Muscle could be the therapeutic target in SMA treatment

Guettier‐Sigrist, Séverine; Coupin, Gilliane; Braun, Serge; Warter, Jean‐Marie; Poindron, Philippe

doi:10.1002/(sici)1097-4547(19980915)53:6<663::aid-jnr4>3.0.co;2-3

Cited by 51 publications

(32 citation statements)

References 30 publications

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“…Three-dimensional muscle-neuronal co-culture To induce the differentiation and orientation of myoblasts, we have co-cultivated skeletal muscle cells with organotypic slice cultures from rat spinal cord, which have been shown to induce differentiation in a twodimensional culture system (Askanas et al 1987;Braun et al 1997;Guettier-Sigrist et al 1998). The myoblasts differentiate with time to form myotubes in the fibrin matrix (Fig.…”

Section: Fibrin As a Three-dimensional Matrixmentioning

confidence: 99%

“…The construction of muscle tissue in vitro holds promise for the treatment of a variety of prevalent inherited and acquired human diseases, including skeletal myopathies such as Duchenne muscular dystrophy and spinal muscular atrophy (Mooney and Mikos 1999;Guettier-Sigrist et al 1998;DiEdwardo et al 1999). Therapeutic treatments for acquired and inherited skeletal myopathies require the ability either to implant constructs of differentiated muscle tissue or to inject muscle precursor cells into sites of dysfunction for the subsequent formation of muscle tissue (DiEdwardo et al 1999).…”

Section: Introductionmentioning

confidence: 99%

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Expression of Trisk�51, agrin and nicotinic-acetycholine receptor ?-subunit during muscle development in a novel three-dimensional muscle-neuronal co-culture system

Bach

Beier

Stärk

2003

Cell and Tissue Research

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The purpose of our study was to create functional muscle tissue in vitro and to investigate the influence of organotypic neuronal slice cultures from rat spinal cord on the differentiation and function of primary rat myoblasts in a novel three-dimensional culture system. Three-dimensional muscle-neuronal cultures were established by co-cultivating primary rat skeletal muscle cells of newborn rats with organotypic slice cultures of the spinal cord prepared from isogenic rats in a fibrin matrix. These constructs were cultured for up to 4 weeks. Differentiation and fusion of the myoblasts to myofibers was evaluated by analyzing the expression pattern and localization of muscle- and neuron-specific markers. The fibrin matrix provided a suitable environment for three-dimensional myoblast culture. Co-culturing of organotypic spinal cord slices with myoblasts induced the formation of spontaneously contracting multinuclear and parallel-aligned myofibers. Pharmacological tests suggested the formation of neuromuscular junctions. The analysis of neural agrin expression and myogenic desmin, myogenin, MyoD, Trisk 51, and nicotinic-acetycholine receptor (nACh-receptor) epsilon-subunit expression revealed the differentiation of the myoblasts to myofibers. The presented novel three-dimensional co-culture system allows the in vitro investigation of myoblast differentiation and neuron-myoblast interaction. Our results suggest the existence of an alternative pathway for the maturation of the nAChR gamma-subunit to the epsilon-subunit without neural agrin activity.

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Section: Fibrin As a Three-dimensional Matrixmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Trisk�51, agrin and nicotinic-acetycholine receptor ?-subunit during muscle development in a novel three-dimensional muscle-neuronal co-culture system

Bach

Beier

Stärk

2003

Cell and Tissue Research

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“…17 We also proved that this degeneration could not be attributed to the production of a toxic factor or to the lack of secretion of a trophic factor, 18 and that the cells responsible for this degeneration were muscle cells. 19 Based on these observations, we hypothesized that myotubes from SMA patients could be innervated and contracted as normal myotubes, but were unable to produce SMN-dependent signal essential for motoneuron survival. 20 This muscular hypothesis was confirmed by the fact that the deletion of SMN exon 7, the most frequently mutated exon in SMA, led to severe muscular dystrophy, proving that skeletal muscle is a target of the SMN gene defect, and confirming our idea that muscle involvement contributes to the motor defect in human SMA disease.…”

mentioning

confidence: 99%

Reduced expression of nicotinic AChRs in myotubes from spinal muscular atrophy I patients

Arnold¹,

Gueye²,

Guettier‐Sigrist³

et al. 2004

Laboratory Investigation

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Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of motoneurons and skeletal muscle atrophy. In its most severe form, it leads to death before the age of 2 years. While primary degeneration of motor neurons is well established in this disease, and this results in neurogenic atrophy of skeletal muscle, we have previously reported evidence for a primary muscle defect. In this study, we used primary cultures of embryonic human skeletal muscle cells from patients with SMA and from controls to examine the effects of muscle fiber differentiation in the absence of a nerve component. Cultured SMA skeletal muscle cells are unable to fuse correctly to form multinuclear myotubes, the precursors of the myofibers. We also show that agrin-induced aggregates of nicotinic acetylcholine receptors, one of the earliest steps of neuromuscular junction formation, cannot be visualized by confocal microscopy on cells from SMA patients. In binding experiments, we demonstrate that this lack of clustering is due to defective expression of the nicotinic acetylcholine receptors in the myotubes of SMA patients whereas the affinity of a-bungarotoxin for its receptor remains unchanged regardless of muscle cell type (SMA or control). These observations suggest that muscle cells from SMA patients have intrinsic abnormalities that may affect proper formation of the neuromuscular junction. Keywords: spinal muscular atrophy; myotubes; neuromuscular junction; nicotinic acetylcholine receptors; aggregation; binding Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by degeneration of spinal motor neurons leading to a muscle weakness and paralysis. SMA is traditionally classified into three types based on the age of onset and the severity of symptoms. 1 The SMA I or Werdnig-Hoffmann disease is the most severe form. Patients never attain the ability to sit, and their lifespan does not exceed infancy in most cases. SMA II is the intermediate form. Patients are unable to stand or walk unaided, and death usually occurs in adulthood. SMA III or Kugelberg-Welander disease presents a milder phenotype. Patients are able to stand and walk and present a near-normal life expectancy. The gene responsible for all three types of SMA was mapped to the region 5q11.2-13.3 by linkage analysis. [2][3][4][5] This gene, named SMN for 'survival of motor neurons', is mutated in 98% of the SMA patients, and the majority of mutations occur in exon 7. 6 It encodes a ubiquitously expressed SMN protein present in both the cytoplasm and the nucleus. In this last compartment, the SMN protein is concentrated in structures called gems (for 'gemini of coiled bodies') located in the close proximity of Cajal bodies (previously named coiled bodies). 7,8 The SMN protein participates in the formation of the SMN complex, which is associated with small nuclear ribonucleoproteins (snRNP) in the cytoplasm and plays a crucial role in the spliceosomal snRNP assembly. 9 In the nucleus, the SMN complex participates in the regener...

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“…Since the muscles used for coverage sometimes do not have neural transmission, secondary surgeries are carried out to provide neurotization and innervation. Generating new muscle tissue from autologous precursor cells (stem cells) attempts to manage this problem via skeletal muscle tissue engineering (Guettier-Sigrist, 1998). …”

Section: Introductionmentioning

confidence: 99%

An in vitro human skeletal muscle model: coculture of myotubes,neuron-like cells, and the capillary network

Ertan¹,

Kenar²,

Beyzadeoğlu³

et al. 2017

Turk J Biol

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This study reports the generation of a new human muscle tissue equivalent from skeletal muscle-derived stem cells and human umbilical vein endothelial cells (HUVECs). Skeletal muscle stem cells were isolated by the preplate technique and differentiated into neuron-like cells that were positive for neuronal beta-tubulin3 and nestin and negative for the astrocyte marker glial fibrillary acidic protein (GFAP). Coculture of skeletal muscle stem cells with the HUVECs under optimized fetal bovine serum and media conditions resulted in formation of a capillary network among the multinucleated myotubes. The neuron-like cells derived from the human skeletal muscle stem cells were seeded onto vascularized myotubes to obtain the neuromuscular junctions in the coculture. At the end of 24 h of coculture, the neuron-like cells were found to be in association with the myotubes. This model represents a novel complex in vitro human skeletal muscle model containing advanced capillary networks and interacting myotubes and neurons, and it can be used for in vitro drug testing or for skeletal muscle regeneration either through application of cellular therapy or cell-laden tissue-engineered muscle constructs.

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Muscle could be the therapeutic target in SMA treatment

Cited by 51 publications

References 30 publications

Expression of Trisk�51, agrin and nicotinic-acetycholine receptor ?-subunit during muscle development in a novel three-dimensional muscle-neuronal co-culture system

Expression of Trisk�51, agrin and nicotinic-acetycholine receptor ?-subunit during muscle development in a novel three-dimensional muscle-neuronal co-culture system

Reduced expression of nicotinic AChRs in myotubes from spinal muscular atrophy I patients

An in vitro human skeletal muscle model: coculture of myotubes,neuron-like cells, and the capillary network

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