In the development process for drugs used to treat skeletal muscle, cell‐based contractile force assays have been considered as a useful in vitro test. Immortalized human myogenic cells are promising as cell sources for reproducible and well‐characterized in vitro models. In this study, it is investigated whether immortalized human myogenic cells, Hu5/KD3, have suitable contractile ability and the potential to be used as cell sources for contractile force assays. Muscle tissues are fabricated using Hu5/KD3 cells on the microfabricated devices used to measure contractile force. The tissues generate a tetanic force of ≈30 µN in response to the electrical pulse stimulation (EPS). Gene expression analysis of the myosin heavy chain (MYH) isoform indicates that the tissues mostly consisted of muscle fibers expressing MYH7 or/and MYH8. The addition of dexamethasone or lovastatin decreases the contractile force of the tissues, indicating that the tissues have the potential to evaluate drug candidates designed to treat muscle atrophy or statin‐induced myopathy. It is also demonstrated that the contractile force of tissues increased when EPS is applied as an artificial exercise. These results indicate that the Hu5/KD3 tissues can be employed for contractile force assays and would be useful for in vitro human skeletal muscle models.
Skeletal muscle atrophy is characterized by decreases in protein content, myofiber diameter, and contractile force generation. As muscle atrophy worsens the quality of life, the development of anti‐atrophic substances is desirable. In this study, we aimed to demonstrate a screening process for anti‐atrophic peptides using photo‐cleavable peptide array technology and human contractile atrophic muscle models. We developed a 96‐well system and established a screening process with less variability. Dexamethasone‐induced human atrophic tissue was constructed in the system. Eight peptides were selected from the literature and used for the screening of peptides for preventing the decrease of the contractile forces of tissues. The peptide QIGFIW, which showed preventive activity, was selected as the seed sequence. As a result of amino acid substitution, we obtained QIGFIQ as a peptide with higher anti‐atrophic activity. These results indicate that the combinatorial use of the photo‐cleavable peptide array technology and 96‐well screening system could comprise a powerful approach to obtaining anti‐atrophic peptides, and suggest that the 96‐well screening system and atrophic model represent a practical and powerful tool for the development of drugs/functional food ingredients.
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