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. 2011 May 10;6(5):e19503. doi: 10.1371/journal.pone.0019503

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So 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 properly credited.

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(a) MSCs undergo replicative senescence upon repeated (more than 15 passages) subculturing in vitro, as shown by SA β-gal staining. (b) Proliferation rates of MSCs in early and late passages were measured by MTT assay. (c–d) The expression of DNMT1, DNMT3A and DNMT3B was down-regulated, whereas p16^INK4A was up-regulated during repeated subculture-induced senescence of MSCs, as shown by real-time qPCR (c) and immunoblot analysis (d). * and ** represent statistical significance at the levels of p<0.05 and p<0.01, respectively.