title: Efficient recellularisation of decellularised whole-liver grafts using biliary tree and foetal hepatocytes.
abstract: A whole-organ regeneration approach, using a decellularised xenogeneic liver as a scaffold for the construction of a transplantable liver was recently reported. Deriving suitable scaffolds was the first step towards clinical application; however, effective recellularisation remains to be achieved. This report presents a strategy for the improvement of the recellularisation process, using novel cell-seeding technique and cell source. We evaluated recellularised liver grafts repopulated through the portal vein or the biliary duct with mice adult hepatocytes or E14.5 foetal hepatocytes. More than 80% of the cells seeded through the biliary tree entered the parenchyma beyond the ductule-lining matrix barrier and distributed throughout the liver lobule. In contrast, about 20% of the cells seeded through the portal tree entered the parenchyma. The gene expression levels of foetal hepatocyte albumin, glucose 6-phosphatase, transferrin, cytokeratin 19, and gamma-glutamyl transpeptidase were increased in three-dimensional cultures in the native liver-derived scaffolds, and the activation of liver detoxification enzymes and formation of biliary duct-like structures were supported. The metabolic functions of liver grafts recellularised with different cell types were similar. These results suggest that biliary tree cell-seeding approach is promising, and that liver progenitor cells represent a good cell source candidate.
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Satoshi
authors: S
authors: Ogiso
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Kentaro
authors: K
authors: Yasuchika
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Ken
authors: K
authors: Fukumitsu
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Takamichi
authors: T
authors: Ishii
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Hidenobu
authors: H
authors: Kojima
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Yuya
authors: Y
authors: Miyauchi
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Ryoya
authors: R
authors: Yamaoka
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Junji
authors: J
authors: Komori
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Hokahiro
authors: H
authors: Katayama
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Takayuki
authors: T
authors: Kawai
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Elena Yukie
authors: EY
authors: Yoshitoshi
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Sadahiko
authors: S
authors: Kita
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Katsutaro
authors: K
authors: Yasuda
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Shinji
authors: S
authors: Uemoto
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D053539:Keratin-19 / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D000072356:Parenchymal Tissue / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D054457:Tissue Scaffolds; D061250:Transferrins / Q000378:metabolism; D014183:Transplantation, Heterologous; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D053539:Keratin-19; D061250:Transferrins; D005723:gamma-Glutamyltransferase; D005952:Glucose-6-Phosphatase