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
Processing time: 403 Days and 6.7 Hours
Abstract
BACKGROUND

Liver transplantation is a therapy for irreversible liver failure; however, at present, donor organs are in short supply. Cell transplantation therapy for liver failure is still at the developmental stage and is critically limited by a shortage of human primary hepatocytes.

AIM

To investigate the possibility that hepatic progenitor cells (HPCs) prepared from the portal branch-ligated hepatic lobe may be used in regenerative medicine, we attempted to enable the implantation of extracellular matrices containing organoids consisting of HPC-derived hepatocytes and non-parenchymal cells.

METHODS

In vitro liver organoid tissue has been generated by accumulating collagen fibrils, fibroblasts, and HPCs on a mesh of polylactic acid fabric using a bioreactor; this was subsequently implanted into syngeneic wild-type mice.

RESULTS

The in vitro liver organoid tissues generated transplantable tissues in the condensed collagen fibril matrix and were obtained from the mouse through partial hepatectomy.

CONCLUSION

Liver organoid tissue was produced from expanded HPCs using an originally designed bioreactor system. This tissue was comparable to liver lobules, and with fibroblasts embedded in the network collagen fibrils of this artificial tissue, it is useful for reconstructing the hepatic interstitial structure.

Keywords: Liver; Three-dimensional tissue culture; Hepatic progenitor cells; Angiogenesis; Biomimetic extracellular matrix

Core Tip: Liver transplantation is a therapeutic procedure used to recover liver function in patients with irreversible liver failure; however, there is presently a shortage of transplant organs available. Hepatic stem and progenitor cells are expected to allow regenerative medicine to produce a cell source as an alternative to whole organs. The portal branch-ligated, 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 mice. This portal branch-ligated-derived HPC line has the potential to proliferate, mature, and form implantable hepatic tissue.