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Assessing Functional Metrics of Skeletal Muscle Health in Human Skeletal Muscle Microtissues
Published on: February 18, 2021
Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs
Adam P Sharples1, Darren J Player, Neil R W Martin
1Muscle Cellular and Molecular Physiology Research Group (MCMPRG), Institute for Sport and Physical Activity Research (ISPAR Bedford), University of Bedfordshire, Bedford, UK. a.p.sharples@googlemail.com
Aging Cell
|August 14, 2012
Summary
This study developed a 3D bioengineered skeletal muscle model using aged cells to mimic sarcopenia. This in vitro model shows reduced function and characteristics of age-related muscle degeneration, offering a platform for testing therapies.
Area of Science:
- Biomedical Engineering
- Skeletal Muscle Physiology
- Aging Research
Background:
- Sarcopenia, or skeletal muscle degeneration with age, significantly impacts elderly individuals' health and mortality.
- Current interventions for sarcopenia are challenging due to the frail condition of the target population.
- In vitro models are needed to accurately study the aged skeletal muscle niche and test therapies.
Purpose of the Study:
- To develop and characterize a 3D bioengineered skeletal muscle construct using aged cells.
- To assess if this in vitro model replicates key features of in vivo age-related muscle degeneration.
- To establish a platform for testing potential therapeutic interventions against muscle wasting.
Main Methods:
- Utilized multiple population-doubled (MPD) murine myoblasts, known for aged phenotypes, in 3D collagen matrices under uniaxial tension.
- Compared MPD constructs with parental control (CON) constructs.
- Assessed myotube size, diameter, peak force development, and gene expression related to matrix remodeling and growth factors.
Main Results:
- MPD constructs exhibited reduced myotube size and diameter compared to CON constructs.
- Peak force development was reduced in MPD constructs.
- MPD constructs showed decreased expression of MMP2, MMP9, IGF-I, IGF-IR, IGF-IEa, and MGF, with increased IGFBP2 and myostatin, indicating impaired differentiation and regeneration.
Conclusions:
- 3D bioengineered skeletal muscle constructs effectively model the in vivo cellular niche.
- MPD constructs display characteristics mirroring in vivo aged and atrophied muscle.
- This model serves as a promising in vitro test bed for developing therapies to combat age-related muscle degeneration.
