Laminin-511 and laminin-521-based matrices for efficient hepatic specification of human pluripotent stem cells. (October 2016)

• Record Type: Journal Article
• Authors: Kanninen, Liisa K.; Harjumäki, Riina; Peltoniemi, Pasi; Bogacheva, Mariia S.; Salmi, Tuuli; Porola, Pauliina; Niklander, Johanna; Smutný, Tomáš; Urtti, Arto; Yliperttula, Marjo L.; Lou, Yan-Ru
• Is Part Of: Biomaterials. Volume 103(2016)
• Page Start: 86
• Page End: 100
• Publication Date: 2016-10
• Subjects: Extracellular matrix -- Human embryonic stem cell -- Human induced pluripotent stem cell -- Hepatic differentiation -- Laminin-511 -- Laminin-521; ACM acellular matrix -- Act A Activin A -- AAT alpha-1 antitrypsin -- AFP alpha fetoprotein -- ALB albumin -- AhR aryl hydrocarbon receptor -- BMP bone morphogenetic protein -- CK cytokeratin -- CXCR-4 chemokine receptor type 4 -- CYP cytochrome P450 -- DE definite endoderm -- DEX dexamethasone -- ECM extracellular matrix -- F-actin filamentous actin -- FBS fetal bovine serum -- FGF fibroblast growth factor -- HCM hepatocyte culture medium -- hESC human embryonic stem cell -- HGF hepatocyte growth factor -- HNF hepatocyte nuclear factor -- hPSC human pluripotent stem cell -- hiPSC human induced pluripotent stem cell -- LN laminin -- NR1I2 nuclear receptor subfamily 1, group I, member 2 -- NR3C1 nuclear receptor subfamily 3, group C, member 1 -- OCT4 octamer-binding transcription factor 4 -- OMZ omeprazole -- OSM oncostatin M -- PHH primary human hepatocyte -- qPCR quantitative polymerase chain reaction -- rhEGF recombinant human epidermal growth factor -- SSEA stage-specific embryonic antigen -- Wnt wingless type; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2016.06.054
• Languages: English
• ISSNs: 0142-9612

Abstract

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.