Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

Autor: Anders Aspegren, Viktoriia Starokozhko, Anders Wolff, Soumyaranjan Mohanty, Marjolijn T. Merema, Layla Bashir Larsen, Jenny Emnéus, Rodrigo Pimentel, Mette Hemmingsen, Martin Dufva, Geny M. M. Groothuis
Přispěvatelé: Nanomedicine & Drug Targeting
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Medicine (miscellaneous)
Stem cells
law.invention
0302 clinical medicine
law
Gene expression
PERFUSION
Urea
CULTURE-SYSTEM
Induced pluripotent stem cell
Research Articles
Cells
Cultured
Bioartificial liver
Tissue Scaffolds
Chemistry
HUMAN FETAL LIVER
Hepatic differentiation
Cell Differentiation
Cell biology
Liver
bioartificial liver
030220 oncology & carcinogenesis
Toxicity
Stem cell
Rheology
Research Article
HEPATIC DIFFERENTIATION
Induced Pluripotent Stem Cells
Biomedical Engineering
Isozyme
TRANSDUCTION
Bile Acids and Salts
Biomaterials
03 medical and health sciences
In vivo
stem cells
Albumins
Humans
BIOARTIFICIAL LIVERS
MICROFLUIDICS
Tissue Engineering
Bioartificial liver device
030104 developmental biology
Gene Expression Regulation
DRUG-METABOLISM
Hepatocytes
EFFICIENT GENERATION
Biomarkers
Drug metabolism
BIOREACTOR
Zdroj: Journal of Tissue Engineering and Regenerative Medicine
Journal of tissue engineering and regenerative medicine, 12(5), 1273-1284. Wiley
Starokozhko, V, Hemmingsen, M, Larsen, L, Mohanty, S, Merema, M, Pimentel, R C, Wolff, A, Emnéus, J, Aspegren, A, Groothuis, G & Dufva, M 2018, ' Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering ', Journal of Tissue Engineering and Regenerative Medicine, vol. 12, no. 5, pp. 1273-1284 . https://doi.org/10.1002/term.2659
ISSN: 1932-6254
DOI: 10.1002/term.2659
Popis: Hepatic differentiation of human‐induced pluripotent stem cells (hiPSCs) under flow conditions in a 3D scaffold is expected to be a major step forward for construction of bioartificial livers. The aims of this study were to induce hepatic differentiation of hiPSCs under perfusion conditions and to perform functional comparisons with fresh human precision‐cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis in the hiPSC‐derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted in slightly lower activity of some of the Phase I metabolism enzymes. Gene expression data indicate that hiPSCs differentiated into both hepatic and biliary directions. In conclusion, the hiPSC differentiated under flow conditions towards hepatocytes express a wide spectrum of liver functions at levels comparable with hPCLS indicating excellent future perspectives for the development of a bioartificial liver system for toxicity testing or as liver support device for patients.
Databáze: OpenAIRE
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