Deschrevel4Nathalie De Beukelaer5Hannah De Houwer6Maurilio Sampaolesi7Ghislaine Gayan-Ramirez8Anja Van Campenhout9Kaat Desloovere10Neurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, 3000 Leuven, BelgiumNeurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, 3000 Leuven, BelgiumStem Cell and Developmental Biology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumStem Cell and Developmental Biology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumLaboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, BelgiumNeurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, 3000 Leuven, BelgiumDepartment of Orthopedic Surgery, University Hospitals Leuven, 3000 Leuven, BelgiumStem Cell and Developmental Biology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumLaboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, BelgiumDepartment of Orthopedic Surgery, University Hospitals Leuven, 3000 Leuven, BelgiumNeurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, 3000 Leuven, BelgiumBotulinum 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.https://www.mdpi.com/2073-4409/12/16/2072cerebral palsy in young childrenBoNT cell treatmentmuscle microbiopsyadult muscle stem cellsinduced pluripotent stem cellsmyogenesis |
| spellingShingle | Domiziana Costamagna Valeria Bastianini Marlies Corvelyn Robin Duelen Jorieke Deschrevel Nathalie De Beukelaer Hannah De Houwer Maurilio Sampaolesi Ghislaine Gayan-Ramirez Anja Van Campenhout Kaat Desloovere Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions Cells cerebral palsy in young children BoNT cell treatment muscle microbiopsy adult muscle stem cells induced pluripotent stem cells myogenesis |
| title | Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions |
| title_full | Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions |
| title_fullStr | Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions |
| title_full_unstemmed | Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions |
| title_short | Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions |
| title_sort | botulinum toxin treatment of adult muscle stem cells from children with cerebral palsy and hipsc derived neuromuscular junctions |
| topic | cerebral palsy in young children BoNT cell treatment muscle microbiopsy adult muscle stem cells induced pluripotent stem cells myogenesis |
| url | https://www.mdpi.com/2073-4409/12/16/2072 |
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