Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

• DOI: 10.1016/j.scr.2017.06.006
• Publication Date: 2017-06-16T12:00:22Z
• Authors: Claudia Wing; Masaaki Komatsu; Shannon M. Delaney; Matthew Krause; Heather E. Wheeler; M. Eileen Dolan
• Keywords: Neurotoxicity; Neurite; Carboplatin; Chemotherapy-Induced Peripheral Neuropathy

The generation of induced pluripotent stem cells (iPSCs) and differentiation to composing major organs has opened up the possibility for a new model system study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons peripheral neuropathy, one most common effects chemotherapy cause dose reduction. To determine utility these in investigating neurotoxic chemotherapy, measured morphological differences neurite outgrowth, cell viability as determined by ATP levels apoptosis through measures caspase 3/7 activation following treatment clinically relevant concentrations platinating agents (cisplatin, oxaliplatin carboplatin), taxanes (paclitaxel, docetaxel nab-paclitaxel), targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), 5-fluorouracil, chemotherapeutic that does not neuropathy. We demonstrate differential sensitivity mechanistically distinct classes chemotherapeutics. also show dose-dependent reduction electrical activity mean firing rate paclitaxel. compared outgrowth cortical (iCell® Neurons) (Peri.4U) cisplatin, paclitaxel vincristine. Goshajinkigan, Japanese herbal neuroprotectant medicine, was protective against paclitaxel-induced neurotoxicity but phenotypes. Thus, have demonstrated useful distinguish drug class studies potential prevention chemotherapy-induced