Decellularized Organ-Derived Scaffold Is a Promising Carrier for Human Induced Pluripotent Stem Cells-Derived Hepatocytes
Hideaki Kojima,
Hiroshi Yagi,
Hiroko Kushige,
Yukiko Toda,
Kazuo Takayama,
Shinako Masuda,
Toshinori Morisaku,
Tomonori Tsuchida,
Kohei Kuroda,
Kazuya Hirukawa,
Jumpei Inui,
Kotaro Nishi,
Yutaka Nakano,
Masayuki Tanaka,
Shutaro Hori,
Yasushi Hasegawa,
Yuta Abe,
Minoru Kitago,
Shungo Adachi,
Masatoshi Tomi,
Katsuhisa Matsuura,
Hiroyuki Mizuguchi,
Yuko Kitagawa
Affiliations
Hideaki Kojima
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Hiroshi Yagi
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Hiroko Kushige
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Yukiko Toda
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Japan
Kazuo Takayama
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Japan
Shinako Masuda
Institute of Advanced BioMedical Engineering and Science, Tokyo Women’s Medical University, Shinjuku 162-8666, Japan
Toshinori Morisaku
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Tomonori Tsuchida
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Kohei Kuroda
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Kazuya Hirukawa
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Jumpei Inui
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Japan
Kotaro Nishi
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Yutaka Nakano
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Masayuki Tanaka
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Shutaro Hori
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Yasushi Hasegawa
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Yuta Abe
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Minoru Kitago
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Shungo Adachi
Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Aomi 2-4-7, Koto 162-8666, Japan
Masatoshi Tomi
Division of Pharmaceutics, Faculty of Pharmacy, Keio University, Shibakoen 1-5-30, Minato 162-8666, Japan
Katsuhisa Matsuura
Institute of Advanced BioMedical Engineering and Science, Tokyo Women’s Medical University, Shinjuku 162-8666, Japan
Hiroyuki Mizuguchi
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Japan
Yuko Kitagawa
Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku 162-8666, Japan
Human induced pluripotent stem cells (hiPSCs) are a promising cell source for elucidating disease pathology and therapy. The mass supply of hiPSC-derived cells is technically feasible. Carriers that can contain a large number of hiPSC-derived cells and evaluate their functions in vivo-like environments will become increasingly important for understanding disease pathogenesis or treating end-stage organ failure. hiPSC-derived hepatocyte-like cells (hiPSC-HLCs; 5 × 108) were seeded into decellularized organ-derived scaffolds under circumfusion culture. The scaffolds were implanted into immunodeficient microminiature pigs to examine their applicability in vivo. The seeded hiPSC-HLCs demonstrated increased albumin secretion and up-regulated cytochrome P450 activities compared with those in standard two-dimensional culture conditions. Moreover, they showed long-term survival accompanied by neovascularization in vivo. The decellularized organ-derived scaffold is a promising carrier for hiPSC-derived cells for ex vivo and in vivo use and is an essential platform for regenerative medicine and research.
