Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging

Li, Menglu; Ueyama-Toba, Yukiko; Lindley, Matthew; Kongklad, Gunganist; Nawa, Yasunori; Kumamoto, Yasuaki; Ishida, Seiichi; Kanda, Yasunari; Fujita, Satoshi; Mizuguchi, Hiroyuki; Fujita, Katsumasa

doi:https://doi.org/10.1021/acs.analchem.3c00976

Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging

Li, Menglu; Ueyama-Toba, Yukiko; Lindley, Matthew et al.

Analytical Chemistry, 2023, 95(24), 9252-9262

Number of Access:1,699（2026-11-12 09:47 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/103302

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
AnalChem_95_24_9252	pdf	None	4.06 MB	206	2025.12.05
AnalChem_95_24_9252_sup	pdf	None	3.77 MB	106	2025.12.05	Supporting Information

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging
Creator	CreatorName Li, Menglu
	NRID 1000010904930 1000010904930 ORCID 0000-0002-3491-7955 0000-0002-3491-7955 researchmap permalink toba-y toba-y CreatorName Ueyama-Toba, Yukiko
	CreatorName Lindley, Matthew
	CreatorName Kongklad, Gunganist
	CreatorName Nawa, Yasunori
	NRID 1000030611727 1000030611727 ORCID 0000-0002-4398-288X 0000-0002-4398-288X researchmap permalink jemappellekuma jemappellekuma Scopus Author ID 24376935000 24376935000 CreatorName Kumamoto, Yasuaki
	NRID 1000010270505 1000010270505 CreatorName Ishida, Seiichi
	NRID 1000070510387 1000070510387 CreatorName Kanda, Yasunari
	NRID 1000000392655 1000000392655 researchmap permalink read0120077 read0120077 Scopus Author ID 57193804976 57193804976 CreatorName Fujita, Satoshi
	NRID 1000050311387 1000050311387 researchmap permalink read0165079 read0165079 Scopus Author ID 57195381326 57195381326 ORCID 0000-0003-0594-8178 0000-0003-0594-8178 CreatorName Mizuguchi, Hiroyuki
	NRID 1000080362664 1000080362664 ORCID 0000-0002-2284-375X 0000-0002-2284-375X researchmap permalink read0089911 read0089911 Scopus Author ID 7404058829 7404058829 CreatorName Fujita, Katsumasa
Description	This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry 95, 9252 (2023), © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.analchem.3c00976.
Abstract	To promote the clinical application of human induced pluripotent stem cell (hiPSC)-derived hepatocytes, a method capable of monitoring regenerative processes and assessing differentiation efficiency without harming or modifying these cells is important. Raman microscopy provides a powerful tool for this as it enables label-free identification of intracellular biomolecules in live samples. Here, we used label-free Raman microscopy to assess hiPSC differentiation into hepatocyte lineage based on the intracellular chemical content. We contrasted these data with similar phenotypes from the HepaRG and from commercially available hiPSC-derived hepatocytes (iCell hepatocytes). We detected hepatic cytochromes, lipids, and glycogen in hiPSC-derived hepatocyte-like cells (HLCs) but not biliary-like cells (BLCs), indicating intrinsic differences in biomolecular content between these phenotypes. The data show significant glycogen and lipid accumulation as early as the definitive endoderm transition. Additionally, we explored the use of Raman imaging as a hepatotoxicity assay for the HepaRG and iCell hepatocytes, with data displaying a dose-dependent reduction of glycogen accumulation in response to acetaminophen. These findings show that the nondestructive and high-content nature of Raman imaging provides a promising tool for both quality control of hiPSC-derived hepatocytes and hepatotoxicity screening.
Publisher	American Chemical Society
Source Title	Analytical Chemistry
Volume (Issue)	95(24)
Page	9252-9262
Date of Issued	2023-06-09
Language	English
Handle URL	https://hdl.handle.net/11094/103302
PISSN	00032700
eISSN	15206882
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1021/acs.analchem.3c00976
Access Rights	open access
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Analytical Chemistry. 2023, 95(24), p. 9252-9262
DC.title	Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging
DC.creator	Li, Menglu
	Ueyama-Toba, Yukiko
	Lindley, Matthew
	Kongklad, Gunganist
	Nawa, Yasunori
	Kumamoto, Yasuaki
	Ishida, Seiichi
	Kanda, Yasunari
	Fujita, Satoshi
	Mizuguchi, Hiroyuki
	Fujita, Katsumasa
DC.publisher	American Chemical Society
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-06-09
DC.identifier	https://doi.org/10.1021/acs.analchem.3c00976
DC.description	This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry 95, 9252 (2023), © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.analchem.3c00976.
DCTERMS.abstract	To promote the clinical application of human induced pluripotent stem cell (hiPSC)-derived hepatocytes, a method capable of monitoring regenerative processes and assessing differentiation efficiency without harming or modifying these cells is important. Raman microscopy provides a powerful tool for this as it enables label-free identification of intracellular biomolecules in live samples. Here, we used label-free Raman microscopy to assess hiPSC differentiation into hepatocyte lineage based on the intracellular chemical content. We contrasted these data with similar phenotypes from the HepaRG and from commercially available hiPSC-derived hepatocytes (iCell hepatocytes). We detected hepatic cytochromes, lipids, and glycogen in hiPSC-derived hepatocyte-like cells (HLCs) but not biliary-like cells (BLCs), indicating intrinsic differences in biomolecular content between these phenotypes. The data show significant glycogen and lipid accumulation as early as the definitive endoderm transition. Additionally, we explored the use of Raman imaging as a hepatotoxicity assay for the HepaRG and iCell hepatocytes, with data displaying a dose-dependent reduction of glycogen accumulation in response to acetaminophen. These findings show that the nondestructive and high-content nature of Raman imaging provides a promising tool for both quality control of hiPSC-derived hepatocytes and hepatotoxicity screening.
DC.format	103302
citation_title	Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging
citation_author	Li, Menglu
	Ueyama-Toba, Yukiko
	Lindley, Matthew
	Kongklad, Gunganist
	Nawa, Yasunori
	Kumamoto, Yasuaki
	Ishida, Seiichi
	Kanda, Yasunari
	Fujita, Satoshi
	Mizuguchi, Hiroyuki
	Fujita, Katsumasa
citation_publisher	American Chemical Society
citation_language	English
citation_date	2023-06-09
citation_journal_title	Analytical Chemistry
citation_volume	95
citation_issue	24
citation_firstpage	9252
citation_lastpage	9262
citation_doi	https://doi.org/10.1021/acs.analchem.3c00976
citation_public_url	https://hdl.handle.net/11094/103302

Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging

Link to primary information

Item Information

Show details