At the Society of Toxicology 58th Annual Meeting and ToxExpo from March 10th to 14th at the Baltimore Convention Center, poster presentation on Monday March 11th 10:45am – 12:15pm Poster Board P518 Convention Center Exhibition Hall sponsored by Professor Ruth Roberts. 

TRP Channel Responses in Human iPSC-Derived Sensory Neurons Using MEA System.

Authors:  A. Odawara, Y. Kobayashi, N. Matsuda, and I. Suzuki. Tohoku Institute of Technology, Sendai, Miyagi, Japan. Sponsor: R. Roberts

Abstract:

Functional evaluation assays using human induced pluripotent stem cell (hiPSC)-derived sensory neurons are expected to predict the pain-related toxicity of drugs and the pharmacological effects. However, evaluation assays in hiPSC-derived sensory neurons has not been established, and transient receptor potential (TRP) channel responses to pain-related molecules are also not known. In this study, we aimed to evaluate the TRP channel responses aginst pain-related molecules including anticancer drugs in cultured hiPSC-derived sensory neurons using high-throughput multi-electrode array (MEA) system. Human iPSC-derived sensory neurons were cultured on MEA chips (Presto), and the electrophysiological responses against capsaicin, menthol, allyl isothiocyanate (AITC), anticancer drug vincristine and oxaliplatin were measured by the MEA system. We firstly confirmed the expression of typical sensory marker Nav1.7, TRPV1, TRPM8, and TRPA1 using immunostaining in culture hiPSC-derived sensory neurons at 8 weeks culture. Evoked responses against capsaicin, menthol, and AITC administration were detected using MEA system. To confirm the responses depending on each TRP channel, we examined the responses in presence of each channel antagonist. As the responses almost disappeared in presence of each channel blocker, these responses were confirmed to be TRP channel specific responses. The evoked responses against anticancer drug vincristine and oxaliplatin administration were also detected. Next, we examined whether the increase of cold sensitivities occur in presence of anticancer drug oxaliplatin in vitro hiPSC-derived sensory neurons. The responses against AITC were increased in presence oxaliplatin and in a concentration-dependent manner. In summary, we have succeeded in detecting the electrophysiological pain reponses against capsaicin, menthol, allyl isothiocyanate (AITC), anticancer drug vincristine and oxaliplatin in hiPSC-derived sensory neurons using MEA system. We found that the increase of cold sensitivities in vivo phenomenon was also detected in vitro hiPSC-derived sensory neurons. MEA measurements using hiPSC-derived sensory neurons are useful to pain evaluation assay in human peripheral nervous system.

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