Toxics
Development of an In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neuropathy (CIPN) by Integrating a Microphysiological System (MPS) with Morphological Deep Learning of Soma and Axonal Images
Kazuki Matsuda1, Xiaobo Han1, Naoki Matsuda1, Makoto Yamanaka2 and Ikuro Suzuki1*
1Tohoku Institute of Technology (Japan)
2Ushio Inc. (Japan)
Several anticancer drugs used in cancer therapy can cause chemotherapy-induced peripheral neuropathy (CIPN), leading to reduced treatment efficacy or treatment discontinuation due to dose reduction. Therefore, there is a demand for in vitro evaluation methods to predict CIPN and understand the mechanisms of action of candidate drug compounds. In this study, we developed a method for assessing the toxicity of anticancer drugs on soma and axons using AI image analysis of microscopic observations obtained from a Nerve MPS (microphysiological system, MPS). We cultured rat dorsal root ganglion neurons in the Nerve MPS and constructed AI models (soma and axon) using images of the cell body and neurite area. Results from exposing the neurons to representative anticancer drugs known to cause CIPN showed significant soma damage with paclitaxel and oxaliplatin in the soma region, and significant axon damage with paclitaxel and vincristine in the axon region. Furthermore, these results demonstrated advantages over existing evaluation methods. Therefore, the combination of Nerve MPS and AI image analysis can provide an effective evaluation method to detect peripheral nerve toxicity and infer the mechanisms of action of candidate compounds that cause CIPN, even at low concentrations, thus enabling the prediction of the safety of new drugs.
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