Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

Takayama, Kazuo; Akita, Naoki; Mimura, Natsumi; Akahira, Rina; Taniguchi, Yukimasa; Ikeda, Makoto; Sakurai, Fuminori; Ohara, Osamu; Morio, Tomohiro; Sekiguchi, Kiyotoshi; Mizuguchi, Hiroyuki

doi:https://doi.org/10.1002/hep4.1111

Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

Takayama, Kazuo; Akita, Naoki; Mimura, Natsumi et al.

Hepatology Communications, 2017, 1(10), 1058-1069

Number of Access:1,377（2025-08-18 14:24 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/71807

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Title	Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine
Creator	NRID 1000010759509 1000010759509 CreatorName Takayama, Kazuo
	CreatorName Akita, Naoki
	CreatorName Mimura, Natsumi
	CreatorName Akahira, Rina
	CreatorName Taniguchi, Yukimasa
	CreatorName Ikeda, Makoto
	NRID 1000070370939 1000070370939 researchmap permalink read0165081 read0165081 Scopus Author ID 7003748169 7003748169 CreatorName Sakurai, Fuminori
	NRID 1000020370926 1000020370926 CreatorName Ohara, Osamu
	NRID 1000030239628 1000030239628 CreatorName Morio, Tomohiro
	NRID 1000050187845 1000050187845 researchmap permalink read0054833 read0054833 Scopus Author ID 7201662709 7201662709 ORCID 0000-0002-6433-1410 0000-0002-6433-1410 CreatorName Sekiguchi, Kiyotoshi
	NRID 1000050311387 1000050311387 researchmap permalink read0165079 read0165079 Scopus Author ID 57195381326 57195381326 CreatorName Mizuguchi, Hiroyuki
Description	Kazuo Takayama, Naoki Akita, Natsumi Mimura, Rina Akahira, Yukimasa Taniguchi, Makoto Ikeda, Fuminori Sakurai, Osamu Ohara, Tomohiro Morio, Kiyotoshi Sekiguchi and Hiroyuki Mizuguchi "Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine", Hepatology Communications, Vol. 1 (10) 1058–1069, Wiley, 2017
Abstract	Hepatocyte‐like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells are expected to be applied for regenerative medicine. In this study, we attempted to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation. First, human iPS‐HLCs were generated from a human leukocyte antigen‐homozygous donor on the assumption that the allogenic transplantation might be carried out. Highly efficient hepatocyte differentiation was performed under a feeder‐free condition using human recombinant laminin 111, laminin 511, and type IV collagen. The percentage of asialoglycoprotein receptor 1‐positive cells was greater than 80%, while the percentage of residual undifferentiated cells was approximately 0.003%. In addition, no teratoma formation was observed even at 16 weeks after human iPS‐HLC transplantation. Furthermore, harmful genetic somatic single‐nucleotide substitutions were not observed during the hepatocyte differentiation process. We also developed a cryopreservation protocol for hepatoblast‐like cells without negatively affecting their hepatocyte differentiation potential by programming the freezing temperature. To evaluate the therapeutic potential of human iPS‐HLCs, these cells (1 × 106 cells/mouse) were intrasplenically transplanted into acute liver injury mice treated with 3 mL/kg CCl4 only once and chronic liver injury mice treated with 0.6 mL/kg CCl4 twice weekly for 8 weeks. By human iPS‐HLC transplantation, the survival rate of the acute liver injury mice was significantly increased and the liver fibrosis level of chronic liver injury mice was significantly decreased. Conclusion: We were able to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation.
Publisher	Wiley
Source Title	Hepatology Communications
Volume (Issue)	1(10)
Page	1058-1069
Date of Issued	2017-10
Language	English
Handle URL	https://hdl.handle.net/11094/71807
eISSN	2471254X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1002/hep4.1111
Access Rights	open access
CopyRight	© 2017 The Authors. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Hepatology Communications. 2017, 1(10), p. 1058-1069
DC.title	Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine
DC.creator	Takayama, Kazuo
	Akita, Naoki
	Mimura, Natsumi
	Akahira, Rina
	Taniguchi, Yukimasa
	Ikeda, Makoto
	Sakurai, Fuminori
	Ohara, Osamu
	Morio, Tomohiro
	Sekiguchi, Kiyotoshi
	Mizuguchi, Hiroyuki
DC.publisher	Wiley
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2017-10
DC.identifier	https://doi.org/10.1002/hep4.1111
DC.description	Kazuo Takayama, Naoki Akita, Natsumi Mimura, Rina Akahira, Yukimasa Taniguchi, Makoto Ikeda, Fuminori Sakurai, Osamu Ohara, Tomohiro Morio, Kiyotoshi Sekiguchi and Hiroyuki Mizuguchi "Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine", Hepatology Communications, Vol. 1 (10) 1058–1069, Wiley, 2017
DCTERMS.abstract	Hepatocyte‐like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells are expected to be applied for regenerative medicine. In this study, we attempted to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation. First, human iPS‐HLCs were generated from a human leukocyte antigen‐homozygous donor on the assumption that the allogenic transplantation might be carried out. Highly efficient hepatocyte differentiation was performed under a feeder‐free condition using human recombinant laminin 111, laminin 511, and type IV collagen. The percentage of asialoglycoprotein receptor 1‐positive cells was greater than 80%, while the percentage of residual undifferentiated cells was approximately 0.003%. In addition, no teratoma formation was observed even at 16 weeks after human iPS‐HLC transplantation. Furthermore, harmful genetic somatic single‐nucleotide substitutions were not observed during the hepatocyte differentiation process. We also developed a cryopreservation protocol for hepatoblast‐like cells without negatively affecting their hepatocyte differentiation potential by programming the freezing temperature. To evaluate the therapeutic potential of human iPS‐HLCs, these cells (1 × 106 cells/mouse) were intrasplenically transplanted into acute liver injury mice treated with 3 mL/kg CCl4 only once and chronic liver injury mice treated with 0.6 mL/kg CCl4 twice weekly for 8 weeks. By human iPS‐HLC transplantation, the survival rate of the acute liver injury mice was significantly increased and the liver fibrosis level of chronic liver injury mice was significantly decreased. Conclusion: We were able to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation.
DC.rights	© 2017 The Authors. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	71807
citation_title	Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine
citation_author	Takayama, Kazuo
	Akita, Naoki
	Mimura, Natsumi
	Akahira, Rina
	Taniguchi, Yukimasa
	Ikeda, Makoto
	Sakurai, Fuminori
	Ohara, Osamu
	Morio, Tomohiro
	Sekiguchi, Kiyotoshi
	Mizuguchi, Hiroyuki
citation_publisher	Wiley
citation_language	English
citation_date	2017-10
citation_journal_title	Hepatology Communications
citation_volume	1
citation_issue	10
citation_firstpage	1058
citation_lastpage	1069
citation_doi	https://doi.org/10.1002/hep4.1111
citation_public_url	https://hdl.handle.net/11094/71807

Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

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