Research on cultivated cells may be flawed

Cells grown in the laboratory behave very differently from cells
in the body. Research at Linköping and Edinburgh shows that after just a few days the change is so great that it can affect the interpretation of a study.

These findings were published in the scientific journal Genome Biology.

“We took skin cells from mouse embryos, cultivated them in petri dishes and observed their gene expression over time. We were very surprised by how quickly and extensively the cells were affected. The change began almost immediately,” says Colm Nestor (pictured), researcher at the Centre for Individualized Medicine at LiU and lead author of the article.

Cells became reprogrammed

When the DNA in the original mouse cells were compared with those grown in a laboratory environment, the researchers found that the epigenome – chemical modifications that decide which genes are “on” or “off” – rapidly became reprogrammed. Over 7,000 genes were affected.

The researchers have not looked closely at the reasons for these changes, but Mr Nestor believes that one factor might be that the cells have to be squeezed onto a plastic surface instead of floating freely in the bodily fluids.

Bild på forskare som tittar på cellodlingarEven established cell lines that have been cultivated for decades – the most well-known being the cancer cells that originate from Henrietta Lacks, an American woman who died from cervical cancer in 1951 – undergo a constant change. The result is properties that are very different, compared with the cells that are to be replicated.

Research director Richard Meehan at the University of Edinburgh, cited in Bio Med Central, is now urging caution in the interpretation of a number of previous experiments. Cell models of cancer and other diseases may turn out to be deficient surrogates for in vivo biology.

Many studies still dependable

Do these new findings mean that hundreds of thousands of studies done with cultivated cells have to be called into question? No, says Mr Nestor:

“Many studies are still completely dependable. We are rather looking forward, looking to use our findings to improve existing methods. For example, we show how adding vitamin C to the cultivation medium can inhibit the epigenetic changes, and there are certainly a range of other substances that can have a positive effect.”

Article: Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems by C. E. Nestor, R. Ottaviano, D. Reinhardt, H. A. Cruickshanks, H. K. Mjoseng, R. C. McPherson, A. Lentini, J. P. Thompson, D. S. Dunican, S. Pennings, S. M. Anderton, M. Benson and R. R. Meehan. Genome Biology, 4 February 2015, DOI: 10.1186/s13059-014-0576-y

Åke Hjelm 2015-02-16

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