Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 16(1)
Published: Dec. 26, 2024
Language: Английский
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 10, 2025
Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck current therapeutic strategies for muscular dystrophies, as it precludes the possibility promoting compensatory regeneration. Here we describe muscle-targeting delivery platform, based on gold nanoparticles, that enables release oligonucleotides into MuSCs. We demonstrate AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic microRNA-206 MuSCs, thereby regeneration and improving functionality, in mouse model Duchenne Muscular Dystrophy. show here this platform is biocompatible, non-toxic, non-immunogenic, can be easily adapted wide range diseased muscles. Lack cell limits treatment dystrophies. Here, authors functionalized nanoparticles allows selective promotes skeletal
Language: Английский
Citations
5
Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12
Published: Jan. 6, 2025
Muscle repair and regeneration are complex processes. In Duchenne muscular dystrophy (DMD), these processes disrupted by the loss of functional dystrophin, a key part transmembrane dystrophin-associated glycoprotein that stabilizes myofibers, indirectly leading to progressive muscle wasting, subsequent ambulation, respiratory cardiac insufficiency, premature death. As DMD pathology, histone deacetylase (HDAC) activity is constitutively increased, epigenetic changes inhibition factors, chronic inflammation, fibrosis, adipogenesis. HDAC has consequently been investigated as therapeutic approach for dystrophies that, significantly, works independently from specific genetic mutations, making it potentially suitable all patients with DMD. This review discusses how addresses pathophysiology in multi-targeted mode action summarizes recent evidence on rationale givinostat, which now approved United States Food Drug Administration treatment aged 6 years older.
Language: Английский
Citations
2
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 512 - 512
Published: Dec. 29, 2023
Skeletal muscle regeneration is a complex process involving the generation of new myofibers after trauma, competitive physical activity, or disease. In this context, adult skeletal stem cells, also known as satellite cells (SCs), play crucial role in regulating tissue homeostasis and activating regeneration. Alterations their number function have been associated with various pathological conditions. The main factors involved dysregulation SCs' activity are inflammation, oxidative stress, fibrosis. This review critically summarizes current knowledge on SCs It examines changes three most common severe disorders: sarcopenia, muscular dystrophy, cancer cachexia. Understanding molecular mechanisms dysregulations essential for improving treatments, such exercise, developing personalized approaches to reactivate SCs.
Language: Английский
Citations
16
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Abstract Duchenne muscular dystrophy (DMD) patients suffer from skeletal and cardiopulmonary weakness, interestingly up to one third are diagnosed on the autism spectrum. Dystrophin is an essential protein for regulating transmission of intracellular force extracellular matrix within muscle, but also plays key roles in neurobehavior cognitive function. The mouse dystrophin gene (also abbreviated Dmd ) X-linked has several isoforms with tissue-specific expression, including large Dp427m muscle transcript found heart Dp427c that encodes brain-specific cerebellar protein. Understanding functional requirements pathways affected by loss will impact replacement therapy exon-skipping correction strategies. We generated conditional knockout mice targeting exon 52 ( flox52 locus. constitutive inducible myofiber mKO) evaluate function isoform. Constitutive embryonic deletion exclusively myofibers resulted a severe myopathy, dystrophic histopathology, deficits compared mdx mouse. Transcriptomic analysis mKO revealed dysregulation cytokine signaling pathways. Separately, we Purkinje neuron :Pcp2 KO) displayed neurobehavioral social approach, memory, spatial navigation working memory. These studies reveal requirement expression both brain normal physiological Significance Statement caused lack muscle. (Dp427m) isoform expressed skeletal, cardiac, smooth its remain unknown. characterized mKO). genetic ablation histopathologies similar mouse, while postnatal milder pathologies. Ablating using Pcp2/L7 -Cre driver sociobehavioral defects. showed reduction Our study reveals role identifies modulation dystrophin-replacement therapies.
Language: Английский
Citations
0
Russian Journal of Archive of Pathology, Journal Year: 2025, Volume and Issue: 87(1), P. 28 - 28
Published: Feb. 12, 2025
Dysferlinopathy represents an orphan disease within the spectrum of progressive muscular dystrophies, occurring at a frequency 1 to 9 cases per 1.000.000 individuals (Orphanet, 2024). It arises from mutations in DYSF gene (OMIM 603009, 2p13, NM_003494.4), which is responsible for coding transmembrane protein dysferlin. Dysferlin plays critical role repair muscle fiber membranes and cellular processes skeletal regeneration. Although molecular mechanisms dysferlin-mediated are under active investigation, reports on ultrastructural alterations human muscles due dysferlin deficiency sparse. Objective. To identify pathomorphological features 6 patients with dysferlinopathy. Material methods. This study presents pathomorphological, immunohistochemical, data biopsies molecularly confirmed Results. Examination paraffin-embedded sections anterior tibialis vastus lateralis muscles, stained hematoxylin eosin, identified primarily myopathic pattern injury. Immunohistochemical staining antibodies revealed absence tissue compared positive control. Transmission electron microscopy has characteristic dysferlinopathy, although not specific, including thickening fragmentation basal membrane, thinning lysis myofibrils, folding disruptions sarcolemma, destruction mitochondria, and, newly described this disease, necrosis myosatellite cells telocytes muscles. Conclusion. Despite non-specificity alterations, dysferlinopathy can provide additional information about underlying development. The finding cell telocyte indicates impairment regenerative capacity, may be novel link pathogenesis
Language: Английский
Citations
0
Small Methods, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 18, 2025
Abstract Muscle regeneration is a vital biological process that crucial for maintaining muscle function and integrity, particularly the treatment of diseases such as sarcopenia muscular dystrophy. Generally, tissues can self‐repair regenerate under various conditions, including acute or chronic injuries, aging, genetic mutation. However, becomes challenging beyond certain threshold, in severe injuries progressive diseases. In recent years, liposome‐based nanotechnologies have shown potential promising therapeutic strategies regeneration. Liposomes offer an adaptable platform targeted drug delivery due to their cell membrane‐like structure excellent biocompatibility. They enhance solubility, stability, while minimizing systemic side effects by different mechanisms. This review summarizes advancements, discusses current applications mechanisms, highlights challenges future directions possible clinical translation nanomaterials It hoped this offers new insights into development liposome‐enabled nanomedicine address limitations.
Language: Английский
Citations
0
Current Treatment Options in Neurology, Journal Year: 2025, Volume and Issue: 27(1)
Published: April 15, 2025
Language: Английский
Citations
0
Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1109 - 1109
Published: May 3, 2025
Background: Three-dimensional skeletal muscle organoids (3D SkMO) are becoming of increasing interest for preclinical studies in Duchenne muscular dystrophy (DMD), provided that the used platform demonstrates possibility to form functional and reproducible 3D SkMOs, investigate on potential patient-related phenotypic differences. Methods: In this study, we employed fibrin-based derived from immortalized myogenic precursors DMD patients carrying either a stop codon mutation exon 59 or 48–50 deletion. We compared dystrophic lines with healthy wild-type control (HWT) by assessing microtissue formation ability, contractile function at multiple timepoints along intracellular calcium dynamics via imaging, as well expression markers. Results: found patient-specific structural differences early stages SkMO development. Contractile force, measured both single twitch tetanic responses, was significantly lower SkMOs HWT, most pronounced observed day 7 differentiation. However, these disparities diminished over time under similar culturing conditions absence continuous nerve-like stimulation, suggesting primary deficit lies delayed maturation, also supported gene analysis. Conclusions: Our results underline that, despite initial maturation delay, retain capacity once intrinsic lag is overcome. This suggests critical role dystrophin development, while contraction-induced stress and/or an inflammatory microenvironment essential fully recapitulate phenotypes SkMOs.
Language: Английский
Citations
0
European Journal of Translational Myology, Journal Year: 2023, Volume and Issue: unknown
Published: Oct. 16, 2023
Duchenne muscular dystrophy is a highly progressive muscle wasting disease of early childhood and characterized by complex pathophysiological histopathological changes in the voluntary contractile system, including myonecrosis, chronic inflammation, fat substitution reactive myofibrosis. The continued loss functional myofibres replacement with non-contractile cells, as well extensive tissue scarring decline elasticity, leads to severe skeletal weakness. In addition, dystrophic muscles exhibit greatly diminished regenerative capacity counteract ongoing process fibre degeneration. normal tissues, an abundant stem cell pool consisting satellite cells that are localized between sarcolemma basal lamina, provides rich source for production activated myogenic progenitor involved efficient myofibre repair regeneration. Interestingly, self-renewal maintaining essential matured increased dystrophin-deficient fibres. However, hyperplasia does not result recovery due impaired asymmetric divisions. lack expression full-length dystrophin isoform Dp427-M, which primary defects DMD gene, appears affect key regulators polarity causing reduced differentiation progenitors, This review outlines complexity dystrophinopathy describes importance role dysfunction. A brief discussion bioanalytical usefulness single proteomics future studies biology provided.
Language: Английский
Citations
6
Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(7), P. 1981 - 1994
Published: July 13, 2024
Stem cell therapy holds significant potential for skeletal muscle repair, with in vitro-generated human reserve cells (MuRCs) emerging as a source of quiescent myogenic stem that can be injected to enhance regeneration. However, the clinical translation such therapies is hampered by need fetal bovine serum (FBS) during vitro generation MuRCs. This study aimed determine whether fresh allogeneic platelet-rich plasma (PRP) combined or not hyaluronic acid (PRP-HA) could effectively replace xenogeneic FBS ex vivo expansion and differentiation primary myoblasts. Cells were cultured media supplemented either PRP PRP-HA their proliferation rate, cytotoxicity compared those FBS. The results showed similar rates among myoblasts PRP, media, no cytotoxic effects. Human reduced fusion ability upon differentiation. Nevertheless, we also observed MuRCs generated from cultures, exhibited increased Pax7 expression delayed re-entry into cycle reactivation, indicating deeper state These suggest replaces favors
Language: Английский
Citations
1