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

doi:10.3748/wjg.v28.i19.2100

Ultrastructural changes in porcine liver sinusoidal endothelial cells of machine perfused liver donated after cardiac death

World J Gastroenterol. 2022 May 21;28(19):2100-2111. doi: 10.3748/wjg.v28.i19.2100.

Authors

Hiroki Bochimoto¹, Yo Ishihara², Nur Khatijah Mohd Zin¹, Hiroyoshi Iwata³, Daisuke Kondoh⁴, Hiromichi Obara², Naoto Matsuno²

Affiliations

¹ Department of Cell Physiology, The Jikei University School of Medicine, Minato-ku 105-8461, Tokyo, Japan.
² Department of Transplantation Technology and Therapeutic Development, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan.
³ Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan.
⁴ Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Hokkaido, Japan.

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; Machine perfusion preservation; Sinusoidal endothelial cells; Transplantation; Ultrastructure; Warm ischemia.

MeSH terms

Animals
Death
Endothelial Cells
Humans
Liver / metabolism
Organ Preservation Solutions* / pharmacology
Organ Preservation* / methods
Perfusion / methods
Swine

Substances

Organ Preservation Solutions