Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH
Non-alcoholic steatohepatitis (NASH) is a severe chronic liver disease that affects 3 to 5 percent of the world population. It is characterized by hepatic lipid accumulation and inflammation and can progress towards fibrosis, cirrhosis and hepatocellular carcinoma. Until today, no drug has been appr...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | MethodsX |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2215016120302880 |
| _version_ | 1819057126763397120 |
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| author | Joost Boeckmans Alessandra Natale Matthias Rombaut Karolien Buyl Tamara Vanhaecke Vera Rogiers Robim M Rodrigues Joery De Kock |
| author_facet | Joost Boeckmans Alessandra Natale Matthias Rombaut Karolien Buyl Tamara Vanhaecke Vera Rogiers Robim M Rodrigues Joery De Kock |
| author_sort | Joost Boeckmans |
| collection | DOAJ |
| description | Non-alcoholic steatohepatitis (NASH) is a severe chronic liver disease that affects 3 to 5 percent of the world population. It is characterized by hepatic lipid accumulation and inflammation and can progress towards fibrosis, cirrhosis and hepatocellular carcinoma. Until today, no drug has been approved for the treatment of NASH. This delay relates to the complex pathogenesis of NASH and also to a lack of appropriate predictive preclinical testing systems. Furthermore, the human specificity of the NASH pathology hampers a fortiori clinical translation of animal studies.Therefore, we recently employed human skin-derived precursors (hSKP) differentiated to hepatocyte-like cells (hSKP-HPC) as a human-relevant cell source for modelling NASH in vitro. Using this in vitro NASH model, it was possible to test novel drugs being developed for anti-NASH therapy, such as elafibranor. Since steatosis is an important aspect of NASH and multiple drugs are being developed to decelerate and reduce lipid accumulation in the liver, we optimized a flow cytometric method for quantifying neutral lipids in ‘NASH’-triggered hSKP-HPC. This methodology enables efficient identification of anti-steatotic properties of new medicines.• NASH-triggered hSKP-HPC robustly accumulate lipids intracellularly.• Flow cytometric quantification of neutral lipids in NASH-triggered hSKP-HPC allows for accurate determination of the steatotic response.• This method enables efficient identification of potential anti-steatotic drugs in a human-specific model |
| first_indexed | 2024-12-21T13:34:21Z |
| format | Article |
| id | doaj.art-a3aff3daa9b64c03bede64425e26eb5e |
| institution | Directory Open Access Journal |
| issn | 2215-0161 |
| language | English |
| last_indexed | 2024-12-21T13:34:21Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | MethodsX |
| spelling | doaj.art-a3aff3daa9b64c03bede64425e26eb5e2022-12-21T19:02:12ZengElsevierMethodsX2215-01612020-01-017101068Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASHJoost Boeckmans0Alessandra Natale1Matthias Rombaut2Karolien Buyl3Tamara Vanhaecke4Vera Rogiers5Robim M Rodrigues6Joery De Kock7Corresponding author.; Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumDepartment of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, BelgiumNon-alcoholic steatohepatitis (NASH) is a severe chronic liver disease that affects 3 to 5 percent of the world population. It is characterized by hepatic lipid accumulation and inflammation and can progress towards fibrosis, cirrhosis and hepatocellular carcinoma. Until today, no drug has been approved for the treatment of NASH. This delay relates to the complex pathogenesis of NASH and also to a lack of appropriate predictive preclinical testing systems. Furthermore, the human specificity of the NASH pathology hampers a fortiori clinical translation of animal studies.Therefore, we recently employed human skin-derived precursors (hSKP) differentiated to hepatocyte-like cells (hSKP-HPC) as a human-relevant cell source for modelling NASH in vitro. Using this in vitro NASH model, it was possible to test novel drugs being developed for anti-NASH therapy, such as elafibranor. Since steatosis is an important aspect of NASH and multiple drugs are being developed to decelerate and reduce lipid accumulation in the liver, we optimized a flow cytometric method for quantifying neutral lipids in ‘NASH’-triggered hSKP-HPC. This methodology enables efficient identification of anti-steatotic properties of new medicines.• NASH-triggered hSKP-HPC robustly accumulate lipids intracellularly.• Flow cytometric quantification of neutral lipids in NASH-triggered hSKP-HPC allows for accurate determination of the steatotic response.• This method enables efficient identification of potential anti-steatotic drugs in a human-specific modelhttp://www.sciencedirect.com/science/article/pii/S2215016120302880Flow cytometric quantification of neutral lipids in human skin-derived hepatic cells |
| spellingShingle | Joost Boeckmans Alessandra Natale Matthias Rombaut Karolien Buyl Tamara Vanhaecke Vera Rogiers Robim M Rodrigues Joery De Kock Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH MethodsX Flow cytometric quantification of neutral lipids in human skin-derived hepatic cells |
| title | Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH |
| title_full | Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH |
| title_fullStr | Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH |
| title_full_unstemmed | Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH |
| title_short | Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH |
| title_sort | flow cytometric quantification of neutral lipids in a human skin stem cell derived model of nash |
| topic | Flow cytometric quantification of neutral lipids in human skin-derived hepatic cells |
| url | http://www.sciencedirect.com/science/article/pii/S2215016120302880 |
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