title: Macromolecular crowding meets oxygen tension in human mesenchymal stem cell culture - A step closer to physiologically relevant in vitro organogenesis.
abstract: Modular tissue engineering is based on the cells' innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes.
authors.affiliation: Regenerative, Modular &Developmental Engineering Laboratory (REMODEL), Biosciences Research Building, National University of Ireland Galway (NUI Galway), Galway, Ireland.|Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cigognini
authors.affiliation: Regenerative, Modular &Developmental Engineering Laboratory (REMODEL), Biosciences Research Building, National University of Ireland Galway (NUI Galway), Galway, Ireland.|Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Diana
authors.initials: D
authors.lastname: Gaspar
authors.affiliation: Regenerative, Modular &Developmental Engineering Laboratory (REMODEL), Biosciences Research Building, National University of Ireland Galway (NUI Galway), Galway, Ireland.|Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Regenerative, Modular &Developmental Engineering Laboratory (REMODEL), Biosciences Research Building, National University of Ireland Galway (NUI Galway), Galway, Ireland.|Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Abhigyan
authors.initials: A
authors.lastname: Satyam
authors.affiliation: Regenerative Medicine Institute (REMEDI), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Alagesan
authors.affiliation: Regenerative Medicine Institute (REMEDI), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Clara
authors.initials: C
authors.lastname: Sanz-Nogués
authors.affiliation: Regenerative Medicine Institute (REMEDI), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Griffin
authors.affiliation: Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, NUI Galway, Galway, Ireland.|Regenerative Medicine Institute (REMEDI), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
authors.affiliation: Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
authors.affiliation: Regenerative, Modular &Developmental Engineering Laboratory (REMODEL), Biosciences Research Building, National University of Ireland Galway (NUI Galway), Galway, Ireland.|Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, NUI Galway, Galway, Ireland.
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Zeugolis
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D038081:Organogenesis; D010100:Oxygen / Q000378:metabolism*; D023822:Tissue Engineering
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen