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Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes

Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into proge...

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Autores principales: Katsuda, Takeshi, Matsuzaki, Juntaro, Yamaguchi, Tomoko, Yamada, Yasuhiro, Prieto-Vila, Marta, Hosaka, Kazunori, Takeuchi, Atsuko, Saito, Yoshimasa, Ochiya, Takahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731094/
https://www.ncbi.nlm.nih.gov/pubmed/31393263
http://dx.doi.org/10.7554/eLife.47313
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author Katsuda, Takeshi
Matsuzaki, Juntaro
Yamaguchi, Tomoko
Yamada, Yasuhiro
Prieto-Vila, Marta
Hosaka, Kazunori
Takeuchi, Atsuko
Saito, Yoshimasa
Ochiya, Takahiro
author_facet Katsuda, Takeshi
Matsuzaki, Juntaro
Yamaguchi, Tomoko
Yamada, Yasuhiro
Prieto-Vila, Marta
Hosaka, Kazunori
Takeuchi, Atsuko
Saito, Yoshimasa
Ochiya, Takahiro
author_sort Katsuda, Takeshi
collection PubMed
description Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies.
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spelling pubmed-67310942019-09-10 Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes Katsuda, Takeshi Matsuzaki, Juntaro Yamaguchi, Tomoko Yamada, Yasuhiro Prieto-Vila, Marta Hosaka, Kazunori Takeuchi, Atsuko Saito, Yoshimasa Ochiya, Takahiro eLife Cell Biology Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies. eLife Sciences Publications, Ltd 2019-08-08 /pmc/articles/PMC6731094/ /pubmed/31393263 http://dx.doi.org/10.7554/eLife.47313 Text en © 2019, Katsuda et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Katsuda, Takeshi
Matsuzaki, Juntaro
Yamaguchi, Tomoko
Yamada, Yasuhiro
Prieto-Vila, Marta
Hosaka, Kazunori
Takeuchi, Atsuko
Saito, Yoshimasa
Ochiya, Takahiro
Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
title Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
title_full Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
title_fullStr Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
title_full_unstemmed Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
title_short Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
title_sort generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731094/
https://www.ncbi.nlm.nih.gov/pubmed/31393263
http://dx.doi.org/10.7554/eLife.47313
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