Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2022; 28(14): 1444-1454
Published online Apr 14, 2022. doi: 10.3748/wjg.v28.i14.1444
Syngeneic implantation of mouse hepatic progenitor cell-derived three-dimensional liver tissue with dense collagen fibrils
Miho Tamai, Eijiro Adachi, Masaya Kawase, Yoh-ichi Tagawa
Miho Tamai, Yoh-ichi Tagawa, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama-shi 226-8501, Japan
Miho Tamai, Faculty of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
Eijiro Adachi, Department of Molecular Morphology, Kitasato University, Yokohama-shi 319-3526, Japan
Eijiro Adachi, Long-Term Care Health Facility Yasuragi, Ibaraki Zip or Postal Code, Japan
Masaya Kawase, Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan
Author contributions: Tagawa YI designed the study; Tamai M conducted all experiments; Kawase M performed statistical processing; Adachi E and Tagawa YI supervised the project; Tamai M and Tagawa YI wrote the manuscript; all authors read and approved the manuscript.
Supported by Grants-in-Aid for Scientific Research (A), No. 25242040 (to Tagawa YI); Grants-in-Aid for Challenging Exploratory Research, No. 20K21520 (to Tagawa YI); Grants-in-Aid for Early Career Scientists from the Japan Society for the Promotion of Science (JSPS), No. 19K20655 (to Tamai M); Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), No. 231190003 (to Tagawa YI); Japan Agency for Medical Research and Development (AMED), No. 20fk0310102 (to Tagawa YI); and Building of Consortia for the Development of Human Resources in Science and Technology, Ministry of Education, Culture, Sports, Science and Technology, Japan (to Tamai M).
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals. All animal experiments were conducted in accordance with policies of the Animal Experimentation Committee of the Tokyo Institute of Technology Guide for the Care and Use of Laboratory Animals. Specific protocols used in this study were approved by the Animal Experimentation Committee of the Tokyo Institute of Technology (approved protocols are D2015009, D2012019 and 2009024-5).
Conflict-of-interest statement: The authors declare no conflict of interest relevant to this manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yoh-ichi Tagawa, DSc, Associate Professor, School of Life Science and Technology, Tokyo Institute of Technology, 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama-shi 226-8501, Japan. ytagawa@bio.titech.ac.jp
Received: February 27, 2021
Peer-review started: February 27, 2021
First decision: March 28, 2021
Revised: April 10, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: April 14, 2022
ARTICLE HIGHLIGHTS
Research background

Liver transplantation is a therapeutic procedure to recover liver function in patients with irreversible liver failure; however, there is currently a shortage of available transplant organs, which limits the availability of this treatment.

Research motivation

Portal branch-ligated (PBL) HPCs are expected to allow regenerative medicine to produce a cell source to provide an alternate source for transplantation.

Research objectives

We aimed to development a liver model using HPCs.

Research methods

Hepatic stem/progenitor cells have the ability to multiply ex vivo and differentiate into hepatocytes and cholangiocytes. We have previously established HPC lines derived from the hepatic tissues of mice after ligation of venous drainage. In this study, the PBL hepatic lobe-derived HPCs multiplied in a bioreactor chamber to form liver organoid tissues comparable to liver lobules. These organoid tissues were implanted into syngeneic wild-type mice.

Research results

In the three-dimensional (3-D) liver tissue culture model, PBL-HPCs differentiated into mature hepatocyte-like cells, in binuclear populations, and with a bile duct–like structure. Quantitative real-time polymerase chain reaction analysis revealed that the cells expressed hepatocyte differentiation markers. In the 3-D liver tissue culture model derived from PBL-HPCs, the levels of urea and albumin production and activities of Cytochrome P450 enzymes were gradually enhanced.

Research conclusions

By mimicking the structure of the natural liver, our system was effective for the construction of a functional liver tissue model.

Research perspectives

This PBL-derived HPC line has the potential to proliferate, mature, and form implantable hepatic tissue.