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The effect of serum origin on tissue engineered skeletal muscle function
Alastair Khodabukus1, Keith Baar
1Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA, 95616, USA.
Journal of Cellular Biochemistry
|August 23, 2014
Summary
Hormonal differences in fetal bovine serum (FBS) significantly alter engineered skeletal muscle function. US-origin serum promotes a slower muscle phenotype by affecting calcium handling proteins, not myosin expression.
Area of Science:
- Muscle physiology
- Cellular biology
- Biochemistry
Background:
- Skeletal muscle phenotype is influenced by genetics, hormones, and electrical activity.
- In vivo studies make it challenging to isolate the impact of individual factors on muscle contraction dynamics.
- Previous experiments using C2C12 cells showed differing muscle contraction dynamics between EU and US-sourced serum.
Purpose of the Study:
- To investigate if the hormonal environment, specifically the source of fetal bovine serum (FBS), influences engineered skeletal muscle phenotype.
- To determine the molecular mechanisms underlying observed differences in muscle contraction dynamics.
Main Methods:
- Engineered skeletal muscles using the same C2C12 cell clone in both EU and US-origin FBS.
- Assessed muscle contraction dynamics, including time-to-peak tension, half relaxation time, and fatigue resistance.
- Analyzed protein expression related to calcium handling (DHPR, CSQ, TnT, SERCA, parvalbumin) and myosin heavy chain.
Main Results:
- Muscles engineered with US-origin FBS exhibited a slower phenotype, with increased time-to-peak tension and half relaxation, and improved fatigue resistance.
- Myosin heavy chain expression remained unchanged despite altered contraction speed.
- Significant shifts in calcium handling proteins were observed: lower DHPR, higher slow CSQ and slow TnT, higher slow SERCA, and lower parvalbumin.
- Metabolic enzymes showed partial shifts, but traditional regulators of muscle phenotype did not explain the observed functional changes.
Conclusions:
- Hormonal variations in FBS from different geographical origins (US vs. EU) can profoundly alter engineered skeletal muscle function.
- The shift towards a slower muscle phenotype is mediated by changes in calcium handling proteins and dynamics, rather than myosin heavy chain expression.
- This study highlights the critical role of the hormonal milieu in dictating skeletal muscle characteristics and provides insights into calcium regulation mechanisms.

