Development and assessment of new risk assessment methods
Title of Research:
17_PT01-01

Chip device for in vitro systemic toxicology
Principal Investigator:
Junji Fukuda, PhD (Professor, Yokohama National University, Engineering)79-5 Tokiwadai, Hodogaya, Yokohama, Kanagawa, 240-8501, Japan(tel) +81-045-339-4008, (e-mail) fukuda@ynu.jp
Collaborators:
Kazutomo Iijima, PhD (Associate Professor, Yokohama National University, Engineering)79-5 Tokiwadai, Hodogaya, Yokohama, Kanagawa, 240-8501, Japan
Yasunari Kanda, PhD (Head of Cardiac pharmacology, National Institute of Health Sciences,Division of Pharmacology)
3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan
Yusuke Okubo, PhD (Senior staff scientist, National Institute of Health Sciences, Division ofCellular and Molecular Toxicology)
3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan
Kiyomi Ohmori, PhD (Adjunct Professor, Yokohama National University, Research Initiatives andPromotion Organization)
79-5 Tokiwadai, Hodogaya, Yokohama, Kanagawa, 240-8501, Japan
Summary of Research:
Body-on-a-chip has emerged as a novel approach for Alternatives to Animal Testing. The aim of
this study is to develop a body-on-a-chip for in vitro drug testing to evaluate systemic toxicity ofchemicals. In our chip devices, several tissues including the liver, the cardiac tissue, and the small
intestine were fabricated as either cell layer tissues or spherical tissues to replicate in vivo kinetics
and interactions. One of our results showed that improved oxygen supply and a selection ofenergy metabolisms significantly matured human iPS-derived cardiomyocyte spheroids. Changes
in beating of these spheroids were characterized using cell motion imaging on the chip device,indicating that this can be an important toxicity testing. In addition, human iPS cell-based signaling
reporter system was also developed for prediction of chemical teratogenicity.
Timeline:
March 1, 2019 - February 29, 2020
Topics:Poster presentation at JCIA LRI Annual Workshop 2019 “Chip devices for in vitro systemic
toxicology” (Tokyo, August 30th, 2019)
Publications:
1. Y. Sawada, Y. Miura, E. Kobayashi, K. Iijima, J. Fukuda, H. Itagaki, “Evaluating
immunotoxicity in co-culture system of THP-1 and undifferentiated / keratinized NHEK”, The
46th Annual Meeting of The Japanese Society of Toxicology, Tokushima, Japan, June 2019
2. T. Shinagawa, J. Fukuda, S. Toyama, J. Fujita, K. Fukuda, Y. Kanda, A. Satsuka, “Maturationof human iPS-derived cardiomyocytes on oxygen-permeable spheroid culture device”,
Yokohama Branch Meeting of Society for Chemical Engineers, Yokohama, Japan, August2019
3. T. Usui, D. Qin, J. Fukuda, “Co-culture of CACO-2 cell sheets and E. coli-encapsulated
microbeads for in vitro intestine model”, APCChE2019, Sapporo, September 2019
4. Y. Yamamura, J. Fukuda, “Drug evaluation chip device using multiple 3D tissue models”, The
32nd Annual Meeting of the Japanese Society for Alternatives to Animal Experiments,Tsukuba, Japan, November 2019
5. D. Qin, T. Usui, J. Fukuda, “Co-culture of intestinal epithelial cells and bacteria-embedded
beads for in vitro small intestine model”, The 32nd Annual Meeting of the Japanese Society
for Alternatives to Animal Experiments, Tsukuba, Japan, November 2019