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Higher Sensitivity of Myotoxicity Detection

Yoran Margaron, Mathieu Fernandes, Delphine Morales, Pauline Poydenot, Alexandra Fuchs, Sébastien Degot CYTOO, Grenoble, France

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Introduction

Withdrawal of statins from the market lead to a considerable economic burden for the pharmaceutical industry, and unraveled the need to access more physiologically relevant in vitro models dedicated to muscle damage detection. In this context, we have developed a more mature myotube model improving the sensitivity of myotoxic drug detection. When cultured on CYTOO micropatterns, primary human myoblasts differentiated faster into myotubes and presented a higher degree of maturation compared to standard culture conditions, i.e. a higher level of striation. Moreover, myotube morphology was standardized which enabled accessing new parameters for their characterization upon drug treatment. To further demonstrate the benefits of our model, we developed dedicated image analysis algorithms and screened reference myotoxic compounds to assess a potential gain of sensitivity compared to standard culture methods.

RESULTS: We demonstrated that this model was robust and compatible with High Content Screening with increased Z’ factors compared to standard assays. In addition, the combination of highly mature myotubes and enhanced image analysis capacities enabled highly sensitive detection of myotoxic drugs over standard assays.

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