Monday, July 16, 2012

World - Debate over existence of ovarian stem cells heats up

Are women born with all the eggs they will ever have, or do they possess the ability to make more?

That debate is in full force this week as researchers led by Kui Liu at the University of Gothenburg in Sweden say they have ruled out the tantalising possibility that ovarian stem cells exist.

Back in February, Jonathan Tilly and his colleagues at Massachusetts General Hospital in Boston claimed that they had found stem cells in human ovaries. The news was incredible – the cells were able to form new immature eggs, and it was hoped that they could be harnessed to improve in vitro fertilisation and help older women to conceive a healthy baby.

But it hasn't been easy to overturn the dogma that women are born with all the eggs that they will ever have.

Brand new eggs

The human ovary contains up to 2 million immature eggs, and every month one of these matures and is released. It has been long-held that mammals are born with their lifetime's supply of eggs. That was until Tilly and various other groups discovered what they believed to be stem cells in mouse ovaries. The groups said that these cells were able to divide into new egg cells.

As these ovarian stem cells mature, a protein called vasa gets pulled from the surface of the cell into the centre, says Tilly. So his team looked for cells with vasa still on their surface in human ovarian tissue.

They found a small number and identified them as stem cells because when they were removed from the tissue and placed inside a mouse, they divided into new cells capable of forming early-stage eggs.

Liu's team used a different approach. They used a mouse genetically modified to make all its cells glow green. They bred this mouse with another transgenic mouse that carries a piece of DNA that recognises vasa and changes the colour of only those cells that carry it. As a result, all of their offsprings' cells are green except those containing vasa, which appear red, yellow or blue.

The group monitored the cells that weren't green for three days. "These cells never proliferate," says Liu. What's more, when his team injected the non-green cells into a piece of mouse ovary, they were not able to make eggs.

"We've found that these cells are not really stem cells," says Liu. While the cells might look like stem cells, they don't act in the same way, he says. "We're not sure what they are."

Tilly stands by his discovery. He points out that it is difficult for Liu's team to rule out his findings because they did not use the same technique.

A different view

The gene for vasa is expressed in cells at every stage of development, Tilly says. This might mean that the cells that Liu's team tried to develop did not include any stem cells, which are rare, he says.

The cells that Liu’s team found were also about three or four time the size of those that Tilly's team identified as stem cells. "From the results shown, Liu was working with nothing but immature eggs, and of course they're not going to proliferate," says Tilly.

He thinks Liu's team might have spotted some stem cells if they had monitored the cells samples for longer. "It takes several weeks for the cells to start growing, not three days," he says.

Evelyn Telfer at the University of Edinburgh, UK, is also unconvinced by Liu's findings. "They simply do not attempt to look at the population of cells reported by the other group," she says. "They're not comparing like-for-like, they're comparing apples and oranges." Although the role of the stem-like cells that Tilly's group identified still needs to be proven, Liu's team's findings don't rule out the cells' existence, says Telfer.

Hugh Clarke at McGill University in Canada, however, is impressed with Liu's study. "It's a really good study that's carefully done," he says. "It provides evidence that ovarian stem cells don't exist."
Instead of settling the debate, the new findings may only have fanned the flames. "Multiple groups have found these [stem] cells in multiple species and yet there are still people who refuse to believe it," says Tilly.

"I suggest we try to calm down the hype," says Liu. "We need to wait for other labs to repeat [Tilly's] findings before we throw money into this."

"I wouldn't waste time looking for something that I don't think is there," says Clarke.

Tilly, however, doesn't mind if other groups give up, because then, he says, the most exciting discoveries of what the cells can do will be left to him and his colleagues.

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