Matrix elasticity, replicative senescence and DNA methylation patterns of mesenchymal stem cells.
Matrix elasticity guides differentiation of mesenchymal stem cells (MSCs) but it is unclear if these effects are only transient - while the cells reside on the substrate - or if they reflect persistent lineage commitment. In this study, MSCs were continuously culture-expanded in parallel either on tissue culture plastic (TCP) or on polydimethylsiloxane (PDMS) gels of different elasticity to compare impact on replicative senescence, in vitro differentiation, gene expression, and DNA methylation (DNAm) profiles. The maximal number of cumulative population doublings was not affected by matrix elasticity. Differentiation towards adipogenic and osteogenic lineage was increased on soft and rigid biomaterials, respectively - but this propensity was no more evident if cells were transferred to TCP. Global gene expression profiles and DNAm profiles revealed relatively few differences in MSCs cultured on soft or rigid matrices. Furthermore, only moderate DNAm changes were observed upon culture on very soft hydrogels of human platelet lysate. Our results support the notion that matrix elasticity influences cellular behavior while the cells reside on the substrate, but it does not have major impact on cell-intrinsic lineage determination, replicative senescence or DNAm patterns.
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, Aachen 52074, Germany.
Anne
A
Schellenberg
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, Aachen 52074, Germany.
Sylvia
S
Joussen
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, Aachen 52074, Germany; Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, Jülich 52425, Germany.
Kristin
K
Moser
Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, Jülich 52425, Germany.
Nico
N
Hampe
Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, Jülich 52425, Germany.
Nils
N
Hersch
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, Aachen 52074, Germany.
Hatim
H
Hemeda
Institute of Complex Systems, ICS-8: Bioelectronics, Forschungszentrum Jülich GmbH, Jülich 52425, Germany.
Jan
J
Schnitker
Interdisciplinary Centre for Clinical Research (IZKF) Aachen, RWTH Aachen University Medical School, 52074 Aachen, Germany.
Bernd
B
Denecke
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, Aachen 52074, Germany; Institute for Biomedical Technology - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Qiong
Q
Lin
Department of Plastic and Reconstructive Surgery, RWTH Aachen University Medical School, 52074 Aachen, Germany.
Norbert
N
Pallua
Institute for Biomedical Technology - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Martin
M
Zenke
Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, Jülich 52425, Germany.
Rudolf
R
Merkel
Institute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, Jülich 52425, Germany.
Bernd
B
Hoffmann
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, Aachen 52074, Germany. Electronic address: wwagner@ukaachen.de.
Wolfgang
W
Wagner
D001792:Blood Platelets / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000494:pharmacology; D004548:Elasticity / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
D004129:Dimethylpolysiloxanes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
DNA-methylation; Elasticity; Epigenetic; Long-term culture; Mesenchymal stem cells; Platelet lysate