Engineered skeletal muscle tissues can be used for in vitro studies that require physiologically relevant models of native tissues. Herein, we describe the development of a three-dimensional (3D) ...skeletal muscle tissue that recapitulates the architectural and structural complexities of muscle within a microfluidic device. Using a 3D photo-patterning approach, we spatially confined a cell-laden gelatin network around two bio-inert hydrogel pillars, which induce uniaxial alignment of the cells and serve as anchoring sites for the encapsulated cells and muscle tissues as they form and mature. We have characterized the tissue morphology and strain profile during differentiation of the cells and skeletal muscle tissue formation by using a combination of fluorescence microscopy and computational tools. The time-dependent strain profile suggests the existence of individual cells within the gelatin matrix, which differentiated to form a multinucleated skeletal muscle tissue bundle as a function of culture time. We have also developed a method to calculate the passive tension generated by the engineered muscle tissue bundles suspended between two pillars. Finally, as a proof-of-concept we have examined the applicability of the skeletal muscle-on-chip system as a screening platform and in vitro muscle injury model. We studied the dose-dependent effect of cardiotoxin on the engineered muscle tissue architecture and its subsequent effect on the passive tension. This simple yet effective tool can be appealing for studies that necessitate the analysis of skeletal muscle structure and function, including preclinical drug discovery and development.
The purpose of this study was to evaluate muscular adaptations between low-, moderate-, and high-volume resistance training protocols in resistance-trained men.
Thirty-four healthy resistance-trained ...men were randomly assigned to one of three experimental groups: a low-volume group performing one set per exercise per training session (n = 11), a moderate-volume group performing three sets per exercise per training session (n = 12), or a high-volume group performing five sets per exercise per training session (n = 11). Training for all routines consisted of three weekly sessions performed on nonconsecutive days for 8 wk. Muscular strength was evaluated with one repetition maximum (RM) testing for the squat and bench press. Upper-body muscle endurance was evaluated using 50% of subjects bench press 1RM performed to momentary failure. Muscle hypertrophy was evaluated using B-mode ultrasonography for the elbow flexors, elbow extensors, mid-thigh, and lateral thigh.
Results showed significant preintervention to postintervention increases in strength and endurance in all groups, with no significant between-group differences. Alternatively, while all groups increased muscle size in most of the measured sites from preintervention to postintervention, significant increases favoring the higher-volume conditions were seen for the elbow flexors, mid-thigh, and lateral thigh.
Marked increases in strength and endurance can be attained by resistance-trained individuals with just three 13-min weekly sessions over an 8-wk period, and these gains are similar to that achieved with a substantially greater time commitment. Alternatively, muscle hypertrophy follows a dose-response relationship, with increasingly greater gains achieved with higher training volumes.
We provide an update on the recent advances in nutrition research regarding the role of protein intake in the development and treatment of sarcopenia of aging.
Specific muscle mass, strength and ...function cut-points for the diagnosis of sarcopenia have been identified. There is mounting evidence, as highlighted by multiple consensus statements, that the Recommended Dietary Allowance (0.8 g/kg body weight) may be inadequate to promote optimal health in older adults. Recent research indicates that in addition to total daily protein intake the timing of protein intake is also important to best stimulate muscle protein synthesis, and maintain muscle mass and function in older adults.
Recent evidence suggests that the Recommended Dietary Allowance for protein is inadequate, and that the timing and distribution of protein consumption throughout daily meals may be as important as the total quantity. Research has continued to advance our understanding of protein's effects on muscle metabolism; however, there remains a need for large, long-term, randomized clinical trials examining whether the positive effects of dietary protein on muscle metabolism seen in acute studies will translate over the long term into gains of muscle mass, function, and the overall health of older adults.
Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Here, in homeostatic skeletal muscle, we identify two quiescent ...stem-cell states distinguished by relative CD34 expression: CD34
, with stemness properties (genuine state), and CD34
, committed to myogenic differentiation (primed state). The genuine-quiescent state is unexpectedly preserved into later life, succumbing only in extreme old age due to the acquisition of primed-state traits. Niche-derived IGF1-dependent Akt activation debilitates the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive a primed-to-genuine state conversion, whereas FoxO inactivation deteriorates the genuine state at a young age, causing regenerative failure of muscle, as occurs in geriatric mice. These findings reveal transcriptional determinants of stem-cell heterogeneity that resist ageing more than previously anticipated and are only lost in extreme old age, with implications for the repair of geriatric muscle.
Older adults undergoing age-related decrements in muscle health can benefit substantially from resistance exercise training, a potent stimulus for whole muscle and myofiber hypertrophy, neuromuscular ...performance gains, and improved functional mobility. With the use of advancing technologies, research continues to elucidate the mechanisms of and heterogeneity in adaptations to resistance exercise training beyond differences in exercise prescription. This review highlights the current knowledge in these areas and emphasizes knowledge gaps that require future attention of the field.
This study aimed (i) to determine the reliability of two-dimensional ultrasonography for the assessment of biceps femoris long head (BFlh) architectural characteristics and (ii) to determine whether ...limbs with a history of strain injury in the BFlh display different architecture and eccentric strength compared to uninjured limbs.
This case-control study (control n = 20, injured group n = 16, males) assessed the BFlh architecture at rest and during graded isometric contractions using two-dimensional ultrasonography. The control group were assessed three times (>24 h apart) to determine reliability. Previously injured individuals were evaluated once.
The assessment of BFlh architecture was highly reliable (intraclass correlations >0.90). Fascicle length (P < 0.001; d range = 0.67-1.34) and fascicle length relative to muscle thickness (P < 0.001; d range = 0.58-0.85) of the previously injured BFlh were significantly less than the contralateral uninjured BFlh at all intensities. Pennation angle of the previously injured BFlh was significantly greater (P < 0.001; d range = 0.62-0.88) than the contralateral uninjured BFlh at all intensities. Eccentric strength in the previously injured limb was significantly lower than that in the contralateral limb (-15.4%; -52.5 N, 95% confidence interval = -76.2 to -28.4; P < 0.001, d = 0.56).
These data indicate that two-dimensional ultrasonography is reliable for assessing BFlh architecture at rest and during graded isometric contractions. Fascicle length, fascicle length relative to muscle thickness, and pennation angle are significantly different in previously injured BFlh compared to an uninjured contralateral BFlh. Eccentric strength of the previously injured limb is also significantly lower than that of the uninjured contralateral limb. These findings have implications for rehabilitation and injury prevention practices, which should consider altered architectural characteristics.
Skeletal muscle is the largest tissue in the body and loss of its function or its regenerative properties results in debilitating musculoskeletal disorders. Understanding the mechanisms that drive ...skeletal muscle formation will not only help to unravel the molecular basis of skeletal muscle diseases, but also provide a roadmap for recapitulating skeletal myogenesis
from pluripotent stem cells (PSCs). PSCs have become an important tool for probing developmental questions, while differentiated cell types allow the development of novel therapeutic strategies. In this Review, we provide a comprehensive overview of skeletal myogenesis from the earliest premyogenic progenitor stage to terminally differentiated myofibers, and discuss how this knowledge has been applied to differentiate PSCs into muscle fibers and their progenitors
.
Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in ...individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.
Dystrophin is a long rod-shaped protein that connects the subsarcolemmal cytoskeleton to a complex of proteins in the surface membrane (dystrophin protein complex, DPC), with further connections via ...laminin to other extracellular matrix proteins. Initially considered a structural complex that protected the sarcolemma from mechanical damage, the DPC is now known to serve as a scaffold for numerous signaling proteins. Absence or reduced expression of dystrophin or many of the DPC components cause the muscular dystrophies, a group of inherited diseases in which repeated bouts of muscle damage lead to atrophy and fibrosis, and eventually muscle degeneration. The normal function of dystrophin is poorly defined. In its absence a complex series of changes occur with multiple muscle proteins showing reduced or increased expression or being modified in various ways. In this review, we will consider the various proteins whose expression and function is changed in muscular dystrophies, focusing on Ca(2+)-permeable channels, nitric oxide synthase, NADPH oxidase, and caveolins. Excessive Ca(2+) entry, increased membrane permeability, disordered caveolar function, and increased levels of reactive oxygen species are early changes in the disease, and the hypotheses for these phenomena will be critically considered. The aim of the review is to define the early damage pathways in muscular dystrophy which might be appropriate targets for therapy designed to minimize the muscle degeneration and slow the progression of the disease.
Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural ...and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.
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