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

Kurt Jacobs, Filippo Zambelli, Afroditi Mertzanidou, Ilse Julia Smolders, Mieke Geens, Ha Nguyen Thi, Lise Barbé, Karen Sermon, Claudia Spits

Onderzoeksoutput: Article

40 Citaten (Scopus)

Samenvatting

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.
Originele taal-2English
Pagina's (van-tot)330-341
Aantal pagina's12
TijdschriftStem Cell Reports
Volume6
Nummer van het tijdschrift3
Vroegere onlinedatum12 feb 2016
DOI's
StatusPublished - mrt 2016

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