5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation

Xueying Yan; Sabrina Ehnert; Mihaela Culmes; Anastasia Bachmann; Claudine Seeliger; Lilianna Schyschka; Zhiyong Wang; Afshin Rahmanian-Schwarz; Ulrich Stöckle; Paul A De Sousa; Jaroslav Pelisek; Andreas K Nussler

doi:10.1371/journal.pone.0090846

5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation

Xueying Yan, Sabrina Ehnert, Mihaela Culmes, Anastasia Bachmann, Claudine Seeliger, Lilianna Schyschka, Zhiyong Wang, Afshin Rahmanian-Schwarz, Ulrich Stöckle, Paul A De Sousa, Jaroslav Pelisek, Andreas K Nussler

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Abstract / Description of output

The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (

Original language	English
Pages (from-to)	e90846
Journal	PLoS ONE
Volume	9
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0090846
Publication status	Published - 6 Mar 2014

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10.1371/journal.pone.0090846

5-Azacytidine Improves the Osteogenic Differentiation Potential of Aged Human Adipose-Derived Mesenchymal Stem Cells by DNA Demethylation
Copyright: © 2014 Yan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Final published version, 5.88 MBLicence: Creative Commons: Attribution (CC-BY)

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0090846

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Yan, X., Ehnert, S., Culmes, M., Bachmann, A., Seeliger, C., Schyschka, L., Wang, Z., Rahmanian-Schwarz, A., Stöckle, U., De Sousa, P. A., Pelisek, J., & Nussler, A. K. (2014). 5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation. PLoS ONE, 9(3), e90846. https://doi.org/10.1371/journal.pone.0090846

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abstract = "The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (",

author = "Xueying Yan and Sabrina Ehnert and Mihaela Culmes and Anastasia Bachmann and Claudine Seeliger and Lilianna Schyschka and Zhiyong Wang and Afshin Rahmanian-Schwarz and Ulrich St{\"o}ckle and {De Sousa}, {Paul A} and Jaroslav Pelisek and Nussler, {Andreas K}",

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Yan, X, Ehnert, S, Culmes, M, Bachmann, A, Seeliger, C, Schyschka, L, Wang, Z, Rahmanian-Schwarz, A, Stöckle, U, De Sousa, PA, Pelisek, J & Nussler, AK 2014, '5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation', PLoS ONE, vol. 9, no. 3, pp. e90846. https://doi.org/10.1371/journal.pone.0090846

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T1 - 5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation

AU - Yan, Xueying

AU - Ehnert, Sabrina

AU - Culmes, Mihaela

AU - Bachmann, Anastasia

AU - Seeliger, Claudine

AU - Schyschka, Lilianna

AU - Wang, Zhiyong

AU - Rahmanian-Schwarz, Afshin

AU - Stöckle, Ulrich

AU - De Sousa, Paul A

AU - Pelisek, Jaroslav

AU - Nussler, Andreas K

PY - 2014/3/6

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N2 - The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (

AB - The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (

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DO - 10.1371/journal.pone.0090846

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JO - PLoS ONE

JF - PLoS ONE

IS - 3

ER -

5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation

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