Dataset Information

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy.

ABSTRACT: 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.

SUBMITTER: Corvelyn M

PROVIDER: S-EPMC7424076 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy.

Corvelyn Marlies M De Beukelaer Nathalie N Duelen Robin R Deschrevel Jorieke J Van Campenhout Anja A Prinsen Sandra S Gayan-Ramirez Ghislaine G Maes Karen K Weide Guido G Desloovere Kaat K Sampaolesi Maurilio M Costamagna Domiziana D

Frontiers in physiology 20200806

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 muscl ...[more]

PMID: 32848872

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Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies. Skeletal muscle biopsies from both the gracilis and semitendinosus were obtained during surgery for 20 pediatric subjects for affymetrix microarray analysis. We obtained a group of 10 patients undergoing medial hamstring lengthening in the cerebral palsy group and 10 patients undergoing ACL reconstruction with hamstring autograft in the control group. This provided 40 microarrays in 4 groups to analyze the effect of cerebral palsy and also differences between muscles.

Project description:Background: Walking problems in children with cerebral palsy (CP) can in part be explained by limited selective motor control. Muscle synergy analysis is increasingly used to quantify altered neuromuscular control during walking. The early brain injury in children with CP may lead to a different development of muscle synergies compared to typically developing (TD) children, which might characterize the abnormal walking patterns. Objective: The overarching aim of this review is to give an overview of the existing studies investigating muscle synergies during walking in children with CP compared to TD children. The main focus is on how muscle synergies differ between children with CP and TD children, and we examine the potential of muscle synergies as a measure to quantify and predict treatment outcomes. Methods: Bibliographic databases were searched by two independent reviewers up to 22 April 2019. Studies were included if the focus was on muscle synergies of the lower limbs during walking, obtained by a matrix factorization algorithm, in children with CP. Results: The majority (n = 12) of the 16 included studies found that children with CP recruited fewer muscle synergies during walking compared to TD children, and several studies (n = 8) showed that either the spatial or temporal structure of the muscle synergies differed between children with CP and TD children. Variability within and between subjects was larger in children with CP than in TD children, especially in more involved children. Muscle synergy characteristics before treatments to improve walking function could predict treatment outcomes (n = 3). Only minimal changes in synergies were found after treatment. Conclusions: The findings in this systematic review support the idea that children with CP use a simpler motor control strategy compared to TD children. The use of muscle synergy analysis as a clinical tool to quantify altered neuromuscular control and predict clinical outcomes seems promising. Further investigation on this topic is necessary, and the use of muscle synergies as a target for development of novel therapies in children with CP could be explored.

Project description:Muscle weakness is a common clinical symptom in children with spastic cerebral palsy (SCP). It is caused by impaired neural ability and altered intrinsic capacity of the muscles. To define the contribution of decreased muscle size to muscle weakness, two cohorts were recruited in this cross-sectional investigation: 53 children with SCP [median age, 8.2 (IQR, 4.1) years, 19/34 uni/bilateral] and 31 children with a typical development (TD) [median age, 9.7 (IQR, 2.9) years]. Muscle volume (MV) and muscle belly length for m. rectus femoris, semitendinosus, gastrocnemius medialis, and tibialis anterior were defined from three-dimensional freehand ultrasound acquisitions. A fixed dynamometer was used to assess maximal voluntary isometric contractions for knee extension, knee flexion, plantar flexion, and dorsiflexion from which maximal joint torque (MJT) was calculated. Selective motor control (SMC) was assessed on a 5-point scale for the children with SCP. First, the anthropometrics, strength, and muscle size parameters were compared between the cohorts. Significant differences for all muscle size and strength parameters were found (p ≤ 0.003), except for joint torque per MV for the plantar flexors. Secondly, the associations of anthropometrics, muscle size, gross motor function classification system (GMFCS) level, and SMC with MJT were investigated using univariate and stepwise multiple linear regressions. The associations of MJT with growth-related parameters like age, weight, and height appeared strongest in the TD cohort, whereas for the SCP cohort, these associations were accompanied by associations with SMC and GMFCS. The stepwise regression models resulted in ranges of explained variance in MJT from 29.3 to 66.3% in the TD cohort and from 16.8 to 60.1% in the SCP cohort. Finally, the MJT deficit observed in the SCP cohort was further investigated using the TD regression equations to estimate norm MJT based on height and potential MJT based on MV. From the total MJT deficit, 22.6-57.3% could be explained by deficits in MV. This investigation confirmed the disproportional decrease in muscle size and muscle strength around the knee and ankle joint in children with SCP, but also highlighted the large variability in the contribution of muscle size to muscle weakness.

Dataset Information

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy.

Publications

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy.

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