title: Oxygenated environment enhances both stem cell survival and osteogenic differentiation.
abstract: Osteogenesis of mesenchymal stem cells (MSCs) is highly dependent on oxygen supply. We have shown that perfluorotributylamine (PFTBA), a synthetic oxygen carrier, enhances MSC-based bone formation in vivo. Exploring this phenomenon's mechanism, we hypothesize that a transient increase in oxygen levels using PFTBA will affect MSC survival, proliferation, and differentiation, thus increasing bone formation. To test this hypothesis, MSCs overexpressing bone morphogenetic protein 2 were encapsulated in alginate beads that had been supplemented with an emulsion of PFTBA or phosphate-buffered saline. Oxygen measurements showed that supplementation of PFTBA significantly increased the available oxygen level during a 96-h period. PFTBA-containing beads displayed an elevation in cell viability, which was preserved throughout 2 weeks, and a significantly lower ratio of dead cells throughout the experiment. Furthermore, the cells from the control group expressed significantly more hypoxia-related genes such as VEGF, DDIT3, and PKG1. Additionally, PFTBA supplementation led to an increase in the osteogenic differentiation and to a decrease in chondrogenic differentiation of MSCs. In conclusion, PFTBA increases the oxygen availability in the vicinity of the MSCs, which suffer oxygen exhaustion shortly after encapsulation in alginate beads. Consequently, cell survival is increased, and hypoxia-related genes are downregulated. In addition, PFTBA promotes osteogenic differentiation over chondrogeneic differentiation, and thereby can accelerate MSC-based bone regeneration.
authors.affiliation: Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Shimon
authors.initials: S
authors.lastname: Benjamin
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Sheyn
authors.forename: Shiran
authors.initials: S
authors.lastname: Ben-David
authors.forename: Anthony
authors.initials: A
authors.lastname: Oh
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D040521:Subcutaneous Tissue / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D005466:Fluorocarbons; C008807:perfluorotributylamine; D010100:Oxygen