Characteristics of the Protocols Used in Electrical Pulse Stimulation of Cultured Cells for Mimicking In Vivo Exercise: A Systematic Review, Meta-Analysis, and Meta-Regression

Abstract

While exercise benefits a wide spectrum of diseases and affects most tissues and organs, many aspects of its underlying mechanistic effects remain unsolved. In vitro exercise, mimicking neuronal signals leading to muscle contraction in vitro, can be a valuable tool to address this issue. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for this systematic review and meta-analysis, we searched EMBASE and PubMed (from database inception to 4 February 2022) for relevant studies assessing in vitro exercise using electrical pulse stimulation to mimic exercise. Meta-analyses of mean differences and meta-regression analyses were conducted. Of 985 reports identified, 41 were eligible for analysis. We observed variability among existing protocols of in vitro exercise and heterogeneity among protocols of the same type of exercise. Our analyses showed that AMPK, Akt, IL-6, and PGC1a levels and glucose uptake increased in stimulated compared to non-stimulated cells, following the patterns of in vivo exercise, and that these effects correlated with the duration of stimulation. We conclude that in vitro exercise follows motifs of exercise in humans, allowing biological parameters, such as the aforementioned, to be valuable tools in defining the types of in vitro exercise. It might be useful in transferring obtained knowledge to human research.

Investigating the Combined Effects of Mechanical Stress and Nutrition on Muscle Hypertrophic Signals Using Contractile 3D-Engineered Muscle (3D-EM)

“…We think this discrepancy may be due to the long intervention time of EPS. Previous research showed that the increase in duration will lead to a significant downward trend in the effect of EPS [ 65 ]. Basically, mechanical stress is an important factor causing muscle hypertrophy in in vitro models, so, it is necessary to explore the conditions that promote muscle hypertrophy solely under EPS in the 3D-EM to mimic hypertrophic effects seen in the 2D muscle cells, such as duration and frequency of EPS, which might be important factors to mediate specific cellular signaling [ 24 ].…”

Influence of Amino Acids and Exercise on Muscle Protein Turnover, Particularly in Cancer Cachexia

“…This low-frequency EPS technique has been proven to increase glucose uptake, mitochondrial content, cellular oxidation, citrate synthase activity, insulin sensitivity, activation of AMPK, IL-6, and anti-inflammatory activity [146,151,152]. Different EPS protocols exist today, and new ones are continuously being developed to mimic various forms of exercise training, and each has its pros and cons [153]. Although EPS cannot replicate all the conditions of in vivo exercises, as it lacks motor neurons, neuromuscular junctions, blood flow, and innervation, it still has great potential in the study of muscle contraction in myotubes in vitro.…”

Translating In Vitro Models of Exercise in Human Muscle Cells: A Mitocentric View

“…Studies that used EPS as an in vitro model of exercise mimicking acute versus chronic or aerobic versus resistance training have mostly been described in the immortalized rodent cell lines C2C12 and L6 (24,25). From our review of the literature, 10 studies defined their EPS protocol as that of an "exercise-like" treatment on HSkMCs (26)(27)(28)(29)(30)(31)(32)(33), investigating exercise-mediated signaling mechanisms (26,(28)(29)(30)32,33), expression of mitochondrial-related genes (21,27,31), substrate metabolism (27,28,30,33,56), and measurements of mitochondrial quantity (27,28,(30)(31)(32)(33)) (Table ).…”

“…A direct comparison of an in vitro EPS protocol to a specific in vivo mode of exercise has been complicated to recreate. There is no current consensus as to what EPS parameters should be used, (i.e., voltage, time, duration, and frequency of pulses), to mimic any type of exercise training (24). Whether EPS protocols mimic either aerobic or resistance exercise training is still under debate because of the usage of supraphysiological stimulation levels.…”