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Stem Cell Reports. 2016 Mar 8;6(3):330-41. doi: 10.1016/j.stemcr.2016.01.015. Epub 2016 Feb 25.

Higher-Density Culture in Human Embryonic Stem Cells Results in DNA Damage and Genome Instability.

Author information

1
Research Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium; Institute of Molecular Cancer Research, University of Zurich (UZH), Winterthurerstrasse 190, 8057 Zurich, Switzerland.
2
Research Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
3
Research Group Experimental Neuropharmacology, Center for Neurosciences C4N, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
4
Research Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium; Center for Molecular Biology, Institute of Research and Development, Duy Tan University, K7/25 Quang Trung, Danang 550000, Vietnam.
5
Research Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: claudia.spits@vub.ac.be.

Abstract

Human embryonic stem cells (hESC) show great promise for clinical and research applications, but their well-known proneness to genomic instability hampers the development to their full potential. Here, we demonstrate that medium acidification linked to culture density is the main cause of DNA damage and genomic alterations in hESC grown on feeder layers, and this even in the short time span of a single passage. In line with this, we show that increasing the frequency of the medium refreshments minimizes the levels of DNA damage and genetic instability. Also, we show that cells cultured on laminin-521 do not present this increase in DNA damage when grown at high density, although the (long-term) impact on their genomic stability remains to be elucidated. Our results explain the high levels of genome instability observed over the years by many laboratories worldwide, and show that the development of optimal culture conditions is key to solving this problem.

PMID:
26923824
PMCID:
PMC4788786
DOI:
10.1016/j.stemcr.2016.01.015
[Indexed for MEDLINE]
Free PMC Article

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