Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy.
Suitable cell models are essential to advance our understanding of the pathogenesis of liver diseases and the development of therapeutic strategies. Primary human hepatocytes (PHHs), the most ideal hepatic model, are commercially available, but they are expensive and vary from lot-to-lot which confo...
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ftdoajarticles:oai:doaj.org/article:d2244e73e3144e56b99c0067fffb6c35 2023-05-15T15:13:25+02:00 Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. Kessiri Kongmanas Nuntaya Punyadee Kasima Wasuworawong Adisak Songjaeng Tanapan Prommool Yongyut Pewkliang Siriphan Manocheewa Somchai Thiemmeca Khanit Sa-Ngiamsuntorn Chunya Puttikhunt Kym Francis Faull Suradej Hongeng Panisadee Avirutnan 2020-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008835 https://doaj.org/article/d2244e73e3144e56b99c0067fffb6c35 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008835 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008835 https://doaj.org/article/d2244e73e3144e56b99c0067fffb6c35 PLoS Neglected Tropical Diseases, Vol 14, Iss 11, p e0008835 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008835 2022-12-31T12:51:32Z Suitable cell models are essential to advance our understanding of the pathogenesis of liver diseases and the development of therapeutic strategies. Primary human hepatocytes (PHHs), the most ideal hepatic model, are commercially available, but they are expensive and vary from lot-to-lot which confounds their utility. We have recently developed an immortalized hepatocyte-like cell line (imHC) from human mesenchymal stem cells, and tested it for use as a substitute model for hepatotropic infectious diseases. With a special interest in liver pathogenesis of viral infection, herein we determined the suitability of imHC as a host cell target for dengue virus (DENV) and as a model for anti-viral drug testing. We characterized the kinetics of DENV production, cellular responses to DENV infection (apoptosis, cytokine production and lipid droplet metabolism), and examined anti-viral drug effects in imHC cells with comparisons to the commonly used hepatoma cell lines (HepG2 and Huh-7) and PHHs. Our results showed that imHC cells had higher efficiencies in DENV replication and NS1 secretion as compared to HepG2 and Huh-7 cells. The kinetics of DENV infection in imHC cells showed a slower rate of apoptosis than the hepatoma cell lines and a certain similarity of cytokine profiles to PHHs. In imHC, DENV-induced alterations in levels of lipid droplets and triacylglycerols, a major component of lipid droplets, were more apparent than in hepatoma cell lines, suggesting active lipid metabolism in imHC. Significantly, responses to drugs with DENV inhibitory effects were greater in imHC cells than in HepG2 and Huh-7 cells. In conclusion, our findings suggest superior suitability of imHC as a new hepatocyte model for studying mechanisms underlying viral pathogenesis, liver diseases and drug effects. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 11 e0008835 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Kessiri Kongmanas Nuntaya Punyadee Kasima Wasuworawong Adisak Songjaeng Tanapan Prommool Yongyut Pewkliang Siriphan Manocheewa Somchai Thiemmeca Khanit Sa-Ngiamsuntorn Chunya Puttikhunt Kym Francis Faull Suradej Hongeng Panisadee Avirutnan Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Suitable cell models are essential to advance our understanding of the pathogenesis of liver diseases and the development of therapeutic strategies. Primary human hepatocytes (PHHs), the most ideal hepatic model, are commercially available, but they are expensive and vary from lot-to-lot which confounds their utility. We have recently developed an immortalized hepatocyte-like cell line (imHC) from human mesenchymal stem cells, and tested it for use as a substitute model for hepatotropic infectious diseases. With a special interest in liver pathogenesis of viral infection, herein we determined the suitability of imHC as a host cell target for dengue virus (DENV) and as a model for anti-viral drug testing. We characterized the kinetics of DENV production, cellular responses to DENV infection (apoptosis, cytokine production and lipid droplet metabolism), and examined anti-viral drug effects in imHC cells with comparisons to the commonly used hepatoma cell lines (HepG2 and Huh-7) and PHHs. Our results showed that imHC cells had higher efficiencies in DENV replication and NS1 secretion as compared to HepG2 and Huh-7 cells. The kinetics of DENV infection in imHC cells showed a slower rate of apoptosis than the hepatoma cell lines and a certain similarity of cytokine profiles to PHHs. In imHC, DENV-induced alterations in levels of lipid droplets and triacylglycerols, a major component of lipid droplets, were more apparent than in hepatoma cell lines, suggesting active lipid metabolism in imHC. Significantly, responses to drugs with DENV inhibitory effects were greater in imHC cells than in HepG2 and Huh-7 cells. In conclusion, our findings suggest superior suitability of imHC as a new hepatocyte model for studying mechanisms underlying viral pathogenesis, liver diseases and drug effects. |
format |
Article in Journal/Newspaper |
author |
Kessiri Kongmanas Nuntaya Punyadee Kasima Wasuworawong Adisak Songjaeng Tanapan Prommool Yongyut Pewkliang Siriphan Manocheewa Somchai Thiemmeca Khanit Sa-Ngiamsuntorn Chunya Puttikhunt Kym Francis Faull Suradej Hongeng Panisadee Avirutnan |
author_facet |
Kessiri Kongmanas Nuntaya Punyadee Kasima Wasuworawong Adisak Songjaeng Tanapan Prommool Yongyut Pewkliang Siriphan Manocheewa Somchai Thiemmeca Khanit Sa-Ngiamsuntorn Chunya Puttikhunt Kym Francis Faull Suradej Hongeng Panisadee Avirutnan |
author_sort |
Kessiri Kongmanas |
title |
Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. |
title_short |
Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. |
title_full |
Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. |
title_fullStr |
Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. |
title_full_unstemmed |
Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. |
title_sort |
immortalized stem cell-derived hepatocyte-like cells: an alternative model for studying dengue pathogenesis and therapy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008835 https://doaj.org/article/d2244e73e3144e56b99c0067fffb6c35 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 11, p e0008835 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008835 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008835 https://doaj.org/article/d2244e73e3144e56b99c0067fffb6c35 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008835 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
11 |
container_start_page |
e0008835 |
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1766343969268039680 |