title: Laminin-511 and laminin-521-based matrices for efficient hepatic specification of human pluripotent stem cells.
abstract: Human pluripotent stem cells (hPSCs) have gained a solid foothold in basic research and drug industry as they can be used in vitro to study human development and have potential to offer limitless supply of various somatic cell types needed in drug development. Although the hepatic differentiation of hPSCs has been extensively studied, only a little attention has been paid to the role of the extracellular matrix. In this study we used laminin-511, laminin-521, and fibronectin, found in human liver progenitor cells, as culture matrices for hPSC-derived definitive endoderm cells. We observed that laminin-511 and laminin-521 either alone or in combination support the hepatic specification and that fibronectin is not a vital matrix protein for the hPSC-derived definitive endoderm cells. The expression of the laminin-511/521-specific integrins increased during the definitive endoderm induction and hepatic specification. The hepatic cells differentiated on laminin matrices showed the upregulation of liver-specific markers both at mRNA and protein levels, secreted human albumin, stored glycogen, and exhibited cytochrome P450 enzyme activity and inducibility. Altogether, we found that laminin-511 and laminin-521 can be used as stage-specific matrices to guide the hepatic specification of hPSC-derived definitive endoderm cells.
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Liisa K
authors.initials: LK
authors.lastname: Kanninen
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Riina
authors.initials: R
authors.lastname: Harjumäki
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Peltoniemi
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Mariia S
authors.initials: MS
authors.lastname: Bogacheva
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Salmi
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Pauliina
authors.initials: P
authors.lastname: Porola
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Niklander
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, 50005 Hradec Králové, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Smutný
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland; School of Pharmacy, University of Eastern Finland, P. O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland.
authors.forename: Marjo L
authors.initials: ML
authors.lastname: Yliperttula
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, FI-00014 Helsinki, Finland. Electronic address: yan-ru.lou@helsinki.fi.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Lou
mesh_terms: D061249:Batch Cell Culture Techniques / Q000379:methods; D040761:Biomimetic Materials / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods
chemical_list: D016326:Extracellular Matrix Proteins; D007797:Laminin
keywords: Extracellular matrix; Hepatic differentiation; Human embryonic stem cell; Human induced pluripotent stem cell; Laminin-511; Laminin-521