Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783449631145852928 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6731094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT katsudatakeshi generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT matsuzakijuntaro generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT yamaguchitomoko generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT yamadayasuhiro generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT prietovilamarta generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT hosakakazunori generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT takeuchiatsuko generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT saitoyoshimasa generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes AT ochiyatakahiro generationofhumanhepaticprogenitorcellswithregenerativeandmetaboliccapacitiesfromprimaryhepatocytes |