hiPSC‐derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver

Autor: Dimple Kauhanen, Leena E. Viiri, Kim Ekroos, Mostafa Kiamehr, Laura Heiskanen, Reijo Käkelä, Anna Alexanova, Reijo Laaksonen, Terhi Vihervaara, Katriina Aalto-Setälä
Přispěvatelé: Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, Tampere University, Physiology and Neuroscience (-2020), Functional Lipidomics Group, Molecular and Integrative Biosciences Research Programme
Rok vydání: 2018
Předmět:
0301 basic medicine
human-induced pluripotent stem cell (hiPSC)
Physiology
gas chromatography
Clinical Biochemistry
fatty acid (FA)
Mass Spectrometry
FATTY-ACID SYNTHASE
0302 clinical medicine
HUMAN PLASMA
Induced pluripotent stem cell
GENE-EXPRESSION
medicine.diagnostic_test
Chemistry
Fatty Acids
STEAROYL-COA DESATURASE
Cell Differentiation
Hep G2 Cells
Cell biology
Phenotype
DIFFERENTIATION
medicine.anatomical_structure
030220 oncology & carcinogenesis
Hepatocyte
hepatocyte-like cell (HLC)
Life Sciences & Biomedicine
PLURIPOTENT STEM-CELLS
HepG2
Chromatography
Gas
Biolääketieteet - Biomedicine
education
Induced Pluripotent Stem Cells
Primary Cell Culture
primary human hepatocyte (PHH)
MECHANISMS
Biokemia
solu- ja molekyylibiologia - Biochemistry
cell and molecular biology
03 medical and health sciences
CERAMIDE SYNTHASES
Lipidomics
medicine
Humans
mass spectrometry (MS)
Cell Shape
Science & Technology
Lipid metabolism
Cell Biology
Metabolism
Lipid Metabolism
HEPATIC ENDODERM
030104 developmental biology
Gene Expression Regulation
Cell culture
Hepatocytes
1182 Biochemistry
cell and molecular biology
lipidomics
Lysophospholipids
Lipid profile
GENERATION
Lipoprotein
Zdroj: Journal of Cellular Physiology. 234:3744-3761
ISSN: 1097-4652
0021-9541
DOI: 10.1002/jcp.27131
Popis: Hepatocyte-like cells (HLCs) differentiated from human-induced pluripotent stem cells offer an alternative platform to primary human hepatocytes (PHHs) for studying the lipid metabolism of the liver. However, despite their great potential, the lipid profile of HLCs has not yet been characterized. Here, we comprehensively studied the lipid profile and fatty acid (FA) metabolism of HLCs and compared them with the current standard hepatocyte models: HepG2 cells and PHHs. We differentiated HLCs by five commonly used methods from three cell lines and thoroughly characterized them by gene and protein expression. HLCs generated by each method were assessed for their functionality and the ability to synthesize, elongate, and desaturate FAs. In addition, lipid and FA profiles of HLCs were investigated by both mass spectrometry and gas chromatography and then compared with the profiles of PHHs and HepG2 cells. HLCs resembled PHHs by expressing hepatic markers: secreting albumin, lipoprotein particles, and urea, and demonstrating similarities in their lipid and FA profile. Unlike HepG2 cells, HLCs contained low levels of lysophospholipids similar to the content of PHHs. Furthermore, HLCs were able to efficiently use the exogenous FAs available in their medium and simultaneously modify simple lipids into more complex ones to fulfill their needs. In addition, we propose that increasing the polyunsaturated FA supply of the culture medium may positively affect the lipid profile and functionality of HLCs. In conclusion, our data showed that HLCs provide a functional and relevant model to investigate human lipid homeostasis at both molecular and cellular levels. ispartof: JOURNAL OF CELLULAR PHYSIOLOGY vol:234 issue:4 pages:3744-3761 ispartof: location:United States status: published
Databáze: OpenAIRE
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