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Tissue Engineering. Part B, Reviews Oct 2014Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease.... (Review)
Review
Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.
Topics: Cell Differentiation; Coculture Techniques; Humans; Muscle Fibers, Skeletal; Myoblasts; Tissue Engineering
PubMed: 24320971
DOI: 10.1089/ten.TEB.2013.0534 -
Annals of Anatomy = Anatomischer... May 2015Bone density and quantity are primary conditions for the insertion and stability of dental implants. In cases of a lack of adequate maxillary or mandibulary bone, bone... (Review)
Review
Bone density and quantity are primary conditions for the insertion and stability of dental implants. In cases of a lack of adequate maxillary or mandibulary bone, bone augmentation will be necessary. The use of synthetic bioactive bone substitution materials is of increasing importance as alternatives to autogenously bone grafts. It is well known that bone can influence muscle function and muscle function can influence bone structures. Muscles have a considerable potential of adaptation and muscle tissue surrounding an inserted implant or bone surrogate can integrate changes in mechanical load of the muscle and hereupon induce signaling cascades with protein synthesis and arrangement of the cytoskeleton. The Musculus latissimus dorsi is very often used for the analyses of the in vivo biocompatibility of newly designed biomaterials. Beside macroscopically and histologically examination, biocompatibility can be assessed by analyses of the biomaterial influence of gene expression. This review discusses changes in the fiber type distribution, myosin heavy chain isoform composition, histological appearance and vascularization of the skeletal muscle after implantation of bone substitution materials. Especially, the effects of bone surrogates should be described at the molecular-biological and cellular level.
Topics: Biocompatible Materials; Bone Substitutes; Choristoma; Humans; Intercellular Signaling Peptides and Proteins; Materials Testing; Muscle, Skeletal; Prostheses and Implants; Skeletal Muscle Myosins
PubMed: 25159858
DOI: 10.1016/j.aanat.2014.07.008 -
Journal of Tissue Engineering and... Dec 2022Skeletal muscle tissue engineering has been a key area of focus over the years and has been of interest for developing regenerative strategies for injured or... (Review)
Review
Skeletal muscle tissue engineering has been a key area of focus over the years and has been of interest for developing regenerative strategies for injured or degenerative skeletal muscle tissue. Stem cells have gained increased attention as sources for developing skeletal muscle tissue for subsequent studies or potential treatments. Focus has been placed on understanding the molecular pathways that govern skeletal muscle formation in development to advance differentiation of stem cells towards skeletal muscle fates in vitro. Use of growth factors and transcription factors have long been the method for guiding skeletal muscle differentiation in vitro. However, further research in small molecule induced differentiation offers a xeno-free option that could result from use of animal derived factors.
Topics: Animals; Tissue Engineering; Muscle Development; Muscle, Skeletal; Stem Cells; Cell Differentiation; Satellite Cells, Skeletal Muscle
PubMed: 36223074
DOI: 10.1002/term.3355 -
Biofabrication Jun 2019Skeletal muscle is a tissue with a complex and hierarchical architecture that influences its functional properties. In order to exert its contractile function, muscle... (Review)
Review
Skeletal muscle is a tissue with a complex and hierarchical architecture that influences its functional properties. In order to exert its contractile function, muscle tissue is connected to neural, vascular and connective compartments, comprising finely structured interfaces which are orchestrated by multiple signalling pathways. Pathological conditions such as dystrophies and trauma, or physiological situations such as exercise and aging, modify the architectural organization of these structures, hence affecting muscle functionality. To overcome current limitations of in vivo and standard in vitro models, microfluidics and biofabrication techniques have been applied to better reproduce the microarchitecture and physicochemical environment of human skeletal muscle tissue. In the present review, we aim to critically discuss the role of those techniques, taken individually or in combination, in the generation of models that mimic the complex interfaces between muscle tissue and neural/vascular/tendon compartments. The exploitation of either microfluidics or biofabrication to model different muscle interfaces has led to the development of constructs with an improved spatial organization, thus presenting a better functionality as compared to standard models. However, the achievement of models replicating muscle-tissue interfaces with adequate architecture, presence of fundamental proteins and recapitulation of signalling pathways is still far from being achieved. Increased integration between microfluidics and biofabrication, providing the possibility to pattern cells in predetermined structures with higher resolution, will help to reproduce the hierarchical and heterogeneous structure of skeletal muscle interfaces. Such strategies will further improve the functionality of these techniques, providing a key contribution towards the study of skeletal muscle functions in physiology and pathology.
Topics: Animals; Humans; Microtechnology; Models, Biological; Muscle, Skeletal; Tendons; Tissue Engineering
PubMed: 31042682
DOI: 10.1088/1758-5090/ab1e7c -
Journal of Applied Physiology... Oct 2021The purpose of this project was to provide a profile of DNA, RNA, and protein content in adipose tissue, which is relatively understudied in humans, to gain more insight...
The purpose of this project was to provide a profile of DNA, RNA, and protein content in adipose tissue, which is relatively understudied in humans, to gain more insight into the amount of tissue that may be required for various analyses. Skeletal muscle tissue was also investigated to provide a direct comparison into potential differences between these two highly metabolically active tissues. Basal adipose and skeletal muscle tissue samples were obtained from 10 (7 M, 3 W) recreationally active participants [25 ± 1 yr; 84 ± 3 kg, maximal oxygen consumption (V̇o): 3.5 ± 0.2 L/min, body fat: 29 ± 2%]. DNA, RNA, and protein were extracted and subsequently analyzed for quantity and quality. DNA content of adipose and skeletal muscle tissue was 52 ± 14 and 189 ± 44 ng DNA·mg tissue, respectively ( < 0.05). RNA content of adipose and skeletal muscle tissue was 46 ± 14 and 537 ± 72 ng RNA·mg tissue, respectively ( < 0.05). Protein content of adipose and skeletal muscle tissue was 4 ± 1 and 177 ± 10 µg protein·mg tissue, respectively ( < 0.05). In summary, human adipose had 28% of the DNA, 9% of the RNA, and 2% of the protein found in skeletal muscle per mg of tissue. This information should be useful across a wide range of human clinical investigation designs and various laboratory analyses. This investigation studied DNA, RNA, and protein contents of adipose and skeletal muscle tissues from young active individuals. A series of optimization steps were investigated to aid in determining the optimal approach to extract high-yield and high-quality biomolecules. These findings contribute to the knowledge gap in adipose tissue requirements for molecular biology assays, which is of increasing importance due to the growing interest in adipose tissue research involving human exercise physiology research.
Topics: Adipose Tissue; DNA; Exercise; Humans; Muscle, Skeletal; RNA
PubMed: 34435508
DOI: 10.1152/japplphysiol.00343.2021 -
Cells, Tissues, Organs 2016Tissue-engineered skeletal muscle holds promise as a source of graft tissue for repair of volumetric muscle loss and as a model system for pharmaceutical testing. To... (Review)
Review
Tissue-engineered skeletal muscle holds promise as a source of graft tissue for repair of volumetric muscle loss and as a model system for pharmaceutical testing. To reach this potential, engineered tissues must advance past the neonatal phenotype that characterizes the current state of the art. In this review, we describe native skeletal muscle development and identify important growth factors controlling this process. By comparing in vivo myogenesis to in vitro satellite cell cultures and tissue engineering approaches, several key similarities and differences that may potentially advance tissue-engineered skeletal muscle were identified. In particular, hepatocyte and fibroblast growth factors used to accelerate satellite cell activation and proliferation, followed by addition of insulin-like growth factor as a potent inducer of differentiation, are proven methods for increased myogenesis in engineered muscle. Additionally, we review our recent novel application of dexamethasone (DEX), a glucocorticoid that stimulates myoblast differentiation, in skeletal muscle tissue engineering. Using our established skeletal muscle unit (SMU) fabrication protocol, timing- and dose-dependent effects of DEX were measured. The supplemented SMUs demonstrated advanced sarcomeric structure and significantly increased myotube diameter and myotube fusion compared to untreated controls. Most significantly, these SMUs exhibited a fivefold rise in force production. Thus, we concluded that DEX may serve to improve myogenesis, advance muscle structure, and increase force production in engineered skeletal muscle.
Topics: Animals; Humans; Intercellular Signaling Peptides and Proteins; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Tissue Engineering
PubMed: 27825154
DOI: 10.1159/000444671 -
Science (New York, N.Y.) Mar 2019
Topics: Humans; In Vitro Techniques; Models, Biological; Muscle, Skeletal; Regeneration; Regenerative Medicine; Tissue Engineering
PubMed: 30846593
DOI: 10.1126/science.aaw3611 -
Current Topics in Developmental Biology 2024The proper functioning of skeletal muscles is essential throughout life. A crucial crosstalk between the environment and several cellular mechanisms allows striated... (Review)
Review
The proper functioning of skeletal muscles is essential throughout life. A crucial crosstalk between the environment and several cellular mechanisms allows striated muscles to perform successfully. Notably, the skeletal muscle tissue reacts to an injury producing a completely functioning tissue. The muscle's robust regenerative capacity relies on the fine coordination between muscle stem cells (MuSCs or "satellite cells") and their specific microenvironment that dictates stem cells' activation, differentiation, and self-renewal. Critical for the muscle stem cell pool is a fine regulation of chromatin organization and gene expression. Acquiring a lineage-specific 3D genome architecture constitutes a crucial modulator of muscle stem cell function during development, in the adult stage, in physiological and pathological conditions. The context-dependent relationship between genome structure, such as accessibility and chromatin compartmentalization, and their functional effects will be analysed considering the improved 3D epigenome knowledge, underlining the intimate liaison between environmental encounters and epigenetics.
Topics: Chromatin; Animals; Humans; Muscle, Skeletal; Cell Differentiation; Stem Cells; Epigenesis, Genetic; Muscle Development; Satellite Cells, Skeletal Muscle
PubMed: 38670713
DOI: 10.1016/bs.ctdb.2024.01.014 -
Biology Direct Jul 2023Volumetric Muscle Loss (VML), resulting from severe trauma or surgical ablation, is a pathological condition preventing myofibers regeneration, since skeletal muscle...
BACKGROUND
Volumetric Muscle Loss (VML), resulting from severe trauma or surgical ablation, is a pathological condition preventing myofibers regeneration, since skeletal muscle owns the remarkable ability to restore tissue damage, but only when limited in size. The current surgical therapies employed in the treatment of this pathology, which particularly affects military personnel, do not yet provide satisfactory results. For this reason, more innovative approaches must be sought, specifically skeletal muscle tissue engineering seems to highlight promising results obtained from preclinical studies in VML mouse model. Despite the great results obtained in rodents, translation into human needs a comparable animal model in terms of size, in order to validate the efficacy of the tissue engineering approach reconstructing larger muscle mass (human-like). In this work we aim to demonstrate the validity of a porcine model, that has underwent a surgical ablation of a large muscle area, as a VML damage model.
RESULTS
For this purpose, morphological, ultrasound, histological and fluorescence analyses were carried out on the scar tissue formed following the surgical ablation of the peroneus tertius muscle of Sus scrofa domesticus commonly called mini-pig. In particular, the replenishment of the damaged area, the macrophage infiltration and the vascularization at different time-points were evaluated up to the harvesting of the scar upon six months.
CONCLUSION
Here we demonstrated that following VML damage, there is an extremely poor regenerative process in the swine muscle tissue, while the formation of fibrotic, scar tissue occurs. The analyses performed up to 180 days after the injury revealed the development of a stable, structured and cellularized tissue, provided with vessels and extracellular matrix acquiring the status of granulation tissue like in human.
Topics: Humans; Mice; Animals; Swine; Cicatrix; Longitudinal Studies; Swine, Miniature; Muscle, Skeletal; Muscular Diseases
PubMed: 37518063
DOI: 10.1186/s13062-023-00399-1 -
Current Topics in Developmental Biology 2018Satellite cells, adult stem cells in skeletal muscle tissue, reside within a mechanically dynamic three-dimensional microenvironment. With each contraction-relaxation... (Review)
Review
Satellite cells, adult stem cells in skeletal muscle tissue, reside within a mechanically dynamic three-dimensional microenvironment. With each contraction-relaxation cycle, a satellite cell is expected to experience tensile, shear, and compressive stresses, and through cell-extracellular matrix interactions, also gauge the stiffness of the niche. Via mechanoreceptors, cells can sense these biophysical parameters of the niche, which serve to physically induce conformational changes that impact biomolecule activity, and thereby alter downstream signal transduction pathways and ultimately cell fate. An emerging body of literature supports the notion that myogenic cells, too, integrate biochemical factors together with biomechanical stresses and that this may serve to provide spatio-temporal control of cell fate in the complicated three-dimensional niche. Further, skeletal muscle regenerative medicine therapies are being improved by applying this fresh insight. In this focused chapter, the progression of skeletal muscle regeneration is dissected into a dynamic conversation between muscle progenitor cells and the mechanical properties of the extracellular matrix. The significance of biophysical regulation to myogenic repair is reinforced by the exaggerative influences of extrinsic mechanical stresses and the pathological implications of ECM dysregulation. Additional fundamental studies that further define the satellite cell biophysical environment in health, regeneration, aging, and disease may serve to close knowledge gaps and bolster skeletal muscle regenerative medicine.
Topics: Adult Stem Cells; Animals; Humans; Mechanotransduction, Cellular; Models, Biological; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle
PubMed: 29304997
DOI: 10.1016/bs.ctdb.2017.08.007