Developing an in vitro myobundle model system for pathophysiological studies of human skeletal muscle
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Date
2015-09-17
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Abstract
Existing in vitro models for liver, lung, and cardiac tissue have made recent notable progress, however a predictive model of human skeletal muscle does not exist. While, two-dimensional cultures of myoblasts are well known, these cultures lack the organization and function of a native muscle. Therefore, the usefulness of these existing models in pharmacological studies and disease modeling is limited. The purpose of this study is to adapt a novel three-dimensional skeletal muscle model and confirm that it is usable in future studies. This will be done by creating custom silicone molds and teflon frames in which various myoblast cell lines and myocytes derived from human PSCs will be cultured. Thus far, attachment to the frame has been observed but cell death has soon followed. Our solution is to proceed to vary the cell type and concentration in order to find cells for optimal growth in the three-dimensional matrix. Our observations do prove, however, that formation of the myobundle is possible with this model and that with continued alteration the myobundle should survive for use in further testing. Ultimately, these fabricated three-dimensional myobundles should be electrically and chemically responsive and are reported to contract spontaneously. Use of human iPSCs cells will allow for production of human muscle cells and will also allow generation of patient specific cells that can harbor mutations leading to disease states, such as muscular dystrophy. A physiologically correct in vitro skeletal muscle model can provide a tool for pharmacological testing and an alternative to animal studies, mitigating ethical considerations and reducing the number of in vivo and ex vivo models.
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Biological and Biomedical Sciences
Keywords
muscle, myobundle, physiology, model, in vitro, cell biology