title: Analysis of oxygen-dependent cytokine expression in human mesenchymal stem cells derived from umbilical cord.
abstract: Efficient cell expansion is a basic requirement for obtaining clinically relevant numbers of mesenchymal stem cells designed for cell-based therapies or tissue-engineering application. Previous studies have demonstrated that mesenchymal stem cells (MSC) cultivated under reduced atmospheric oxygen concentrations (2.5% O2) possess enhanced proliferation potential and can maintain their differentiation properties. We have analyzed the oxygen-dependent cytokine expression of human MSC derived from umbilical cord and attempted to link the results to the proliferation and differentiation capacities of these cells. By quantitative reverse transcription plus the polymerase chain reaction and by protein microarray, we measured the gene expression and intracellular protein concentration of several growth factors and growth factor receptors. Fibroblast growth factor-7, two growth factor receptors (vascular endothelial growth factor receptor 2 and stem cell factor receptor), and two growth-factor-binding proteins (insulin-like growth-factor-binding proteins 3 and 6) were over-expressed under hypoxic conditions, indicating that their signaling pathways participate in cell proliferation. On the other hand, typical differentiation factors such as bone morphogenetic protein-4, endothelial growth factor, and tissue growth factor-β1 were absent in cells cultivated under hypoxic and normoxic conditions. The absolute concentration of some intracellular cytokines was also measured for the first time under hypoxia and normoxia. Our results in combination with previous findings indicate that enhanced proliferation potential and a maintained undifferentiated cell state can be ascribed to the oxygen-dependent expression of a set of cytokines. This knowledge might help in the understanding of MSC physiology and in the achievement of directed cell fate of MSC for clinical application.
authors.affiliation: Institute of Technical Chemistry, Leibniz University Hanover, Callinstrasse 5, 30167, Hannover, Germany. loenne@iftc.uni-hannover.de
authors.forename: Maren
authors.initials: M
authors.lastname: Lönne
authors.forename: Antonina
authors.initials: A
authors.lastname: Lavrentieva
authors.forename: Johanna-Gabriela
authors.initials: JG
authors.lastname: Walter
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kasper
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000172:deficiency; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000172:deficiency; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000096:biosynthesis / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D016228:Endothelial Growth Factors; C496453:FGF7 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018976:Insulin-Like Growth Factor Binding Protein 6; D053773:Transforming Growth Factor beta1; D051523:Fibroblast Growth Factor 7; D019009:Proto-Oncogene Proteins c-kit; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen