title: Defined and Scalable Generation of Hepatocyte-like Cells from Human Pluripotent Stem Cells.
abstract: Human pluripotent stem cells (hPSCs) possess great value for biomedical research. hPSCs can be scaled and differentiated to all cell types found in the human body. The differentiation of hPSCs to human hepatocyte-like cells (HLCs) has been extensively studied, and efficient differentiation protocols have been established. The combination of extracellular matrix and biological stimuli, including growth factors, cytokines, and small molecules, have made it possible to generate HLCs that resemble primary human hepatocytes. However, the majority of procedures still employ undefined components, giving rise to batch-to-batch variation. This serves as a significant barrier to the application of the technology. To tackle this issue, we developed a defined system for hepatocyte differentiation using human recombinant laminins as extracellular matrices in combination with a serum-free differentiation process. Highly efficient hepatocyte specification was achieved, with demonstrated improvements in both HLC function and phenotype. Importantly, this system is easy to scale up using research and GMP-grade hPSC lines promising advances in cell-based modelling and therapies.
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh.
authors.forename: Sharmin
authors.initials: S
authors.lastname: Alhaque
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh.
authors.forename: Kate
authors.initials: K
authors.lastname: Cameron
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh.
authors.forename: Jose
authors.initials: J
authors.lastname: Meseguer-Ripolles
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh.
authors.forename: Baltasar
authors.initials: B
authors.lastname: Lucendo-Villarin
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rashidi
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh; davehay@talktalk.net.
authors.forename: David C
authors.initials: DC
authors.lastname: Hay
mesh_terms: D002452:Cell Count; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology*