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Characterization of...
Characterization of Human Induced Pluripotent Stem Cell-Derived Hepatocytes with Mature Features and Potential for Modeling Metabolic Diseases
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- Holmgren, Gustav, 1983- (author)
- Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Translationell bioinformatik, Translational Bioinformatics
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- Ulfenborg, Benjamin, 1985- (author)
- Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Translationell bioinformatik, Translational Bioinformatics
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- Asplund, A. (author)
- R&D, Hepatocyte Product Development, Takara Bio Europe AB, Gothenburg, Sweden
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- Toet, K. (author)
- Department of Metabolic Health Research, TNO, Leiden, The Netherlands
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- Andersson, C. X. (author)
- R&D, Hepatocyte Product Development, Takara Bio Europe AB, Gothenburg, Sweden
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- Hammarstedt, Ann, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,The Lundberg Laboratory for Diabetes Research, Departments of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Kuppers-Munther, B. (author)
- R&D, Hepatocyte Product Development, Takara Bio Europe AB, Gothenburg, Sweden
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- Synnergren, Jane (author)
- Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Translationell bioinformatik, Translational Bioinformatics
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- Hanemaaijer, Roeland (author)
- Department of Metabolic Health Research, TNO, Leiden, The Netherlands
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(creator_code:org_t)
- 2020-01-11
- 2020
- English.
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:2
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Abstract
Subject headings
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- There is a strong anticipated future for human induced pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far, their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g., Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, low-density lipoproteins (LDL), and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker tumor necrosis factor alpha (TNF alpha) was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling non-alcoholic steatohepatitis (NASH). Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- human induced pluripotent stem cells
- human stem cell-derived
- hepatocytes
- in vitro
- metabolic diseases
- transcriptomics
- maturation
- characterization
- fatty liver-disease
- density-lipoprotein receptor
- in-vitro
- nonalcoholic steatohepatitis
- cytochromes p450
- differentiation
- quantification
- hnf4-alpha
- activation
- expression
- Biochemistry & Molecular Biology
- Chemistry
- characterization
- Bioinformatik
Publication and Content Type
- ref (subject category)
- art (subject category)
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