Metabolic Therapies for Muscle Injury
Kohlstadt Ingrid, Cintron Kenneth in Metabolic Therapies in Orthopedics, Second Edition, 2018
Research has been focused on muscle satellite cells (SC) and their role in muscle repair and regeneration. They are skeletal muscle mononuclear stem cells, which remain in a quiescent state until activation occurs in response to different physiological and pathological stimuli, including exercise, stretching, electrical stimulation and injury such as post-training micro-injuries [77]. Activation results in the formation of precursor myogenic cells known as myoblasts, which are responsible for muscle fiber hypertrophy through the addition of nuclei to existing myofibers [18]. They also have an important implication in cell therapy due to their self-renewal as well as their capability to differentiate into myofibers, processes which depend on a number of factors, including the microenvironment and the presence of myogenic regulatory factors.
Skeletal Muscle
Manoj Ramachandran, Tom Nunn in Basic Orthopaedic Sciences, 2018
Skeletal muscle cells are of mesodermal origin. Mature cells are known as myotubes or muscle fibres. They are differentiated multinucleated cells formed by cytoplasmic fusion of immature mononucleated myoblasts. In muscle growth, these mononucleated precursor cells also fuse to the myotubes, adding to both the ends and the side of the cell. Muscle fibres vary in size and length between the sexes and between muscle groups. Individual fibres span the full length of the muscle they form. Fibres in muscles that have a precision requirement, such as the small muscles of the hand, tend to be smaller than in power muscles, such as the quadriceps, reflecting their contractile protein content. The fibre size is also related intimately to the innervation of the muscle, further illustrating the link between fibre size and function. Muscle fibres are bounded by a plasma membrane, the sarcolemma, and have a cytoplasm termed the sarcoplasm.
Proto-Oncogene and Onco-Suppressor Gene Expression
Enrique Pimentel in Handbook of Growth Factors, 2017
The c-myc proto-oncogene may have an important role in some developmental processes. Two distinct c-myc genes (c-myc-I and c-myc-II) are contained in the genome of Xenopus laevis, and they are differentially regulated during developmental processes occurring in this amphibian species, with one c-myc gene active in oocytes and the other active in both oocytes and postgastrula embryos.626 Expression of the c-Myc protein may play an important role in the differentiation of specific organs and tissues in other vertebrates. Selected examples are mentioned in the following. Explants of the central region of embryonic chicken lens epithelia can be induced to differentiate into lens fiber cells when cultured in the presence of fetal calf serum, insulin, IGF, or vitreous humor (which contains IGF). The levels of c-myc transcripts are transiently elevated in the differentiating lens epithelial explants in the absence of mitogenic stimulation, as the cells withdraw from the cell cycle.627 Differentiation of SHE myoblasts in vitro is associated with enhanced expression of the c-myc gene.628 Myc proteins can induce the expression of a differentiated phenotype in quail neural crest cells, with the appearance of catecholaminergic traits.629 The Myc protein has been detected in mature mammalian sperm cells, including human sperm cells, and it may have a role in sperm cell function, especially in capacitation and/or acrosome reaction.630
Stem cell therapy for acute myocardial infarction: MSCs and iPscs
Published in Expert Opinion on Biological Therapy, 2023
Diana Clavellina, Wayne Balkan, Joshua M Hare
Skeletal myoblasts were used in pioneer preclinical and clinical trials in CRM. Skeletal muscle contains an intrinsic reserve of tissue-committed cells able to proliferate, differentiate and merge with existing myocytes to regenerate the muscle when recruited to the injured tissue. The initial excitement toward these cells was motivated by their high culture scalability, immune safety, and strong resistance under ischemic conditions. However, skeletal myoblasts are also characterized by lineage restriction, which limits their potential to differentiate into new cardiomyocytes [25]. Early studies of these cells also reported an increased risk of arrhythmias attributed to the limited cell electrical synchronization activity. with the native myocardial cells [26]. Findings from the Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial demonstrated the safety of skeletal myoblasts. Interestingly, the MAGIC trial provided evidence supporting the concept that transferred skeletal myoblasts convey a therapeutic paracrine significance in the short term rather than any long-term structural value [27].
Muscle regeneration after high-dose radiation exposure: therapeutic potential of Hedgehog pathway modulation?
Published in International Journal of Radiation Biology, 2022
E. Rota Graziosi, S. François, J. Pateux, M. Gauthier, X. Butigieg, M. Oger, M. Drouet, D. Riccobono, N. Jullien
Muscle repair is a complex process that involves the regeneration of damaged fibers by new ones formed from particular stem cells identified in 1961 by Mauro and known as satellite cells (SC) (Mauro 1961; Zammit et al. 2006). These progenitors, interspersed between the plasma membrane and the basal layer of fibers, can be activated from their quiescent state following a traumatic event to proliferate and differentiate into mature myoblasts, which fuze to reconstitute myotubes. These newly-formed structures merge into myofibers and regenerate a functional muscle. The different stages of differentiation, fusion and maturation are orchestrated by a cascade of myogenic regulatory factors (MRF). SC markers Pax3 and Pax7 disappear after the early stages of activation. Then, in the intermediate stages, Myf5 and MyoD are necessary for myoblast commitment toward muscle cell differentiation. Myogenin (MyoG gene) plays a role in the late phases of fusion and in the synthesis of Myosin, essential for muscle functionality (Hawke and Garry 2001). Other mature proteins are also synthesized at the end of the process, such as beta-enolase (ENO3 gene) which is involved especially in the storage of glycogen.
Effect of sub-toxic exposure to Malathion on glucose uptake and insulin signaling in L6 myoblast derived myotubes
Published in Drug and Chemical Toxicology, 2020
Shrijana Shrestha, Vijay Kumar Singh, Sajib Kumar Sarkar, Balasubramanian Shanmugasundaram, Kadirvelu Jeevaratnam, Bidhan Chandra Koner
Rat myoblast (L6) cell line was obtained from the National Centre for Cell Sciences (Pune, India) and propagated at 37 °C in 5% CO2 in DMEM supplemented with 100 units/ml of penicillin G, 100 μg/ml of streptomycin sulfate, 100 μg/ml amphotericin B and 10% FBS. Once the myoblasts reached 70–80% confluence, the L6 myoblasts were allowed to differentiate spontaneously into myotubes for 5–7 days in differentiation medium (DMEM supplemented with 100 units/ml penicillin, 100 μg/ml of streptomycin sulfate, 100 μg/ml amphotericin B and 2% FBS). The differentiation of myoblasts into myotubes was checked by the morphology and fusion of myotubes under the microscope. All the following experiments were carried out in the differentiated myotubes. For assay of insulin signaling, RSK, antioxidant and TNFα, cells were grown in 75 cm2 culture flasks. For glucose uptake and MTT assay, it was done in 96 well microtitre plates (Tarsons India Pvt. Ltd., Kolkata, India).
Related Knowledge Centers
- Calcium
- Cell Proliferation
- Fibroblast Growth Factor
- Multinucleate
- Embryo
- Cellular Differentiation
- Skeletal Muscle
- Animal Embryonic Development
- Precursor Cell
- Cell Fusion