Development of a functional sarcopenia model utilizing a microcantilever microphysiological system as a phenotypic...

Area of Science:

• Biomedical Engineering
• Cell Biology
• Muscle Physiology

Background:

• Sarcopenia is characterized by skeletal muscle mass and function decline, often co-occurring with inflammatory diseases.
• Understanding sarcopenia's mechanisms requires advanced in vitro models that mimic disease progression.

Purpose of the Study:

• To develop and validate a novel in vitro functional model for studying sarcopenia.
• To assess the long-term effects of TNF-alpha induced inflammation on skeletal muscle cells.

Main Methods:

• Human induced pluripotent stem cell-derived skeletal muscle cells were cultured and treated with TNF-alpha.
• Muscle function was assessed using microcantilever measurements of contraction amplitude, force, and fatigue.
• Myotube width and reactive oxygen species production were monitored over 32 days.

Main Results:

• The model demonstrated sustained reduction in myotube width and impaired muscle function for up to 32 days post-treatment.
• Increased reactive oxygen species production indicated disease progression and tissue degradation.
• The model successfully recapitulated key physiological signatures of sarcopenia.

Conclusions:

• This study presents the first microphysiological system for sarcopenia evaluation on a microcantilever platform.
• This model can be utilized for therapeutic screening and integrated into multi-organ systems to study inflammatory comorbidities.