Long-term self-renewal of human ES/iPS-derived hepatoblast-like cells on human laminin 111-coated dishes

人类 ES/iPS 衍生的肝母细胞样细胞在人层粘连蛋白 111 包被的培养皿中的长期自我更新

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作者:Kazuo Takayama, Yasuhito Nagamoto, Natsumi Mimura, Katsuhisa Tashiro, Fuminori Sakurai, Masashi Tachibana, Takao Hayakawa, Kenji Kawabata, Hiroyuki Mizuguchi

Abstract

The establishment of self-renewing hepatoblast-like cells (HBCs) from human pluripotent stem cells (PSCs) would realize a stable supply of hepatocyte-like cells for medical applications. However, the functional characterization of human PSC-derived HBCs was not enough. To purify and expand human PSC-derived HBCs, human PSC-derived HBCs were cultured on dishes coated with various types of human recombinant laminins (LN). Human PSC-derived HBCs attached to human laminin-111 (LN111)-coated dish via integrin alpha 6 and beta 1 and were purified and expanded by culturing on the LN111-coated dish, but not by culturing on dishes coated with other laminin isoforms. By culturing on the LN111-coated dish, human PSC-derived HBCs were maintained for more than 3 months and had the ability to differentiate into both hepatocyte-like cells and cholangiocyte-like cells. These expandable human PSC-derived HBCs would be manageable tools for drug screening, experimental platforms to elucidate mechanisms of hepatoblasts, and cell sources for hepatic regenerative therapy.

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