title: Hepatic differentiation of mouse embryonic stem cells and induced pluripotent stem cells during organoid formation in hollow fibers.
abstract: We have focused on pluripotent stem cells as a potential source of a hybrid-type artificial liver (HAL) and tried to develop a method for differentiating the pluripotent stem cells into cells of a hepatic lineage. In this study, we investigated the hepatic differentiation of mouse embryonic stem (ES) cells and induced pluripotent stem (iPS) cells by applying hollow fiber (HF)/organoid culture method, in which cultured cells form a cellular aggregate called an "organoid" in the lumen of the HF. ES and iPS cells were injected into HFs to induce organoid formation, and cells were cultured. To induce hepatic differentiation, we added differentiation-promoting agents to the culture medium. The expression levels of differentiation-related genes were up-regulated, with cell proliferation and organoid formation inside HFs. Since we were able to achieve a high cell density in culture, the maximum levels of liver-specific functions per unit volume in the differentiating ES and iPS cells reached a level comparable to or better than that of primary mouse hepatocytes. In conclusion, ES and iPS cells have the potential to be a cell source for a HAL, and the HF/organoid culture method, therefore, has promise as a basic technology for the development of a HAL.
authors: Department of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan.
authors: Naoki
authors: N
authors: Amimoto
authors: Hiroshi
authors: H
authors: Mizumoto
authors: Kohji
authors: K
authors: Nakazawa
authors: Hiroyuki
authors: H
authors: Ijima
authors: Kazumori
authors: K
authors: Funatsu
authors: Toshihisa
authors: T
authors: Kajiwara
mesh_terms: D000418:Albumins / Q000378:metabolism; D000641:Ammonia; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D048430:Cell Shape; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000235:genetics; D009940:Organoids / Q000166:cytology* / Q000378:metabolism; D046509:Tissue Culture Techniques / Q000379:methods*
chemical_list: D000418:Albumins; D008567:Membranes, Artificial; D000641:Ammonia