title: TGF-beta1 does not induce senescence of multipotent mesenchymal stromal cells and has similar effects in early and late passages.
abstract: Transforming growth factor-beta 1 (TGF-β1) stimulates a broad range of effects which are cell type dependent, and it has been suggested to induce cellular senescence. On the other hand, long-term culture of multipotent mesenchymal stromal cells (MSCs) has a major impact on their cellular physiology and therefore it is well conceivable that the molecular events triggered by TGF-β1 differ considerably in cells of early and late passages. In this study, we analyzed the effect of TGF-β1 on and during replicative senescence of MSCs. Stimulation with TGF-β1 enhanced proliferation, induced a network like growth pattern and impaired adipogenic and osteogenic differentiation. TGF-β1 did not induce premature senescence. However, due to increased proliferation rates the cells reached replicative senescence earlier than untreated controls. This was also evident, when we analyzed senescence-associated DNA-methylation changes. Gene expression profiles of MSCs differed considerably at relatively early (P 3-5) and later passages (P 10). Nonetheless, relative gene expression differences provoked by TGF-β1 at individual time points or in a time course dependent manner (stimulation for 0, 1, 4 and 12 h) were very similar in MSCs of early and late passage. These results support the notion that TGF-β1 has major impact on MSC function, but it does not induce senescence and has similar molecular effects during culture expansion.
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Walenda
authors.forename: Khalid
authors.initials: K
authors.lastname: Abnaof
authors.forename: Sylvia
authors.initials: S
authors.lastname: Joussen
authors.forename: Steffen
authors.initials: S
authors.lastname: Meurer
authors.forename: Hubert
authors.initials: H
authors.lastname: Smeets
authors.forename: Björn
authors.initials: B
authors.lastname: Rath
authors.forename: Kurt
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Holger
authors.initials: H
authors.lastname: Fröhlich
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D019295:Computational Biology; D019175:DNA Methylation / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1