One of the major concerns about growing human embryonic stem cells in the lab to generate tissues for medical therapies can now be laid to rest, suggest the results of a new study.
Among the safety fears of using human embryonic stem cells (hESCs) for therapies was that the process of “imprinting” – the switching off and on of genes during development – might be changed by growing the cells in culture rather than in the uterus.
During normal development, genes are switched on or off depending on whether they are inherited from the mother or the father of the growing organism. This is done by chemically modifying a gene, usually by adding or taking away a methyl group. This form of inheritance is known as epigenetics, and it does not alter the actual DNA sequence of a gene.
Changes in imprinting have been observed when ESCs from mice are grown in the lab. But now, a team at the University of Cambridge, UK, has become the first to show that human ESCs do not show this variability when cultured extensively.
For stem cell researchers, “this was the salient issue that had to be addressed in order to feel confident to move ahead”, says Roger Pederson, who led the study. The stability of “human ESCs was not only surprising but good news for potential therapeutic use”, he says.
“It is very important for the human stem cell field to have this [stability] demonstrated,” agrees Robin Lovell-Badge at the Medical Research Council’s National Institute for Medical Research in London, UK.
No therapeutic barrier
Pederson and colleagues examined six of the 75 genes known to be imprinted in humans in four different hESC lines. They found the genes to be stable in all cases.
Although other imprinted genes might be variable, Pederson says: “The remarkable consistency we found between four lines and with respect to six genes suggests the stability is a property of human ESCs, not just a property of these lines or genes.” The researchers conclude that the epigenetic status of cells derived from hESCs “would not be a barrier to their therapeutic use”.
Even the variability in mouse ESCs is not a huge problem, notes Lovell-Badge, because the cells actually “perform perfectly well” when transplanted.
But if the hESCs had not appeared to be so stable, far more groundwork would have needed to be done to ensure their safety, says Pederson. In particular, there would have been substantial ethical constraints with respect to transplanting them into people to see if the cells then behaved normally.
Other issues remain for stem cell safety, note the experts. One factor that would prevent any therapeutic use is any possible viral contamination from animal cells. Human ESCs were commonly grown on mouse feeder-cells which provided a structure and matrix on which the cells grow, but purity has been an issue. That problem has now been circumvented in some recent cases by using human feeder cells to grow hESCs.
