Electrical stimulation increases hypertrophy and metabolic flux in tissue-engineered human skeletal muscle

Khodabukus, Alastair; Madden, Lauran; Prabhu, Neel K.; Koves, Timothy R.; Jackman, Christopher P.; Muoio, Deborah M.

doi:10.1016/j.biomaterials.2018.08.058

Cited by 141 publications

(158 citation statements)

References 115 publications

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“…Higher levels of resistance are likely to provide more load to the muscles, leading to more effective myophysiological changes, but this can lead to rapid muscle fatigue and even temporary pain. Resistance training increases the number of myofibres, which causes muscle hypertrophy, and a concomitant increase in strength . Previous studies have shown resistance training in swallow‐related muscles, including tongue muscle, have resulted in increased muscle strength and thickness, similar to the results of this study.…”

Section: Discussionsupporting

confidence: 88%

Effect of tongue‐strengthening training combined with a tablet personal computer game in healthy adults

Hwang

Kim

Lee

et al. 2020

J of Oral Rehabilitation

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Background: Game-based training has been shown to improve behavioural motor learning in various medical fields including rehabilitation.Objectives: This study aimed to investigate the effects of a tablet PC (personal computer) game-based tongue training on tongue strength, thickness and compliance in healthy adults.Methods: This study recruited 30 healthy volunteers. Subjects were randomly assigned to two groups (n = 15/group). Group 1 performed game-based tongue training, and group 2 performed tongue resistance training using the Iowa Oral Performance Instrument. Both groups performed the same tongue exercises as follows: frequency (isotonic = 30 times × 3, isometric = 20 seconds × 3), intensity (70% of 1-repeated maximum contraction) and intervention period (5 days for 6 weeks). The primary outcomes were tongue muscle strength and thickness. Secondary outcomes were assessed using a 0-to-10 numerical rating self-report scale that included motivation, interest/fun, physical effort and muscle fatigue/pain. Results:Both groups showed significant improvement in tongue strength and thickness, but there were no significant differences between the groups after the intervention. The self-report scale numerical rating revealed that group 1 had significantly higher motivation and interest/fun after the exercise than group 2. Group 1 had expended a significantly lower physical effort than group 2. No significant differences were noted between the 2 groups for muscle fatigue/pain. Conclusion:This study showed that both exercises had similar effects on tongue strength and thickness increase in healthy adults, but game-based tongue training was more fun and physically less demanding. K E Y W O R D Sgame, strength, thickness, tongue, training

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Section: Discussionsupporting

confidence: 88%

Effect of tongue‐strengthening training combined with a tablet personal computer game in healthy adults

Hwang

Kim

Lee

et al. 2020

J of Oral Rehabilitation

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“…Resistance training that provides effective loads increases the thickness of skeletal muscles. This effect is associated with an increase in the number of myofibers and consequently an increase in thickness, which is called muscle hypertrophy . Previous studies investigating healthy adults have reported physiological changes in muscles, including in the muscle thickness and cross‐sectional area, caused by resistance training of the limbs .…”

Section: Discussionmentioning

confidence: 99%

Effects of lingual strength training on oropharyngeal muscles in South Korean adults

Park

Hwang

Kim

et al. 2019

J of Oral Rehabilitation

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The lingual muscle is a component of the stomatognathic system that comprises fixed (mandible, maxilla, dental arches, temporomandibular joints and the hyoid bone) and dynamic structures (masticatory, supra-and infrahyoid muscles and the oro-facial muscle such as lingual, lips and cheek muscles) that act synergistically to perform stomatognathic functions including mastication, swallowing and speech. [1][2][3] Neurological disorders such as stroke cause weakening of the skeletal muscles. The lingual muscle also contains skeletal muscles and is therefore affected by factors causing skeletal Abstract Background: Lingual strength training (LST) has been reported to positively affect the activation of submental muscles, as well as to increase lingual muscle strength.However, there is little evidence to support its effectiveness.Objectives: This study aimed to investigate the effect of LST on the strength and thickness of oropharyngeal muscles in healthy adults. Methods:The study included 30 subjects who were assigned to the experimental (n = 15) and the control groups (n = 15). The experimental group performed LST based on tongue-to-palate resistance exercise method. LST was categorised as isometric and isotonic exercise. The intervention was performed five times a week for 6 weeks. The control group did not receive any intervention. The lingual strength was measured using the Iowa Oral Performance Instrument. Changes in the thickness of the mylohyoid and the digastric muscles and the lingual were assessed ultrasonographically.Results: After the intervention, the thickness of the mylohyoid and the digastric muscles in the experimental group was significantly greater than that in the control group (P = 0.037 and 0.042). Conclusion:This study demonstrated that LST increases the thickness and the strength of oropharyngeal muscles. Therefore, LST is a useful option in patients with dysphagia or in elderly patients prone to swallowing dysfunction. K E Y W O R D S exercise, lingual, swallowing, ultrasonography | 1037 PARK et Al.

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“…Whereas decreased half relaxation time has been outlined to be indicative of calcium re-uptake in the SR via the SERCA pump, with increased SERCA1 mRNA transcription evident following electrical stimulation of 3D muscle tissue. 45 Both functional measures were significantly decreased in time following innervation, indicating an enhanced efficiency of the molecular mechanisms of muscle contraction. Importantly, neuromuscular tissues using primary rat cells reported increases in time to peak force and half relaxation time measures upon innervation, suggesting that alterations in the excitability of bioengineered motor units appears sensitive across species.…”

Section: Discussionmentioning

confidence: 96%

Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions

Rimington

Fleming

Capel

et al. 2020

Preprint

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Investigations of the human neuromuscular junction (NMJ) have predominately utilised 11 experimental animals and model organisms. Consequently, there remains a paucity of data regarding the 12 development of the human NMJ and a lack of systems that enable temporal investigation of the motor unit. 13This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor 14 unit. Separate maturation of primary human skeletal muscle and iPSC derived motor neurons seeks to 15 accurately represent neuromuscular development via controlled addition of motor axons following primary 16 myogenesis. Spheroid cultures of motor neuron progenitors augmented the transcription of OLIG2, ISLET1 17 and SMI32 motor neuron mRNAs ~400, ~150 and ~200-fold respectively. Axon projections of adhered motor 18 neuron spheroids exceeded 1000µm in monolayer, with transcription of SMI32 and VACHT mRNAs further 19 enhanced in a concentration dependent manner within optimised 3D type I collagen extracellular matrices. 20Bioengineered skeletal muscles produce functional forces, demonstrate increased acetylcholine receptor 21 (AChR) clustering, and transcription of MUSK and LRP4 mRNAs indicating enhanced organisation of the 22 post-synaptic membrane. Dosed integration of motor neuron spheroids outlined the motor pool required to 23 functionally innervate muscle tissues in 3D, generating physiologically functional human NMJs that evidence 24 pre-and post-synaptic membrane and motor nerve terminal co-localisation. Spontaneous firing was 25 significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition 26 of the AChR. Finally, functional analyses outlined decreased time to peak twitch and half relaxation times, 27indicating enhanced physiology of excitation contraction coupling of NMJs within innervated motor units. 28The neuromuscular junction (NMJ) is the specialised synapse between the post-synaptic skeletal muscle fibre 31 and pre-synaptic terminal of the efferent motor nerve axon. Its function is to elicit contraction of the peripheral 32 musculature and consequently control locomotion of the skeleton via a co-ordinated mechanosensory-motor 33 circuit. The NMJ comprises an organised assembly of protein complexes (Agrin-Lrp4-MuSK-Dok7) that form 34 the highly specialised synaptic basal lamina; the function of which is to stabilise the synapse and facilitate the 35 intricate biochemical processes that initiate muscular excitability and contraction. 1,2 Neuronal action potential 36 induces an influx of calcium ions at the motor nerve terminal that elicits fusion of synaptic vesicles at active 37 zones on the terminal membrane. Vesicle fusion mediates the release of the neurotransmitter acetylcholine 38 (ACh) which diffuses through the synaptic cleft and binds nicotinic acetylcholine receptors (AChR) on the 39 post-synaptic membrane. 3 This depolarisation opens voltage-gated sodium ion channels and generates the 40 action potential required for excitation contraction co...

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Electrical stimulation increases hypertrophy and metabolic flux in tissue-engineered human skeletal muscle

Cited by 141 publications

References 115 publications

Effect of tongue‐strengthening training combined with a tablet personal computer game in healthy adults

Effect of tongue‐strengthening training combined with a tablet personal computer game in healthy adults

Effects of lingual strength training on oropharyngeal muscles in South Korean adults

Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions

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