In vitro assessment of canine tissue stem cells or iPS-derived hepatocyte-like cells to investigate their potential in drug metabolism evaluation

Research Project

Project/Area Number	25850214
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Veterinary medical science
Research Institution	Azabu University
Principal Investigator	Neo Sakurako 麻布大学, 獣医学部, 助教 (50532107)
Research Collaborator	AKAIKE Toshihiro 東京工業大学, 大学院生命理工学研究科, 名誉教授 KUTSUZAWA Koichi 東京理科大学, 総合研究機構, ポストドクトラル研究員 ORITO Kensuke 麻布大学, 獣医学科, 教授
Project Period (FY)	2013-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	肝再生 / 犬 / 胎盤抽出液 / 長期培養 / 骨髄 / 骨髄細胞 / 肝臓 / 三次元化 / 薬物代謝 / 肝細胞 / 分化誘導
Outline of Final Research Achievements	For the purpose of reducing animal testing and to construct an alternative method to animal testing in drug discovery research, we designed a basic investigation to create drug screening chips using induced hepatocyte-like cells (iHep). Tissue stem cells were used to induce hepatocyte-like cells which could be maintained over a long period, with preservation of differentiated functions. Canine bone marrow was used for the cell source and was cultured with human placental hydrolysate in order to induce hepatocyte-like cells. Contrary to expectations, iHep retained expression of hepatocyte specific markers in mRNA and protein, and maintained lipid and drug metabolism for more than 2 months. In conclusion, bone marrow derived iHeps are a potential source for drug screening chips.