Abstract: Canine neurological diseases are broadly classified into those originating primarily from the central nervous system and those from the peripheral nervous system. Peripheral nerve diseases, affecting both sensory and motor nerves, are categorized based on their pathogenesis such as traumatic, infectious, inflammatory, neoplastic, or degenerative origins, and result in a variety of clinical signs. In particular, sensory nerve disorders cause abnormal sensations and pain, which are more challenging to diagnose in animals like dogs than in humans due to the difficulty in communicating their subjective symptoms. In terms of treatment, while inflammatory diseases can often be treated aggressively with immunosuppressants, peripheral nerve diseases caused by other factors are primarily managed with physical therapy, as there are few effective medications available other than analgesics. To address these challenges, basic research aimed at developing therapeutic drugs and methods for early diagnosis is crucial. However, the lack of a stable in vitro experimental system using canine peripheral nerves has hindered such research and development. We have attempted to obtain functional canine peripheral nerves derived from iPS cells by combining our proprietary animal iPS cell-technology (Yoshimatsu et al., Stem Cell Research, 2021) with an efficient differentiation method for generating peripheral neurons from human iPS cells via neural crest cells (Kamiya et al., NPJ regenerative medicine, 2022). In this presentation, we will share the latest findings, including: 1) Induction of canine iPS cells into peripheral/sensory neurons via neural crest cells, 2) Gene expression patterns during differentiation and maturation, 3) Functional analysis of these peripheral/sensory neurons. Additionally, we propose the potential application of our canine iPSC-derived in vitro peripheral/sensory nerves evaluation system.
