Matrix elasticity, replicative senescence and DNA methylation patterns of mesenchymal stem cells

Schellenberg, Anne; Joussen, Sylvia; Moser, Kristin; Hampe, Nico; Hersch, Nils; Hemeda, Hatim; Schnitker, Jan; Denecke, Bernd; Lin, Qiong; Pallua, Norbert; Zenke, Martin; Merkel, Rudolf; Hoffmann, Bernd; Wagner, Wolfgang

doi:10.1016/j.biomaterials.2014.04.079

Cited by 65 publications

(60 citation statements)

References 61 publications

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“…Substrate elasticity has been proposed as critical factor in directing lineage-specification of MSCs [5]. However, we have recently described that stiffness affects cells only while organized on the matrix and does not induce epigenetic changes in the DNA methylation pattern [6]. In this study we used polyimide, a commercially available plastic polymer that has been employed in retinal and neuronal implants [57,58].…”

Section: Discussionmentioning

confidence: 98%

“…In their physiological microenvironment, the so called "stem cell niche", mechanical stimuli are provided by the extra cellular matrix (ECM) as well as cellecell interactions and contribute to cell fate decisions [4]. Cells can "sense" substrate elasticity [5,6] and surface patterns ranging from 10 nm to 100 mm [7,8]. This recognition is particularly mediated by integrin receptors [9e11], which in combination with several other proteins like vinculin or zyxin form focal adhesions [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages

et al. 2015

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages

et al. 2015

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“…To mimic the replicative senescence seen in MSCs [36, 37], we adopted a new approach by chronically exposing cells to low oxidative stress and a low serum environment. Specifically, HMSCs at passages 3–5 at approximately 50% confluence were continuously exposed to low concentration of hydrogen peroxide (50 µ M H 2 O 2 ) in DMEM supplemented with 5% FBS.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

Pian

et al. 2017

Stem Cells International

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Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal). By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B) also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.

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“…demonstrated that neural differentiation of MSCs promoted by soft surfaces could be reversed simply by transferring the cells from a soft to stiff surface 49 . Additionally, MSCs grown on soft surfaces do not appear to alter their global DNA methylation patterns suggesting that the changes in gene expression while on soft surfaces is a transient effect 50 . Thus, not surprisingly, the cell background is largely important in how the cell responds to very soft surfaces.…”

Section: Introductionmentioning

confidence: 99%

Signal transduction of the physical environment in the neural differentiation of stem cells

Thompson¹,

Chan

2016

Technology

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Neural differentiation is largely dependent on extracellular signals within the cell microenvironment. These extracellular signals are mainly in the form of soluble factors that activate intracellular signaling cascades that drive changes in the cell nucleus. However, it is becoming increasingly apparent that the physical microenvironment provides signals that can also influence lineage commitment and very low modulus surfaces has been repeatedly demonstrated to promote neurogenesis. The molecular mechanisms governing mechano-induced neural differentiation are still largely uncharacterized; however, a growing body of evidence indicates that physical stimuli can regulate known signaling cascades and transcription factors involved in neural differentiation. Understanding how the physical environment affects neural differentiation at the molecular level will enable research and design of materials that will eventually enhance neural stem cell (NSC) differentiation, homogeneity and specificity.

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Matrix elasticity, replicative senescence and DNA methylation patterns of mesenchymal stem cells

Cited by 65 publications

References 61 publications

Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages

Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages

Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

Signal transduction of the physical environment in the neural differentiation of stem cells

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