Decellularized Organ-Derived Scaffold Is a Promising Carrier for Human Induced Pluripotent Stem Cells-Derived Hepatocytes

Author:

Kojima Hideaki,Yagi HiroshiORCID,Kushige Hiroko,Toda Yukiko,Takayama Kazuo,Masuda Shinako,Morisaku Toshinori,Tsuchida Tomonori,Kuroda Kohei,Hirukawa Kazuya,Inui Jumpei,Nishi KotaroORCID,Nakano Yutaka,Tanaka Masayuki,Hori Shutaro,Hasegawa YasushiORCID,Abe Yuta,Kitago MinoruORCID,Adachi ShungoORCID,Tomi Masatoshi,Matsuura Katsuhisa,Mizuguchi Hiroyuki,Kitagawa Yuko

Abstract

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.

Funder

Japan Agency for Medical Research and Development

Publisher

MDPI AG

Subject

General Medicine

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