Myopathic Muscle Research Articles

Relationship between wooden breast severity in broiler chicken, antioxidant enzyme activity and markers of energy metabolism

This study aims to provide new insight on the association between the development of wooden breast myopathy and mitochondrial and glycolytic activity under oxidative stress. Myopathic muscle had higher oxidative stress together with altered glycolytic metabolism and tricarboxylic acid (TCA) cycle. This was evidenced by significantly elevated antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase), decreased citrate synthase activity and postmortem glycolytic potential with increasing wooden breast severity. In addition, affected muscles also exhibited higher initial and ultimate pH values as well as reduced total glucose and lactate contents. Citrate synthase activity was negatively correlated to antioxidant enzyme activities. Taken together, we propose that the development of the wooden breast lesion is a chronic process that may be related to the failure of muscle fibers to defend against the excessively generated oxidative products promoted by mitochondrial damage accompanied by impaired TCA cycle. Furthermore, there was a positive correlation between citrate synthase activity and glycolytic potential, which suggests that the wooden breast condition is linked to the overall altered energy metabolism of the muscle, including the oxidative phosphorylation and glycolytic pathways.

Clinical Spectrum of Biopsy Proven Mitochondrial Myopathy.

Clinical spectrum of mitochondrial myopathy extends beyond chronic progressive external ophthalmoplegia (CPEO). While information on encephalomyopathies is abundant, clinical data on predominant myopathic presentation of mitochondrial disorders are lacking. Clinical, electrophysiological, biochemical, and follow-up data of patients with predominant myopathic presentation and muscle biopsy confirmed primary mitochondrial myopathy was obtained. We excluded known syndromes of mitochondrial cytopathies and encephalomyopathies. Among 16 patients, 7 had CPEO, 4 had CPEO with limb-girdle muscle weakness (LGMW), and 5 had isolated LGMW. Systemic features included seizures with photosensitivity (n = 3), diabetes (n = 1), cardiomyopathy (n = 1), and sensorineural hearing loss (n = 1) and were more common in isolated LGMW. Elevated serum creatine kinase (CK) and lactate levels and electromyography (EMG) myopathic potentials were more frequent with LGMW. During follow-up, LGMW had more severe progression of weakness. We identified three subsets of mitochondrial myopathy with distinct clinical features and evolutionary patterns. Isolated LGMW was seen in 30% of patients and would represent severe end of the spectrum.

The hypoxia-inducible factor 1 pathway plays a critical role in the development of breast muscle myopathies in broiler chickens: a comprehensive review.

In light of the increased worldwide demand for poultry meat, genetic selection efforts have intensified to produce broiler strains that grow at a higher rate, have greater breast meat yield (BMY), and convert feed to meat more efficiently. The increased selection pressure for these traits, BMY in particular, has produced multiple breast meat quality defects collectively known as breast muscle myopathies (BMM). Hypoxia has been proposed as one of the major mechanisms triggering the onset and occurrence of these myopathies. In this review, the relevant literature on the causes and consequences of hypoxia in broiler breast muscles is reviewed and discussed, with a special focus on the hypoxia-inducible factor 1 (HIF-1) pathway. Muscle fiber hypertrophy induced by selective breeding for greater BMY reduces the space available in the perimysium and endomysium for blood vessels and capillaries. The hypoxic state that results from the lack of circulation in muscle tissue activates the HIF-1 pathway. This pathway alters energy metabolism by promoting anaerobic glycolysis, suppressing the tricarboxylic acid cycle and damaging mitochondrial function. These changes lead to oxidative stress that further exacerbate the progression of BMM. In addition, activating the HIF-1 pathway promotes fatty acid synthesis, lipogenesis, and lipid accumulation in myopathic muscle tissue, and interacts with profibrotic growth factors leading to increased deposition of matrix proteins in muscle tissue. By promoting lipidosis and fibrosis, the HIF-1 pathway contributes to the development of the distinctive phenotypes of BMM, including white striations in white striping-affected muscles and the increased hardness of wooden breast-affected muscles.

The duration of glucocorticoid treatment alters the anabolic response to high-force muscle contractions.

Glucocorticoids induce a myopathy that includes loss of muscle mass and strength. Resistance exercise may reverse the muscle loss because it induces an anabolic response characterized by increases in muscle protein synthesis and potentially suppressing protein breakdown. Whether resistance exercise induces an anabolic response in glucocorticoid myopathic muscle is unknown, which is a problem because long-term glucocorticoid exposure alters the expression of genes that may prevent an anabolic response by limiting activation of pathways such as the mechanistic target of rapamycin in complex 1 (mTORC1). The purpose of this study was to assess whether high-force contractions initiate an anabolic response in glucocorticoid myopathic muscle. The anabolic response was analyzed by treating female mice with dexamethasone (DEX) for 7 days or 15 days. After treatment, the left tibialis anterior muscle of all mice was contracted via electrical stimulation of the sciatic nerve. Muscles were harvested 4 h after contractions. Rates of muscle protein synthesis were estimated using the SUnSET method. After 7 days of treatment, high-force contractions increased protein synthesis and mTORC1 signaling in both groups. After 15 days of treatment, high-force contractions activated mTORC1 signaling equally in both groups, but protein synthesis was only increased in control mice. The failure to increase protein synthesis may be because baseline synthetic rates were elevated in DEX-treated mice. The LC3 II/I ratio marker of autophagy was decreased by contractions regardless of treatment duration. These data show duration of glucocorticoid treatment alters the anabolic response to high-force contractions.NEW & NOTEWORTHY Glucocorticoid myopathy is the most common, toxic, noninflammatory myopathy. Our work shows that high-force contractions increase protein synthesis in skeletal muscle following short-term glucocorticoid treatment. However, longer duration glucocorticoid treatment results in anabolic resistance to high-force contractions despite activation of the mechanistic target of rapamycin in complex 1 (mTORC1) signaling pathway. This work defines potential limits for high-force contractions to activate the processes that would restore lost muscle mass in glucocorticoid myopathic patients.

High-Intensity Ultrasonication as an Innovative Approach for the Softening of Wooden Breast Meat in Broilers

Considering the remarkable implications exerted by the occurrence of wooden breast (WB) abnormality on meat tenderness and marketability, the poultry processing industry demands the implementation of postmortem procedures that can improve the textural traits of chicken breasts affected by this defect. Within this scenario, this study aimed at exploring the effectiveness of high-intensity ultrasonication (HIU) in attenuating the toughness of WB fillets and evaluating its effects on the main technological properties and quality characteristics of chicken breast meat. Overall outcomes showed that HIU significantly reduced (P<0.01) the compression forces of both unaffected and WB raw meat without negatively affecting the main meat quality traits and technological properties, such as color and water holding capacity. The significant (P<0.05) increase in myofibrillar fragmentation index (MFI) observed in unaffected fillets might hint at an alteration of myofibril integrity following the mechanical action of ultrasonic waves. However, despite the effectiveness of HIUin improving the textural traits of raw WB meat, overall outcomes obtained through western blot and MFI analyses suggested that HIU did not remarkably alter the microstructure of myopathic muscles. The myodegenerative lesions typically occurring in WB muscles may have partially disguised the mechanical effects of ultrasonic waves on muscle cells’ structures, making the elucidation of the mechanisms that lead to the softening of WB meat particularly complex.

Study of emerging chicken meat quality defects using OMICs: What do we know?

Starting in approximately 2010, broiler breast meat myopathies, specifically woody breast meat, white striping, spaghetti meat, and gaping have increased in prevalence in the broiler meat industry. Omic methods have been used to elucidate compositional, genetic, and biochemical differences between myopathic and normal breast meat and have provided information on the factors that contribute to these myopathies. This review paper focuses on the genomic, transcriptomic, proteomic, metabolomic, and other omics research that has been conducted to unravel the molecular mechanisms involved in the development of these myopathies and their associated factors and potential causes. SignificanceThis review manuscript summarizes poultry meat quality defects, also referred to as myopathies, that have been evaluated using omics methods. Genomics, transcriptomics, proteomics, metabolomics and other methodologies have been used to understand the genetic predisposition, the protein expression, and the biochemical pathways that are associated with the expression of woody breast meat, white striping, and other myopathies. This has allowed researchers and the industry to differentiate between chicken breast meat with and without myopathic muscle as well as the environmental and genetic conditions that contribute to differences in biochemical pathways and lead to the phenotypes associate with these different myopathies.

Lactate metabolism is essential in early-onset mitochondrial myopathy.

Myopathies secondary to mitochondrial electron transport chain (ETC) dysfunction can result in devastating disease. While the consequences of ETC defects have been extensively studied in culture, little in vivo data are available. Using a mouse model of severe, early-onset mitochondrial myopathy, we characterized the proteomic, transcriptomic, and metabolic characteristics of disease progression. Unexpectedly, ETC dysfunction in muscle results in reduced expression of glycolytic enzymes in our animal model and patient muscle biopsies. The decrease in glycolysis was mediated by loss of constitutive Hif1α signaling, down-regulation of the purine nucleotide cycle enzyme AMPD1, and activation of AMPK. In vivo isotope tracing experiments indicated that myopathic muscle relies on lactate import to supply central carbon metabolites. Inhibition of lactate import reduced steady-state levels of tricarboxylic acid cycle intermediates and compromised the life span of myopathic mice. These data indicate an unexpected mode of metabolic reprogramming in severe mitochondrial myopathy that regulates disease progression.

Novel truncating variants in FGD1 detected in two Danish families with Aarskog-Scott syndrome and myopathic features.

Aarskog–Scott syndrome (AAS) is a developmental disorder, caused by disease‐causing hemizygous variants in the FGD1 gene. AAS is characterized by dysmorphic features, genital malformation, skeletal anomalies, and in some cases, intellectual disability and behavioral difficulties. Myopathy has only been reported once in two affected siblings diagnosed with AAS. Only few adult cases have been reported. This article reports four adults with AAS (three male cases and one female carrier) from two unrelated Danish families, all males presented with variable features suggestive of myopathy. All four carried novel hemizygous pathogenic variants in the FGD1 gene; one family presented with the c.2266dup, p.Cys756Leufs*19 variant while the c.527dup; p.Leu177Thrfs*40 variant was detected in the second family. All males had some mild myopathic symptoms or histological abnormalities. Case 1 had the most severe myopathic phenotype with prominent proximal muscular fatigue and exercise intolerance. In addition, he had multiple deletions of mtDNA and low respiratory chain activity. His younger nephew, case 3, had difficulties doing sports in his youth and had a mildly abnormal muscle biopsy and relatively decreased mitochondrial enzyme activity. The singular case from family 2 (case 4), had a mildly myopathic muscle biopsy, but no overt myopathic symptoms. Our findings suggest that myopathic involvement should be considered in AAS.

Breast muscle myopathies in broiler: mechanism, status and their impact on meat quality – A review

Abstract Almost a decade ago, the sudden rise of breast muscle defects in fast-growing commercial broiler breeds challenged the broiler production industry and meat scientists to address the issue of these novel muscle abnormalities. After that, a widespread hypothesis showing a correlation between high muscle yield and incidence of these muscle myopathies received much acceptance from the research community. Increased muscle hypertrophy and unbalanced growth of connective tissues lead to an inadequate blood supply that ultimately causes hypoxia in muscle fibers. Reduced blood vascular density in muscle fibers induces oxidative stress and mitochondrial dysfunction, leading to muscle fibrosis, lipidosis and myodegeneration. Along with physical changes, the myopathic muscles exhibit poor sensory properties, abnormal texture properties and a low nutritional profile. As these myopathies alter meat’s physical appearance, they have a negative impact on customer’s behavior and preference. A better production environment with proper dietary supplementation with balanced breeding strategies can minimize the incidence of muscle myopathies in broiler chicken. This review aims to address the underlying mechanism behind these myopathies and their impact on poultry meat quality, including nutritional value and consumer behavior. It describes the link between genetic and non-genetic elements influencing myopathies, along with the strategies to minimize the occurrence of breast muscle myopathies.

Clinical and histopathological features of myositis in systemic lupus erythematosus

ObjectiveThe objectives of this study were to compare the clinical features of patients with SLE with and without myopathy and to describe the muscle biopsy features of patients with SLE...

CONGENITAL MYOPATHIES – NEMALINE MYOPATHIES: EP.43 Utilization of RNA sequencing to diagnose and to provide mechanistic insight in NEB-related myopathy

The congenital myopathies are a genetically heterogenous group of skeletal muscle disorders characterized by early onset muscle weakness and variable myopathic findings on muscle biopsy, of which a third of patients remain genetically uncharacterized. Biallelic variants in NEB, encoding nebulin, are a known cause for nemaline myopathy; however, given NEB’s 183 exon expanse, and complexity of resulting isoforms, the functional impact of variants can be difficult to interpret. RNA sequencing is an emerging tool for understanding how such variants impact transcription and cause disease. Recently it has been shown that NEB contains alternatively spliced exons 143 and 144 (E144) and a role for specific isoforms in myogenesis and fiber typing has been postulated, with E144 showing predominant inclusion in the adult isoform of nebulin. We present two brothers (11 and 15 years) with congenital myopathy with myopathic muscle biopsy findings without nemaline rods, normal CK, myopathic findings on EMG, and normal cardiac and pulmonary function. Quartet exome sequencing identified compound heterozygous variants in NEB (NM_001271208.2), a maternally inherited p.Cys693Ter and a paternally inherited c.21522+3A>G splice variant with unknown impact as it is adjacent to alternatively spliced E144. To evaluate this variant, we did RNA sequencing on muscle tissue. Patient's transcriptome showed skipping of E144, in contrast to controls who express a transcript ratio of approximately 1:4 (143:144), suggesting that the disease may partially be driven by a lack of NEB E144 inclusion, affecting the predominant adult isoform. Given this evidence, we compared patterns of muscle involvement from MRI to the literature to assess if the pattern of involvement in our patient correlated to relative expression of E144 in adult muscle. This case highlights the usefulness of RNA sequencing in evaluating variants and for providing insight into the potential role of isoforms in disease pathogenesis.

The insidious impact of under-diagnosed proximal weakness induced by statins

ABSTRACT Introduction: This Perspective reassesses the consensus opinion that statin-associated muscle symptoms (SAMS) occur in <1% of users and associated myopathic proximal muscle weakness is even more rare. Areas covered: Of the over 180,000 participants in clinical trials and large registries of statin users, only a few studies have included a standard manual muscle test (MMT), dynamometry or a focused questionnaire to assess for proximal weakness and related disability in daily and recreational activities. Formal strength testing suggests, however, that weakness can be demonstrated in at least 10% of users. Expert opinion: Reporting inaccuracies about SAMS, confirmation bias among experts and physicians, absence of a standard questionnaire regarding the potential consequences of weakness on physical capacity, and the failure to routinely perform an objective assessment of strength may have led to under-diagnosis of statin-induced myopathy. A brief MMT before cholesterol-lowering agents are started and at follow-up visits, a 12-week withdrawal of the statin in the presence of new paresis without an alternative cause, and the exam finding that strength recovers off the statin are necessary to assess the incidence of drug-induced proximal weakness and inform alternative therapeutic strategies.

Soluble dimeric prion protein ligand activates Adgrg6 receptor but does not rescue early signs of demyelination in PrP-deficient mice.

The adhesion G-protein coupled receptor Adgrg6 (formerly Gpr126) is instrumental in the development, maintenance and repair of peripheral nervous system myelin. The prion protein (PrP) is a potent activator of Adgrg6 and could be used as a potential therapeutic agent in treating peripheral demyelinating and dysmyelinating diseases. We designed a dimeric Fc-fusion protein comprising the myelinotrophic domain of PrP (FT2Fc), which activated Adgrg6 in vitro and exhibited favorable pharmacokinetic properties for in vivo treatment of peripheral neuropathies. While chronic FT2Fc treatment elicited specific transcriptomic changes in the sciatic nerves of PrP knockout mice, no amelioration of the early molecular signs demyelination was detected. Instead, RNA sequencing of sciatic nerves revealed downregulation of cytoskeletal and sarcomere genes, akin to the gene expression changes seen in myopathic skeletal muscle of PrP overexpressing mice. These results call for caution when devising myelinotrophic therapies based on PrP-derived Adgrg6 ligands. While our treatment approach was not successful, Adgrg6 remains an attractive therapeutic target to be addressed in other disease models or by using different biologically active Adgrg6 ligands.

EP21 Tumour necrosis factor inhibitor for the treatment of refractory extra-pulmonary disease including sarcoid arthritis and myositis

EP21 Tumour necrosis factor inhibitor for the treatment of refractory extra-pulmonary disease including sarcoid arthritis and myositis

NEW GENES AND DISEASES / NGS & RELATED TECHNIQUES: P.333 Progressive proximal muscle weakness, myopathic muscle biopsy and a novel candidate gene

More than 200 new Mendelian disease gene discoveries have been published every year since the introduction of next-generation sequencing technologies. To date, almost 600 genes are associated with neuromuscular disorders. We present the phenotype of an Estonian girl harboring variants in a novel muscle disease candidate gene. The female patient was first noted to have exercise intolerance at age 3 years. Two years later, she presented with abnormal gait, toe walking, frequent falls, lumbar hyperlordosis, hyperextention of the knees, and valgus feet.

Fiber Metabolism, Procollagen and Collagen Type III Immunoreactivity in Broiler Pectoralis Major Affected by Muscle Abnormalities.

Simple SummaryThe impressive production performances achieved by the modern chicken hybrids selected for meat production have indirectly predisposed the pectoral muscle to the onset and progression of abnormalities (i.e., white striping, wooden breast, and spaghetti meat). These myopathies affect the pectoralis major, with a high incidence rate and result in relevant economic losses for the poultry industry due to downgrading of the affected meat. These muscular abnormalities have been often associated with changes in ether the metabolism of the fibers (i.e., a shift from type IIB towards type IIA fibers) or to an increased deposition of collagen up to fibrosis. As collagen type III is typically observed in regenerating muscles, this and its precursor (procollagen type III) might play a role in the cellular processes, resulting in the development of white striping, wooden breast, and spaghetti meat abnormalities. According to our findings, both morphology and metabolism of the fibers were remarkably affected by the occurrence muscular abnormalities that are also associated with a profound modification in the connective tissue architecture. Intriguingly, an altered metabolism and an evident difference in the presence and distribution of procollagen and collagen type III was even observed in pectoralis major muscle from cases classified as unaffected.The present study aimed to evaluate the muscle fiber metabolism and assess the presence and distribution of both procollagen and collagen type III in pectoralis major muscles affected by white striping (WS), wooden breast (WB), and spaghetti meat (SM), as well as in those with macroscopically normal appearance (NORM). For this purpose, 20 pectoralis major muscles (five per group) were selected from the same flock of fast-growing broilers (Ross 308, males, 45-days-old, 3.0 kg live weight) and were used for histochemical (nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) and alpha-glycerophosphate dehydrogenase (α-GPD)) and immunohistochemical (procollagen and collagen type III) analyses. When compared to NORM, we found an increased proportion (p < 0.001) of fibers positively stained to NADH-TR in myopathic muscles along with a relevant decrease (p < 0.001) in the percentage of those exhibiting a positive reaction to α-GPD. In addition, an increased proportion of fibers exhibiting a positive reaction to both stainings was observed in SM, in comparison with NORM (14.3 vs. 7.2%; p < 0.001). After reacting to NADH-TR, SM exhibited the lowest (p < 0.001) cross-sectional area (CSA) of the fibers (−12% with respect to NORM). On the other hand, after reacting to α-GPD, the CSA of WS was found to be significantly larger (+10%) in comparison with NORM (7480 vs. 6776 µm2; p < 0.05). A profound modification of the connective tissue architecture involving a different presence and distribution of procollagen and collagen type III was observed. Intriguingly, an altered metabolism and differences in the presence and distribution of procollagen and collagen type III were even observed in pectoralis major muscle classified as NORM.

Exploring the Factors Contributing to the High Ultimate pH of Broiler Pectoralis Major Muscles Affected by Wooden Breast Condition.

The elevated ultimate pH (pHu) found in wooden breast (WB) meat suggests an altered muscular energetic status in WB but also could be related to a prematurely terminated post-mortem pH decline. The aims of this study were to explore the factors contributing to the elevated pHu and establish whether the occurrence of WB defect alters muscle post-mortem carbohydrate metabolism and determine if the contractile apparatus reflects such changes. A total of 24 carcasses from Ross 308 male chickens were obtained from a commercial producer and harvested using commercial processing procedures. Carcasses were categorized into unaffected (NORM) and WB groups (n = 12 each), and samples were collected from cranial bone-in pectoralis major (PM) muscles at 15 min and 24 h post-mortem for the determination of pH, glycolytic metabolites, adenonucleotides, buffering capacity, phosphofructokinase (PFK) activity, and in vitro pH decline. Twenty-four additional deboned PM samples (12 NORM and 12 WB) were collected from the same processing plant to assess muscle histology and sarcomere length at four different locations throughout the PM muscle. Data show that the reduced glycolytic potential of WB muscles only partially explains the higher (P < 0.001) pHu of WB meat, as residual glycogen along with unaltered PFK activity suggests that neither glycogen nor a deficiency of PFK is responsible for arresting glycolysis prematurely. The dramatic reduction in ATP concentrations in the early post-mortem period suggests a defective ATP-generating pathway that might be responsible for the reduced pH decline in WB samples. Further, the addition of excess of ATPase extended post-mortem glycolysis of WB meat in an in vitro glycolytic system. WB-affected samples have longer (P < 0.001) sarcomeres compared to NORM, indicating the existence of compromised energy-generating pathways in myopathic muscles that may have had consequences on the muscle contraction and tension development, as in vivo, also during the post-mortem period. Considering the overall reduced glycolytic potential and the myodegenerative processes associated with WB condition, we speculate that the higher pHu of WB meat might be the outcome of a drastically impaired energy-generating pathway combined with a deficiency and/or a dysfunction of muscle ATPases, having consequences also on muscle fiber contraction degree.

Physiochemical properties, protein and metabolite profiles of muscle exudate of chicken meat affected by wooden breast myopathy

The current study was designed to investigate the physiochemical properties, protein and metabolite profiles of muscle exudate obtained from chicken breast fillets affected by wooden breast (WB) myopathy. Twenty-four fillets were categorized into varying degrees of WB condition including normal, moderate and severe. Results indicated that exudate loss, free hemoglobin concentration, protein and lipid oxidation were affected by WB myopathy. Electrophoresis analysis showed eight distinct protein bands of differential relative abundance in WB samples compared with the normal, and the identified proteins were mostly involved in carbohydrate metabolic process. 1H nuclear magnetic resonance-based metabolomics identified eleven metabolites including amino acids, nucleotides and organic acid as the most influential metabolites affected by WB myopathy. Overall, this study shows differential molecular profiles of myopathic chicken muscle exudate, and provides a valuable resource for further recognition of WB myopathy.

Significance of Asymptomatic Hyper Creatine-Kinase Emia.

Whether asymptomatic hyper-CKemia (AHCE) should prompt a thorough work-up for muscle disease or not is controversially discussed. This review aims at summarizing and discussing recent findings concerning the cause, frequency, evolution, and work-up of conditions manifesting as AHCE and normal or abnormal electromyography (EMG) respectively muscle biopsy. Systematic PubMed search. There are numerous primary (hereditary) and acquired myopathies that manifest with permanent, recurrent, or temporary AHCE with/without myopathic EMG or muscle biopsy. AHCE particularly occurs at onset of these conditions, which include dystrophinopathies, myotilinopathies, calpainopathy, caveolinopathy, dysferlinopathy, central core disease, multicore disease, desminopathy, MD1, MD2, hypoPP, malignant hyperthermia susceptibility, Pompe disease, McArdle disease, myoadenylate deaminase-deficiency, CPT2-deficiency, mitochondrial disorders, or myopathy with tubular aggregates. Most likely, other primary myopathies manifest with AHCE as well, without having been reported. Patients with AHCE should be taken seriously and repeated CK determination must be conducted. If hyper-CKemia is persisting or recurrent, these patients should undergo an EMG and eventually muscle biopsy. If noninformative, genetic work-up by a panel or whole exome sequencing should be initiated, irrespective of the family history. Patients with AHCE should avoid excessive exercise, require sufficient hydration, require counseling with regard to the risk of malignant hyperthermia, and should inform anesthesiologists and surgeons about their condition before elective surgery. Recurrent AHCE should be taken seriously and managed with conventional work-up. If noninformative, genetic work-up should follow irrespective of the family history.

Characterization of mesoangioblast cell fate and improved promyogenic potential of a satellite cell-like subpopulation upon transplantation in dystrophic murine muscles.

Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease caused by the lack of dystrophin in muscle fibersthat is currently without curative treatment. Mesoangioblasts (MABs) are multipotent progenitor cells that can differentiate to a myogenic lineage and that can be used to express Dystrophin upon transplantation into muscles, in autologous gene therapy approaches. However, their fate in the muscle environment remains poorly characterized. Here, we investigated the differentiation fate of MABs following their transplantation in DMD murine muscles using a mass cytometry strategy. This allowed the identification and isolation of a fraction of MAB-derived cells presenting common properties with satellite muscle stem cells. This analysis also indicated that most cells did not undergo a myogenic differentiation path once in the muscle environment, limiting their capacity to restore dystrophin expression in transplanted muscles. We therefore assessed whether MAB treatment with cytokines and growth factors prior to engraftment may improve their myogenic fate. We identified a combination of such signals that ameliorates MABs capacity to undergo myogenic differentiation in vivo and to restore dystrophin expression upon engraftment in myopathic murine muscles.