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Nature Reviews. Immunology Mar 2017Diseases of muscle that are caused by pathological interactions between muscle and the immune system are devastating, but rare. However, muscle injuries that involve... (Review)
Review
Diseases of muscle that are caused by pathological interactions between muscle and the immune system are devastating, but rare. However, muscle injuries that involve trauma and regeneration are fairly common, and inflammation is a clear feature of the regenerative process. Investigations of the inflammatory response to muscle injury have now revealed that the apparently nonspecific inflammatory response to trauma is actually a complex and coordinated interaction between muscle and the immune system that determines the success or failure of tissue regeneration.
Topics: Animals; Humans; Muscle, Skeletal; Regeneration
PubMed: 28163303
DOI: 10.1038/nri.2016.150 -
Cell Reports Apr 2018Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D)...
Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development.
Topics: Cell Differentiation; Cell Lineage; Humans; Hydrogels; Induced Pluripotent Stem Cells; Models, Biological; Muscle Development; Muscle, Skeletal; Muscular Dystrophies; Tissue Engineering; Tissue Scaffolds
PubMed: 29669293
DOI: 10.1016/j.celrep.2018.03.091 -
Current Topics in Developmental Biology 2018Adult skeletal muscle is endowed with regenerative potential through partially recapitulating the embryonic developmental program. Upon acute injury or in pathological... (Review)
Review
Adult skeletal muscle is endowed with regenerative potential through partially recapitulating the embryonic developmental program. Upon acute injury or in pathological conditions, quiescent muscle-resident stem cells, called satellite cells, become activated and give rise to myogenic progenitors that massively proliferate, differentiate, and fuse to form new myofibers and restore tissue functionality. In addition, a proportion of activated cells returns back to quiescence and replenish the pool of satellite cells in order to maintain the ability of skeletal muscle tissue to repair. Self-renewal is the process by which stem cells divide to make more stem cells to maintain the stem cell population throughout life. This process is controlled by cell-intrinsic transcription factors regulated by cell-extrinsic signals from the niche and the microenvironment. This chapter provides an overview about the general aspects of satellite cell biology and focuses on the cellular and molecular aspects of satellite cell self-renewal. To date, we are still far from understanding how a very small proportion of the satellite cell progeny maintain their stem cell identity when most of their siblings progress through the myogenic program to construct myofibers.
Topics: Animals; Cell Differentiation; Cell Proliferation; Cell Self Renewal; Humans; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Wound Healing
PubMed: 29304998
DOI: 10.1016/bs.ctdb.2017.08.001 -
Journal of Strength and Conditioning... May 2020Gonzalez, AM and Trexler, ET. Effects of citrulline supplementation on exercise performance in humans: A review of the current literature. J Strength Cond Res 34(5):...
Gonzalez, AM and Trexler, ET. Effects of citrulline supplementation on exercise performance in humans: A review of the current literature. J Strength Cond Res 34(5): 1480-1495, 2020-L-citrulline, a nonessential amino acid found primarily in watermelon, has recently garnered much attention for its potential to augment L-arginine bioavailability, nitric oxide production, and exercise performance. Over the past decade, L-citrulline has received considerable scientific attention examining potentially ergogenic properties for both aerobic and anaerobic exercise performance. Thus, the purpose of this article is to summarize the theoretical rationale behind L-citrulline supplementation and to comprehensively review the available scientific evidence assessing the potential ergogenic value of L-citrulline supplementation on vascular function and exercise performance in humans. In addition, research that has investigated the potential synergistic effects of L-citrulline with other dietary ingredients (e.g., arginine, antioxidants, nitrates, and branched-chain amino acids) is reviewed. Oral L-citrulline and citrulline malate supplementation have shown to increase plasma citrulline and arginine concentrations, along with total nitrate and nitrite concentrations. Although blood flow enhancement is a proposed mechanism for the ergogenic potential of L-citrulline, evidence supporting acute improvements in vasodilation and skeletal muscle tissue perfusion after supplementation is scarce and inconsistent. Nevertheless, several studies have reported that L-citrulline supplementation can enhance exercise performance and recovery. Given the positive effects observed from some investigations, future studies should continue to investigate the effects of both acute and chronic supplementation with L-citrulline and citrulline malate on markers of blood flow and exercise performance and should seek to elucidate the mechanism underlying such effects.
Topics: Amino Acids, Branched-Chain; Antioxidants; Arginine; Biomarkers; Citrulline; Dietary Supplements; Drug Therapy, Combination; Exercise; Humans; Malates; Muscle, Skeletal; Nitrates
PubMed: 31977835
DOI: 10.1519/JSC.0000000000003426 -
Advanced Healthcare Materials Jan 2020Volumetric muscle loss (VML) is a devastating loss of muscle tissue that overwhelms the native regenerative properties of skeletal muscle and results in lifelong... (Review)
Review
Volumetric muscle loss (VML) is a devastating loss of muscle tissue that overwhelms the native regenerative properties of skeletal muscle and results in lifelong functional deficits. There are currently no treatments for VML that fully recover the lost muscle tissue and function. Tissue engineering presents a promising solution for VML treatment and significant research has been performed using tissue engineered muscle constructs in preclinical models of VML with a broad range of defect locations and sizes, tissue engineered construct characteristics, and outcome measures. Due to the complex vascular and neural anatomy within skeletal muscle, regeneration of functional vasculature and nerves is vital for muscle recovery following VML injuries. This review aims to summarize the current state of the field of skeletal muscle tissue engineering using 3D constructs for VML treatment with a focus on studies that have promoted vascular and neural regeneration within the muscle tissue post-VML.
Topics: Animals; Blood Vessels; Humans; Hydrogels; Muscle, Skeletal; Muscular Diseases; Regeneration; Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 31622051
DOI: 10.1002/adhm.201900626 -
Methods in Molecular Biology (Clifton,... 2016Volumetric muscle loss (VML) injury is prevalent in severe extremity trauma and is an emerging focus area among orthopedic and regenerative medicine fields. VML injuries...
Volumetric muscle loss (VML) injury is prevalent in severe extremity trauma and is an emerging focus area among orthopedic and regenerative medicine fields. VML injuries are the result of an abrupt, frank loss of tissue and therefore of different etiology from other standard rodent injury models to include eccentric contraction, ischemia reperfusion, crush, and freeze injury. The current focus of many VML-related research efforts is to regenerate the lost muscle tissue and thereby improve muscle strength. Herein, we describe a VML model in the anterior compartment of the hindlimb that is permissible to repeated neuromuscular strength assessments and is validated in mouse, rat, and pig.
Topics: Animals; Mice; Models, Animal; Muscle Contraction; Muscle Strength; Muscle, Skeletal; Organ Size; Rats; Swine; Wounds and Injuries
PubMed: 27492162
DOI: 10.1007/978-1-4939-3810-0_2 -
Biomaterials Mar 2020Skeletal muscle tissue can be created in vitro by tissue engineering approaches, based on differentiation of muscle stem cells. Several approaches exist and generally... (Review)
Review
Skeletal muscle tissue can be created in vitro by tissue engineering approaches, based on differentiation of muscle stem cells. Several approaches exist and generally result in three dimensional constructs composed of multinucleated myofibers to which we refer as myooids. Engineering methods date back to 3 decades ago and meanwhile a wide range of cell types and scaffold types have been evaluated. Nevertheless, in most approaches, myooids remain very small to allow for diffusion-mediated nutrient supply and waste product removal, typically less than 1 mm thick. One of the shortcomings of current in vitro skeletal muscle organoid development is the lack of a functional vascular structure, thus limiting the size of myooids. This is a challenge which is nowadays applicable to almost all organoid systems. Several approaches to obtain a vascular structure within myooids have been proposed. The purpose of this review is to give a concise overview of these approaches.
Topics: Muscle, Skeletal; Tissue Engineering; Tissue Scaffolds
PubMed: 31999964
DOI: 10.1016/j.biomaterials.2019.119708 -
Advanced Materials (Deerfield Beach,... Mar 2022Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current... (Review)
Review
Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current treatments result in variable functional recovery, while reconstructive surgery, as the gold-standard approach, is limited due to donor shortage, donor-site morbidity, and limited functional recovery. Skeletal muscle tissue engineering (SMTE) has generated enthusiasm as an alternative solution for treatment of injured tissue and serves as a functional disease model. Recently, bioprinting has emerged as a promising tool for recapitulating the complex and highly organized architecture of skeletal muscles at clinically relevant sizes. Here, skeletal muscle physiology, muscle regeneration following injury, and current treatments following muscle loss are discussed, and then bioprinting strategies implemented for SMTE are critically reviewed. Subsequently, recent advancements that have led to improvement of bioprinting strategies to construct large muscle structures, boost myogenesis in vitro and in vivo, and enhance tissue integration are discussed. Bioinks for muscle bioprinting, as an essential part of any bioprinting strategy, are discussed, and their benefits, limitations, and areas to be improved are highlighted. Finally, the directions the field should expand to make bioprinting strategies more translational and overcome the clinical unmet needs are discussed.
Topics: Bioprinting; Muscle, Skeletal; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds
PubMed: 34773667
DOI: 10.1002/adma.202105883 -
Cells Aug 2019Circular RNA (circRNA) is a novel class of non-coding RNA generated by pre-mRNA back splicing, which is characterized by a closed-loop structure. Although circRNAs were... (Review)
Review
Circular RNA (circRNA) is a novel class of non-coding RNA generated by pre-mRNA back splicing, which is characterized by a closed-loop structure. Although circRNAs were firstly reported decades ago, their regulatory roles have not been discovered until recently. In this review, we discussed the putative biogenesis pathways and regulatory functions of circRNAs. Recent studies showed that circRNAs are abundant in skeletal muscle tissue, and their expression levels are regulated during muscle development and aging. We, thus, characterized the expression profile of circRNAs in skeletal muscle and discussed regulatory functions and mechanism-of-action of specific circRNAs in myogenesis. The future investigation into the roles of circRNAs in both physiological and pathological conditions may provide novel insights in skeletal muscle development and provide new therapeutic strategies for muscular diseases.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Muscle Development; Muscle, Skeletal; RNA, Circular
PubMed: 31412632
DOI: 10.3390/cells8080885 -
Advanced Materials (Deerfield Beach,... Dec 2016Repair of damaged skeletal-muscle tissue is limited by the regenerative capacity of the native tissue. Current clinical approaches are not optimal for the treatment of... (Review)
Review
Repair of damaged skeletal-muscle tissue is limited by the regenerative capacity of the native tissue. Current clinical approaches are not optimal for the treatment of large volumetric skeletal-muscle loss. As an alternative, tissue engineering represents a promising approach for the functional restoration of damaged muscle tissue. A typical tissue-engineering process involves the design and fabrication of a scaffold that closely mimics the native skeletal-muscle extracellular matrix (ECM), allowing organization of cells into a physiologically relevant 3D architecture. In particular, anisotropic materials that mimic the morphology of the native skeletal-muscle ECM, can be fabricated using various biocompatible materials to guide cell alignment, elongation, proliferation, and differentiation into myotubes. Here, an overview of fundamental concepts associated with muscle-tissue engineering and the current status of muscle-tissue-engineering approaches is provided. Recent advances in the development of anisotropic scaffolds with micro- or nanoscale features are reviewed, and how scaffold topographical, mechanical, and biochemical cues correlate to observed cellular function and phenotype development is examined. Finally, some recent developments in both the design and utility of anisotropic materials in skeletal-muscle-tissue engineering are highlighted, along with their potential impact on future research and clinical applications.
Topics: Animals; Biocompatible Materials; Cell Differentiation; Extracellular Matrix; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Tissue Engineering; Tissue Scaffolds
PubMed: 27865007
DOI: 10.1002/adma.201600240