05 October 2011
More than seven years after Woo Suk Hwang’s South Korean teamfraudulently claimed to have created the first cloned human embryonic stem cells (hESCs), finally the cells seem to have been made for real.
There’s one problem: the cells contain an extra set of chromosomes, which means they could never be used to grow tissues for transplantation from a patient’s own cells – the ultimate goal. But having at last shown that there is no block to making cloned human stem cells, biologists are optimistic that it should be possible to find a solution to the chromosome problem.
Dieter Egli and Scott Noggle of the New York Stem Cell Foundation Laboratory in New York City and colleagues fused skin cells with unfertilised human eggs. When they removed the eggs’ own chromosomes, as is usual in cloning experiments, the resulting embryos all stopped developing at the six to 12 cell stage.
However, when the eggs’ chromosomes were left in place, a fifth of the embryos developed further to form balls of cells called blastocysts. From two out of 13 of these embryos, the team isolated hESCs.
One of the cloned cell lines came from a man with type 1 diabetes, the other from a healthy man.
The next step
The search is now on to identify the factors associated with the egg chromosomes that allowed the embryos to develop to the blastocyst stage, says George Daley, a stem cell biologist at the Children’s Hospital in Boston, who was not involved in the research.
Once these factors are known, it should be possible to produce cloned hESCs without retaining the extra set of chromosomes. Candidate factors include various proteins already known to act as “checkpoints” for cell division.
“I don’t think this is an insurmountable biological obstacle,” says Daley. “We need to figure out what the mechanism is and complement it.”
Egli is also substituting other cells for the skin cells used in the initial experiments, to see if some will yield blastocyst embryos even when fused with eggs stripped of their chromosomes. “It could be as simple as trying other cell types,” he says.
Researchers will be keen to find the answer, given recently discovered drawbacks of induced pluripotent stem cells, or iPSCs, which are created from adult cells by a genetic reprogramming method, and seen as an alternative to cloned hESCs. Not only do iPSCs seem to be incompletely reprogrammed, retaining a “memory” of their former existence, but they may also be seen by the immune system as foreign, even when transplanted into genetically identical animals.
No eggs for free
One important reason Egli and Noggle succeeded in their experiments is that they were able to pay women to donate their eggs for research, thanks to the State of New York’s 2009 decision to allow the practice. Indeed, Egli used to work in the lab of Kevin Eggan at the Harvard Stem Cell Institute in Cambridge, Massachusetts, who this week describes his team’s abject failure to find women who were prepared to donate their eggs for free for similar experiments.
In the US, women are typically paid several thousand dollars when donating their eggs to infertile couples undergoing IVF, compensating for the time and discomfort involved. The New York team piggybacked on this process by asking women who had already decided to donate if they wanted to provide eggs for research, instead. Those who agreed were then paid the same $8000 fee given to IVF egg donors.
Approaching women who were already committed to donating their eggs “was quite creative”, says Insoo Hyun, a bioethicist at Case Western Reserve University in Cleveland, Ohio. He believes the approach reduces concerns about women being lured to donate for financial reasons. But ethical objections to the research will remain, as isolating hESCs still involves destroying a blastocyst embryo.
It may also be difficult for other groups to follow the New York team’s lead. Some ethical guidelines, including those adopted in 2005 by the US National Academy of Sciences, frown upon paid donations – and in California, paying for eggs for use in research is prohibited by law.