2018 Fiscal Year Final Research Report

Contraction of wild-life iHep cell and development of the evaluation method for metabolism of the top predator

Research Project

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Project/Area Number	17K20038
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Research Field	Environmental analyses and evaluation and related fields
Research Institution	Hokkaido University
Principal Investigator	Ikenaka Yoshinori 北海道大学, 獣医学研究院, 准教授 (40543509)
Co-Investigator(Kenkyū-buntansha)	川合佑典帯広畜産大学, 畜産学部, 助教 (10709546) 鈴木淳史九州大学, 生体防御医学研究所, 教授 (30415195) 三谷曜子北海道大学, 北方生物圏フィールド科学センター, 准教授 (40538279) 石塚真由美北海道大学, 獣医学研究院, 教授 (50332474) 水川葉月愛媛大学, 農学研究科, 准教授 (60612661) 中山翔太北海道大学, 獣医学研究院, 助教 (90647629)
Project Period (FY)	2017-06-30 – 2019-03-31
Keywords	野生動物 / iHep / Metabolism / トッププレデター / P450 / UGT / SULT
Outline of Final Research Achievements	The purpose of this study is to develop the evaluation method of metabolism, which is the key to chemical sensitivity, and to clarify the chemical metabolic ability of rare top predator. Fresh liver is required for the evaluation of metabolism, but rare species are difficult to obtain. Therefore, in this study, we attempted to differentiate and induce liver-like cells (iHep cells) from skin fibroblasts by direct reprogramming. First, as a result of this study, we succeeded in culturing fibroblasts of several top predators such as brown bear and Sea lion. Furthermore, as a result of attempting to induce iHep cells using cultured fibroblasts, it was found that the cells were transformed into epithelial cells expressing albumin by introducing a specific factor. In this study, it is highly probable that iHep cells were successfully generated starting from wild animals.
Free Research Field	環境毒性学
Academic Significance and Societal Importance of the Research Achievements	トッププレデターの化学物質感受性を適切に評価できる実験系は無く、その評価法を確立する必要があった。本研究で一部誘導に成功した野生動物iHep細胞は、野生動物の化学物質感受性を非侵襲的かつ迅速に実施できる。更に、iHep細胞は様々な野生動物獣医療にも応用可能である。例えば、投薬や麻酔による不動化の初期スクリーニングに応用する事で、経験則では無く、科学的根拠に基づいた投与doseの決定が可能となる。これにより、獣医療現場における麻酔中の死亡事故などの減少に通じるだけでなく、将来的には各動物種に応じた創薬への応用も期待できる。