Poster
85

Development of in vivo-like cell-based screening system for rapid and quantitative toxicity and efficacy predictions against epidermis activation

Discussion

Animal test is widely used for compound toxicity and evaluation although the results obtained are different from human clinical test even using a monkey.
For in vitro compound screening against epidermis activation, cocultivation of keratinocyte with a target compound is often hired since animal test is inhibited for cosmetic development in EU. The 3D cell culture is performed using extracellular matrix and additionally fibroblast cells from dermis to reconstitute skin structure. However, this requires long time culture duration (ca. 1 month) because the method is based on endpoint. Furthermore, it will not allow simultaneous determination of toxicity of apoptosis and necrosis, and efficacy. Moreover, the cell activity decreases during long term culture causing low experimental repeatability.
We have developed a custom-made human cell-based assay device, High-Precision Surface Plasmon Resonance (HP-SPR), and in vivo-like method for anti-cancer drug screening. This monitors early stage of mitochondrial response to stimuli within live cells giving endpoint toxicity and efficacy predictions rapidly (ca. 1 hour) without cell culture.
We proved HP-SPR validity for prediction of target compound toxicity and efficacy at physiological concentration for epidermis activation, and successfully established new in vivo-like test.

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