TGF-beta1 Does Not Induce Senescence of Multipotent Mesenchymal Stromal Cells and Has Similar Effects in Early and Late Passages

Gudrun Walenda, Khalid Abnaof, Sylvia Joussen, Steffen Meurer, Hubert Smeets, Bjoern Rath, Kurt Hoffmann, Holger Froehlich, Martin Zenke, Ralf Weiskirchen, Wolfgang Wagner*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 differ considerably in cells of early and late passages. In this study, we analyzed the effect of TGF-beta 1 on and during replicative senescence of MSCs. Stimulation with TGF-beta 1 enhanced proliferation, induced a network like growth pattern and impaired adipogenic and osteogenic differentiation. TGF-beta 1 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-beta 1 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-beta 1 has major impact on MSC function, but it does not induce senescence and has similar molecular effects during culture expansion.
Original languageEnglish
JournalPLOS ONE
Volume8
Issue number10
DOIs
Publication statusPublished - 17 Oct 2013

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