Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy
Cerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell...
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Frontiers Media S.A.
2020-08-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00945/full |
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author | Marlies Corvelyn Nathalie De Beukelaer Robin Duelen Jorieke Deschrevel Anja Van Campenhout Sandra Prinsen Ghislaine Gayan-Ramirez Karen Maes Guido Weide Guido Weide Kaat Desloovere Maurilio Sampaolesi Domiziana Costamagna Domiziana Costamagna |
author_facet | Marlies Corvelyn Nathalie De Beukelaer Robin Duelen Jorieke Deschrevel Anja Van Campenhout Sandra Prinsen Ghislaine Gayan-Ramirez Karen Maes Guido Weide Guido Weide Kaat Desloovere Maurilio Sampaolesi Domiziana Costamagna Domiziana Costamagna |
author_sort | Marlies Corvelyn |
collection | DOAJ |
description | Cerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell (SC) numbers and hypertrophic extracellular matrix compared to typically developing (TD) children (>10 years). Unfortunately, data on younger CP patients are scarce and studies on SCs and other muscle stem cells in CP are insufficient or lacking. Therefore, it remains difficult to understand the early onset and trajectory of altered muscle properties in growing CP children. Because muscle stem cells are responsible for postnatal growth, repair and remodeling, multiple adult stem cell populations from young CP children could play a role in altered muscle development. To this end, new methods for studying muscle samples of young children, valid to delineate the features and to elucidate the regenerative potential of muscle tissue, are necessary. Using minimal invasive muscle microbiopsy, which was applied in young subjects under general anaesthesia for the first time, we aimed to isolate and characterize muscle stem cell-derived progenitors of TD children and patients with CP. Data of 15 CP patients, 3–9 years old, and 5 aged-matched TD children were reported. The muscle microbiopsy technique was tolerated well in all participants. Through the explant technique, we provided muscle stem cell-derived progenitors from the Medial Gastrocnemius. Via fluorescent activated cell sorting, using surface markers CD56, ALP, and PDGFRa, we obtained SC-derived progenitors, mesoangioblasts and fibro-adipogenic progenitors, respectively. Adipogenic, skeletal, and smooth muscle differentiation assays confirmed the cell identity and ability to give rise to different cell types after appropriate stimuli. Myogenic differentiation in CP SC-derived progenitors showed enhanced fusion index and altered myotube formation based on MYOSIN HEAVY CHAIN expression, as well as disorganization of nuclear spreading, which were not observed in TD myotubes. In conclusion, the microbiopsy technique allows more focused muscle research in young CP patients. Current results show altered differentiation abilities of muscle stem cell-derived progenitors and support the hypothesis of their involvement in CP-altered muscle growth. |
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spelling | doaj.art-9a0d3f59d3984f92b7f8851955d14b3b2022-12-21T19:34:07ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-08-011110.3389/fphys.2020.00945542425Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral PalsyMarlies Corvelyn0Nathalie De Beukelaer1Robin Duelen2Jorieke Deschrevel3Anja Van Campenhout4Sandra Prinsen5Ghislaine Gayan-Ramirez6Karen Maes7Guido Weide8Guido Weide9Kaat Desloovere10Maurilio Sampaolesi11Domiziana Costamagna12Domiziana Costamagna13Stem Cell Biology and Embryology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumNeurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, Leuven, BelgiumStem Cell Biology and Embryology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumLaboratory of Respiratory Disease and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, BelgiumPediatric Orthopedics, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumPediatric Orthopedics, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumLaboratory of Respiratory Disease and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, BelgiumLaboratory of Respiratory Disease and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, BelgiumNeurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, Leuven, BelgiumLaboratory of Respiratory Disease and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, BelgiumNeurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, Leuven, BelgiumStem Cell Biology and Embryology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumStem Cell Biology and Embryology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumNeurorehabilitation Group, Department of Rehabilitation Sciences, KU Leuven, Leuven, BelgiumCerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell (SC) numbers and hypertrophic extracellular matrix compared to typically developing (TD) children (>10 years). Unfortunately, data on younger CP patients are scarce and studies on SCs and other muscle stem cells in CP are insufficient or lacking. Therefore, it remains difficult to understand the early onset and trajectory of altered muscle properties in growing CP children. Because muscle stem cells are responsible for postnatal growth, repair and remodeling, multiple adult stem cell populations from young CP children could play a role in altered muscle development. To this end, new methods for studying muscle samples of young children, valid to delineate the features and to elucidate the regenerative potential of muscle tissue, are necessary. Using minimal invasive muscle microbiopsy, which was applied in young subjects under general anaesthesia for the first time, we aimed to isolate and characterize muscle stem cell-derived progenitors of TD children and patients with CP. Data of 15 CP patients, 3–9 years old, and 5 aged-matched TD children were reported. The muscle microbiopsy technique was tolerated well in all participants. Through the explant technique, we provided muscle stem cell-derived progenitors from the Medial Gastrocnemius. Via fluorescent activated cell sorting, using surface markers CD56, ALP, and PDGFRa, we obtained SC-derived progenitors, mesoangioblasts and fibro-adipogenic progenitors, respectively. Adipogenic, skeletal, and smooth muscle differentiation assays confirmed the cell identity and ability to give rise to different cell types after appropriate stimuli. Myogenic differentiation in CP SC-derived progenitors showed enhanced fusion index and altered myotube formation based on MYOSIN HEAVY CHAIN expression, as well as disorganization of nuclear spreading, which were not observed in TD myotubes. In conclusion, the microbiopsy technique allows more focused muscle research in young CP patients. Current results show altered differentiation abilities of muscle stem cell-derived progenitors and support the hypothesis of their involvement in CP-altered muscle growth.https://www.frontiersin.org/article/10.3389/fphys.2020.00945/fullcerebral palsyyoung childrenmuscle microbiopsyadult muscle stem cell-derived progenitorsdifferentiation potentialmyogenesis |
spellingShingle | Marlies Corvelyn Nathalie De Beukelaer Robin Duelen Jorieke Deschrevel Anja Van Campenhout Sandra Prinsen Ghislaine Gayan-Ramirez Karen Maes Guido Weide Guido Weide Kaat Desloovere Maurilio Sampaolesi Domiziana Costamagna Domiziana Costamagna Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy Frontiers in Physiology cerebral palsy young children muscle microbiopsy adult muscle stem cell-derived progenitors differentiation potential myogenesis |
title | Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy |
title_full | Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy |
title_fullStr | Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy |
title_full_unstemmed | Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy |
title_short | Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy |
title_sort | muscle microbiopsy to delineate stem cell involvement in young patients a novel approach for children with cerebral palsy |
topic | cerebral palsy young children muscle microbiopsy adult muscle stem cell-derived progenitors differentiation potential myogenesis |
url | https://www.frontiersin.org/article/10.3389/fphys.2020.00945/full |
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