title: Substrate-mediated commitment of human embryonic stem cells for hepatic differentiation.
abstract: Human embryonic stem cell (hESC)-derived endodermal cells are of interest for the development of cellular therapies to treat disorders such as liver failure. The soluble form of activin A (Act) has been widely used as an in vitro inducer of definitive endoderm (DE). In this study, we have developed a nanofibrous poly (ɛ-caprolactone) substrate, biofunctionalized with Act, for directed differentiation of hESCs into DE. Bioconjugation of Act on nanofibrous meshes was confirmed by enzyme-linked immunosorbent assay (ELISA) and immunostaining. In order to investigate the bioactivity of immobilized Act (iAct), hESCs were cultivated on the Act-conjugated nanofibers for five days. The nanofibers with covalent iAct significantly increased expression levels of the endodermal markers SOX17, FOXA2, and CXCR4, compared with physically adsorbed Act (aAct) or without Act (noAct). In addition, iAct retained its bioactivity after storage for five days in the absence of cell seeding. The capability of cultivated cells to generate the DE-derived lineage was evaluated through further differentiation of seeded cells into hepatocyte-like cells (HLCs). Interestingly, the iAct sample showed a higher level of hepatic markers compared to the aAct sample. We also demonstrated that iAct in the presence of soluble Act (sAct) could improve the conventional protocol to generate HLCs from hESCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2861-2872, 2016.
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.|Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran, Iran.
authors.forename: Mohammad Kazemi
authors.initials: MK
authors.lastname: Ashtiani
authors.affiliation: Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran, Iran. Baharvand@RoyanInstitute.org.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Zandi
authors.affiliation: Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran, Iran.
authors.forename: Jalal
authors.initials: J
authors.lastname: Barzin
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Tahamtani
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.|Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghanian
authors.affiliation: Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Moradmand
authors.affiliation: Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Ehsani
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nezari
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Mehran Rezaei
authors.initials: MR
authors.lastname: Larijani
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. M.Zandi@ippi.ac.ir.|Department of Developmental Biology, University of Science and Culture, Tehran, Iran. M.Zandi@ippi.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D028341:Activins / Q000737:chemistry / Q000378:metabolism*; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D001672:Biocompatible Materials; D055767:Immobilized Proteins; C422405:activin A; D028341:Activins
keywords: activin A; electrospun nanofibers; embryonic stem cells; growth factor immobilization; hepatocyte-like cells