title: Formation of three-dimensional hepatic tissue by the bottom-up method using spheroids.
abstract: Liver regenerative medicine has attracted attention as a possible alternative to organ transplantation. To address the challenge of liver regenerative medicine, the development of a construction method has been proposed for liver tissue in vitro with a high cell density and high functionality for transplantation into patients with severe liver failure. In this study, we fabricated highly functional three-dimensional hepatic tissue by a bottom-up method using spheroids. The hepatic tissue was formed by stacking hepatocyte spheroids covered with human umbilical vein endothelial cells (HUVECs). Hepatic tissue constructs were evaluated for cell survival, liver-specific functions, and histologically. As a result, we identified improvements in liver-specific functions (ammonia removal and albumin secretion) and cell survival. In addition, HUVECs were regularly distributed at every 100 μm within the tissue, and live cells were present within the whole tissue construct throughout the culture period. In summary, we successfully fabricated highly functional hepatic tissue by the bottom-up method using HUVEC-covered hepatocyte spheroids.
authors.affiliation: Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okudaira
authors.affiliation: Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Amimoto
authors.affiliation: Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizumoto
authors.affiliation: Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. Electronic address: kajiwara@chem-eng.kyushu-u.ac.jp.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kajiwara
mesh_terms: D000418:Albumins / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D022781:Hepatocytes / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000033:anatomy & histology / Q000166:cytology* / Q000502:physiology*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044968:Regenerative Medicine / Q000379:methods; D018874:Spheroids, Cellular / Q000166:cytology* / Q000637:transplantation
chemical_list: D000418:Albumins; D000641:Ammonia
keywords: Bottom-up method; Endothelial cell; Hepatocyte; Hollow fiber; Spheroid; Tissue cell culture; Tissue engineering