Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2022; 28(19): 2100-2111
Published online May 21, 2022. doi: 10.3748/wjg.v28.i19.2100
Ultrastructural changes in porcine liver sinusoidal endothelial cells of machine perfused liver donated after cardiac death
Hiroki Bochimoto, Yo Ishihara, Nur Khatijah Mohd Zin, Hiroyoshi Iwata, Daisuke Kondoh, Hiromichi Obara, Naoto Matsuno
Hiroki Bochimoto, Nur Khatijah Mohd Zin, Department of Cell Physiology, The Jikei University School of Medicine, Minato-ku 105-8461, Tokyo, Japan
Hiroki Bochimoto, Yo Ishihara, Hiromichi Obara, Naoto Matsuno, Department of Transplantation Technology and Therapeutic Development, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
Hiroyoshi Iwata, Naoto Matsuno, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
Daisuke Kondoh, Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Hokkaido, Japan
Hiromichi Obara, Department of Mechanical Engineering, Tokyo Metropolitan University, Hachioji 192-0397, Tokyo, Japan
Author contributions: Bochimoto H and Ishihara Y contributed equally to this work; Bochimoto H, Obara H and Matsuno N designed and coordinated the study; Bochimoto H, Ishihara Y, Kondoh D, Obara H and Matsuno N performed the experiments, acquired and analyzed data; Bochimoto H, Ishihara Y, Mohd Zin NK, Iwata H, Kondoh D, Obara H and Matsuno N interpreted the data; Bochimoto H wrote the manuscript; all authors approved the final version of the article.
Supported by JSPS KAKENHI Grant, No. JP17K10503 (to Matsuno N) and JP20K11539 (to Bochimoto H).
Institutional review board statement: The study was reviewed and approved by the Institutional Animal Ethics Committee of the Clinical Research Center, Asahikawa Medical University.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (permit No. 14172, The Institutional Animal Ethics Committee of the Clinical Research Center, Asahikawa Medical University, Asahikawa, Japan).
Conflict-of-interest statement: All of the authors have nothing to disclose.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hiroki Bochimoto, MD, PhD, Assistant Professor, Department of Cell Physiology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku 105-8461, Tokyo, Japan. botimoto@jikei.ac.jp
Received: May 19, 2021
Peer-review started: May 19, 2021
First decision: June 12, 2021
Revised: July 17, 2021
Accepted: April 3, 2022
Article in press: April 3, 2022
Published online: May 21, 2022
Processing time: 362 Days and 17.3 Hours
Abstract
BACKGROUND

The machine perfusion (MP) preservation including hypothermic MP (HMP) and midthermic MP (MMP) has been considered as a promising strategy to preserve the functions of liver donated after cardiac death. The importance of understanding liver sinusoidal endothelial cells (LSEC) damage in regulating liver injury during MP has been emphasized. However, the ultrastructural changes in the LSEC and sinusoids around them after MP are unclear.

AIM

To investigate the ultrastructural changes in the LSEC and sinusoids around them after MP.

METHODS

Porcine liver grafts undergo a warm ischemia time of 60 minutes perfused for 4 h with modified University of Wisconsin gluconate solution. Group A grafts were preserved with HMP at 8 °C constantly for 4 h. Group B grafts were preserved with a rewarming solution at 22 °C by MMP for 4 h. Then the ultrastructural changes in the LSEC and sinusoids in Group A and B were comparatively analyzed by using osmium-maceration scanning electron microscopy with complementary transmission electron microscopy methods.

RESULTS

An analysis of the LSEC after warm ischemia revealed that mitochondria with condensed-shaped cristae, abnormal vesicles, reduction of ribosomes and the endoplasmic reticulum (ER) surround the mitochondria appeared. The MP subsequent after warm ischemia alleviate the abnormal vesicles and reduction of ribosomes in LSEC, which indicated the reduction of the ER damage. However, MMP could restore the tubular mitochondrial cristae, while after HMP the condensed and narrow mitochondrial cristae remained. In addition, the volume of the sinusoidal space in the liver grafts after MMP were restored, which indicated a lower risk of pressure injury than HMP.

CONCLUSION

MMP alleviates the ER damage of LSEC by warm ischemia, additionally restore the metabolism of LSEC via the normalization of mitochondria and prevent the share stress damage of liver grafts.

Keywords: Liver; Sinusoidal endothelial cells; Warm ischemia; Machine perfusion preservation; Transplantation; Ultrastructure

Core Tip: The importance of understanding liver sinusoidal endothelial cells (LSEC) damage in regulating liver injury during machine perfusion (MP) preservation has been emphasized. Here, we comparatively analyzed the ultrastructural changes in the LSEC and sinusoids around them at four hours after hypothermic MP (HMP) or midthermic MP (MMP). MP alleviated the ER damage of LSEC caused by warm ischemia. Moreover, MMP temperature conditions restore the metabolism of LSEC via the normalization of cristae of mitochondria and prevent the damage of the liver graft by share stress.