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Journal of Cachexia, Sarcopenia and... Feb 2022Recent advances in the transcriptomics, translatomics, and proteomics have led us to the exciting new world of functional endogenous microproteins. These microproteins... (Review)
Review
Recent advances in the transcriptomics, translatomics, and proteomics have led us to the exciting new world of functional endogenous microproteins. These microproteins have a small size and are derived from small open reading frames (smORFs) of RNAs previously annotated as non-coding (e.g. lncRNAs and circRNAs) as well as from untranslated regions and canonical mRNAs. The presence of these microproteins reveals a much larger translatable portion of the genome, shifting previously defined dogmas and paradigms. These findings affect our view of organisms as a whole, including skeletal muscle tissue. Emerging evidence demonstrates that several smORF-derived microproteins play crucial roles during muscle development (myogenesis), maintenance, and regeneration, as well as lipid and glucose metabolism and skeletal muscle bioenergetics. These microproteins are also involved in processes including physical activity capacity, cellular stress, and muscular-related diseases (i.e. myopathy, cachexia, atrophy, and muscle wasting). Given the role of these small proteins as important key regulators of several skeletal muscle processes, there are rich prospects for the discovery of new microproteins and possible therapies using synthetic microproteins.
Topics: Muscle, Skeletal; Open Reading Frames; Proteins; RNA, Messenger; Transcriptome
PubMed: 34850602
DOI: 10.1002/jcsm.12866 -
Current Gene Therapy 2015Satellite cells are unipotent stem cells involved in muscle regeneration. However, the skeletal muscle microenvironment exerts a dominant influence over stem cell... (Review)
Review
Satellite cells are unipotent stem cells involved in muscle regeneration. However, the skeletal muscle microenvironment exerts a dominant influence over stem cell function. The cell intrinsic complexity of the skeletal muscle niche located within the connective tissue between fibers includes motor neurons, tendons, blood vessels, immune response mediators and interstitial cells. All these cell types modulate the trafficking of stimuli responsible of muscle fiber regeneration. In addition, several stem cell types have been discovered in skeletal muscle tissue, mainly located in the interstitium. The majority of these stem cells appears to directly contribute to myogenic differentiation, although some of them are mainly implicated in paracrine effects. This review focuses on adult stem cells, which have been used for therapeutic purposes, mainly in animal models of chronic muscle degeneration. Emerging literature identifies other myogenic progenitors generated from pluripotent stem cells as potential candidates for the treatment of skeletal muscle degeneration. However, adult stem cells still represent the gold standard for future comparative studies.
Topics: Adult Stem Cells; Animals; Disease Models, Animal; Exosomes; Gene Expression Regulation; Humans; MicroRNAs; Muscle, Skeletal; Muscular Dystrophies; Regeneration; Stem Cell Transplantation
PubMed: 26122100
DOI: 10.2174/1566523215666150630121024 -
Advances in Experimental Medicine and... 2019The muscular dystrophies are an heterogeneous group of inherited myopathies characterised by the progressive wasting of skeletal muscle tissue. Pericytes have been shown...
The muscular dystrophies are an heterogeneous group of inherited myopathies characterised by the progressive wasting of skeletal muscle tissue. Pericytes have been shown to make muscle in vitro and to contribute to skeletal muscle regeneration in several animal models, although recent data has shown this to be controversial. In fact, some pericyte subpopulations have been shown to contribute to fibrosis and adipose deposition in muscle. In this chapter, we explore the identity and the multifaceted role of pericytes in dystrophic muscle, potential therapeutic applications and the current need to overcome the hurdles of characterisation (both to identify pericyte subpopulations and track cell fate), to prevent deleterious differentiation towards myogenic-inhibiting subpopulations, and to improve cell proliferation and engraftment efficacy.
Topics: Animals; Cell Differentiation; Muscle Development; Muscle, Skeletal; Muscular Dystrophies; Pericytes; Regeneration
PubMed: 31147885
DOI: 10.1007/978-3-030-16908-4_15 -
International Journal of Molecular... Oct 2021In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and... (Review)
Review
In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and innate immune responses. However, the exact mechanisms behind muscle tissue regeneration, homeostasis, and plasticity are still under investigation, and the discovery of pathways and cell types involved in muscle repair can open the way for novel therapeutic approaches, such as cell-based therapies involving stem cells and peripheral blood mononucleate cells. Indeed, peripheral cell infusions are a new therapy for muscle healing, likely because autologous peripheral blood infusion at the site of injury might enhance innate immune responses, especially those driven by macrophages. In this review, we summarize current knowledge on functions of stem cells and macrophages in skeletal muscle repairs and their roles as components of a promising cell-based therapies for muscle repair and regeneration.
Topics: Animals; Humans; Immunity, Innate; Macrophages; Muscle, Skeletal; Muscular Diseases; Regenerative Medicine; Stem Cells
PubMed: 34639203
DOI: 10.3390/ijms221910867 -
Endocrinology and Metabolism (Seoul,... Jun 2022Skeletal muscle is now regarded as an endocrine organ based on its secretion of myokines and exerkines, which, in response to metabolic stimuli, regulate the crosstalk...
Skeletal muscle is now regarded as an endocrine organ based on its secretion of myokines and exerkines, which, in response to metabolic stimuli, regulate the crosstalk between the skeletal muscle and other metabolic organs in terms of systemic energy homeostasis. This conceptual basis of skeletal muscle as a metabolically active organ has provided insights into the potential role of physical inactivity and conditions altering muscle quality and quantity in the development of multiple metabolic disorders, including insulin resistance, obesity, and diabetes. Therefore, it is important to understand human muscle physiology more deeply in relation to the pathophysiology of metabolic diseases. Since monolayer cell lines or animal models used in conventional research differ from the pathophysiological features of the human body, there is increasing need for more physiologically relevant in vitro models of human skeletal muscle. Here, we introduce recent studies on in vitro models of human skeletal muscle generated from adult myogenic progenitors or pluripotent stem cells and summarize recent progress in the development of three-dimensional (3D) bioartificial muscle, which mimics the physiological complexity of native skeletal muscle tissue in terms of maturation and functionality. We then discuss the future of skeletal muscle 3D-organoid culture technology in the field of metabolic research for studying pathological mechanisms and developing personalized therapeutic strategies.
Topics: Animals; Cell Line; Homeostasis; Humans; Insulin Resistance; Muscle, Skeletal; Obesity
PubMed: 35798547
DOI: 10.3803/EnM.2022.302 -
Experimental Cell Research Jul 2022Engineering models of human skeletal muscle tissue provides unique translational opportunities to investigate and develop therapeutic strategies for acute muscle... (Review)
Review
Engineering models of human skeletal muscle tissue provides unique translational opportunities to investigate and develop therapeutic strategies for acute muscle injuries, and to establish personalised and precision medicine platforms for in vitro studies of severe neuromuscular and musculoskeletal disorders. Several myogenic and non-myogenic cell types can be isolated, generated, amplified and combined with scaffolds and biomaterials to achieve this aim. Novel bio-fabrication strategies, which include exogenous stimuli to enhance tissue maturation, promise to achieve an ever-increasing degree of tissue functionalisation both in vivo and in vitro. Here we review recent advances, current challenges and future perspectives to build human skeletal muscle tissue "in a dish", focusing on the cellular constituents and on applications for in vitro disease modelling. We also briefly discuss the impact that emerging technologies such as 3D bioprinting, organ-on-chip and organoids might have to circumvent technical hurdles in future studies.
Topics: Bioengineering; Bioprinting; Humans; Muscle, Skeletal; Tissue Engineering; Tissue Scaffolds
PubMed: 35427601
DOI: 10.1016/j.yexcr.2022.113133 -
Lab on a Chip Oct 2018A number of major disease states involve skeletal muscle, including type 2 diabetes, muscular dystrophy, sarcopenia and cachexia arising from cancer or heart disease.... (Review)
Review
A number of major disease states involve skeletal muscle, including type 2 diabetes, muscular dystrophy, sarcopenia and cachexia arising from cancer or heart disease. Animals do not accurately represent many of these disease states. Human skeletal muscle microphysiological systems derived from primary or induced pluripotent stem cells (hPSCs) can provide an in vitro model of genetic and chronic diseases and assess individual variations. Three-dimensional culture systems more accurately represent skeletal muscle function than do two-dimensional cultures. While muscle biopsies enable culture of primary muscle cells, hPSCs provide the opportunity to sample a wider population of donors. Recent advances to promote maturation of PSC-derived skeletal muscle provide an alternative to primary cells. While contractile function is often measured in three-dimensional cultures and several systems exist to characterize contraction of small numbers of muscle fibers, there is a need for functional measures of metabolism suited for microphysiological systems. Future research should address generation of well-differentiated hPSC-derived muscle cells, enabling muscle repair in vitro, and improved disease models.
Topics: Animals; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Muscle Contraction; Muscle, Skeletal; Tissue Engineering
PubMed: 30183050
DOI: 10.1039/c8lc00553b -
Methods (San Diego, Calif.) Apr 2016For over two decades, research groups have been developing methods to engineer three-dimensional skeletal muscle tissues. These tissues hold great promise for use in... (Review)
Review
For over two decades, research groups have been developing methods to engineer three-dimensional skeletal muscle tissues. These tissues hold great promise for use in disease modeling and pre-clinical drug development, and have potential to serve as therapeutic grafts for functional muscle repair. Recent advances in the field have resulted in the engineering of regenerative muscle constructs capable of survival, vascularization, and functional maturation in vivo as well as the first-time creation of functional human engineered muscles for screening of therapeutics in vitro. In this review, we will discuss the methodologies that have progressed work in the muscle tissue engineering field to its current state. The emphasis will be placed on the existing procedures to generate myogenic cell sources and form highly functional muscle tissues in vitro, techniques to monitor and evaluate muscle maturation and performance in vitro and in vivo, and surgical strategies to both create diseased environments and ensure implant survival and rapid integration into the host. Finally, we will suggest the most promising methodologies that will enable continued progress in the field.
Topics: Animals; Cell Culture Techniques; Cells, Cultured; Humans; Muscle, Skeletal; Regeneration; Regenerative Medicine; Satellite Cells, Skeletal Muscle; Stem Cell Niche; Tissue Engineering
PubMed: 26455485
DOI: 10.1016/j.ymeth.2015.10.002 -
Skeletal Muscle Feb 2020Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e., satellite cells, SCs), differentiated... (Review)
Review
Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e., satellite cells, SCs), differentiated cells (i.e., myofibers), and extracellular matrix cause a decline in tissue homeostasis, function, and regenerative capacity. Based on the conservation of aging across tissues and taking advantage of the relatively well-characterization of the myofibers and associated SCs, skeletal muscle emerged as an experimental system to study the decline in function and maintenance of old tissues and to explore rejuvenation strategies. In this review, we summarize the approaches for understanding the aging process and for assaying the success of rejuvenation that use skeletal muscle as the experimental system of choice. We further discuss (and exemplify with studies of skeletal muscle) how conflicting results might be due to variations in the techniques of stem cell isolation, differences in the assays of functional rejuvenation, or deciding on the numbers of replicates and experimental cohorts.
Topics: Aging; Animals; Cell Self Renewal; Humans; Muscle, Skeletal; Primary Cell Culture
PubMed: 32033591
DOI: 10.1186/s13395-020-0222-1 -
Journal of Cellular and Molecular... Jun 2019Both volumetric muscle loss (VML) and muscle degenerative diseases lead to an important decrease in skeletal muscle mass, condition that nowadays lacks an optimal... (Review)
Review
Both volumetric muscle loss (VML) and muscle degenerative diseases lead to an important decrease in skeletal muscle mass, condition that nowadays lacks an optimal treatment. This issue has driven towards an increasing interest in new strategies in tissue engineering, an emerging field that can offer very promising approaches. In addition, the discovery of induced pluripotent stem cells (iPSCs) has completely revolutionized the actual view of personalized medicine, and their utilization in skeletal muscle tissue engineering could, undoubtedly, add myriad benefits. In this review, we want to provide a general vision of the basic aspects to consider when engineering skeletal muscle tissue using iPSCs. Specifically, we will focus on the three main pillars of tissue engineering: the scaffold designing, the selection of the ideal cell source and the addition of factors that can enhance the resemblance with the native tissue.
Topics: Animals; Cell Culture Techniques; Cellular Reprogramming Techniques; Humans; Induced Pluripotent Stem Cells; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Muscle, Skeletal; Octamer Transcription Factor-3; Precision Medicine; Proto-Oncogene Proteins c-myc; Regeneration; SOXB1 Transcription Factors; Tissue Engineering; Tissue Scaffolds
PubMed: 30933431
DOI: 10.1111/jcmm.14292