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Establishment of practical recellularized liver graft for blood perfusion using primary rat hepatocytes and liver sinusoidal endothelial cells
Author(s) -
Kojima Hidenobu,
Yasuchika Kentaro,
Fukumitsu Ken,
Ishii Takamichi,
Ogiso Satoshi,
Miyauchi Yuya,
Yamaoka Ryoya,
Kawai Takayuki,
Katayama Hokahiro,
YoshitoshiUebayashi Elena Yukie,
Kita Sadahiko,
Yasuda Katsutaro,
Sasaki Naoya,
Komori Junji,
Uemoto Shinji
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14666
Subject(s) - decellularization , medicine , perfusion , liver function , hepatocyte , pathology , sinusoid , microvessel , bile duct , biomedical engineering , tissue engineering , chemistry , immunohistochemistry , in vitro , biochemistry
Tissue decellularization produces a three‐dimensional scaffold that can be used to fabricate functional liver grafts following recellularization. Inappropriate cell distribution and clotting during blood perfusion hinder the practical use of recellularized livers. Here we aimed to establish a seeding method for the optimal distribution of parenchymal and endothelial cells, and to evaluate the effect of liver sinusoidal endothelial cells (LSECs) in the decellularized liver. Primary rat hepatocytes and LSECs were seeded into decellularized whole‐liver scaffolds via the biliary duct and portal vein, respectively. Biliary duct seeding provided appropriate hepatocyte distribution into the parenchymal space, and portal vein–seeded LSECs simultaneously lined the portal lumen, thereby maintaining function and morphology. Hepatocytes co‐seeded with LSECs retained their function compared with those seeded alone. Platelet deposition was significantly decreased and hepatocyte viability was maintained in the co‐seeded group after extracorporeal blood perfusion. In conclusion, our seeding method provided optimal cell distribution into the parenchyma and vasculature according to the three‐dimensional structure of the decellularized liver. LSECs maintained hepatic function, and supported hepatocyte viability under blood perfusion in the engineered liver graft owing to their antithrombogenicity. This recellularization procedure could help produce practical liver grafts with blood perfusion.