Canadian team makes stem cell breakthrough

TORONTO — A team of Canadian scientists has made a discovery about how human embryonic stem cells develop that could change the direction of research into what has been dubbed the Holy Grail of regenerative medicine.

Embryonic stem (ES) cells give rise to every tissue in the body — from the liver and heart to the bones and brain. Scientists around the world are working to understand how they might be harnessed to cure a wide variety of diseases, from growing a whole new organ to replacing brain cells damaged by Parkinson's or Alzheimer's.

In a paper published online Wednesday in the journal Nature, researchers at McMaster University say they have discovered that stem cells have a far more complex relationship with the cells around them — and that knowledge could open up entirely new avenues of research.

Previous studies in mice have shown that various types of stem cells hole up in little nests of cells known as niches, and these niches are located in specific spots within various tissues, said principal investigator Mick Bhatia, scientific director of the McMaster Stem Cell and Cancer Research Institute.

“Drawing a metaphor, a blood stem cell has a brick house located in one spot and a heart stem cell has a wood house and it's located in one spot, so it turns out that for each of these stem cells they reside very strategically in particular geography and surround themselves with a very specific kind of cell.”

“That house isn't just a place where they hang out,” Dr. Bhatia said from Hamilton. “It turns out that that house can regulate what they do.”

Working with cells in Petri dishes, his team discovered that an embryonic stem cell actually makes its own niche out of daughter cells it gives birth to, and these cells in turn “feed” their parent.

“We knew the house existed, but we certainly didn't know the person that lives in the house kept making the house, kept making the bricks,” he explained. “And we certainly didn't know that the bricks were not just protecting it, a place to be, but the person was actually feeding off the bricks.”

What the niche cells feed their parent is various types of proteins that keep the stem cells vital and growing — and possibly also help to control how that stem cell differentiates into, or gives rise to, the cells that become blood, heart, pancreas and other tissues.

“The idea of using ES cells to make blood cells we can transplant, neurons that we can transplant . . . (with) all of the techniques and technologies, we thought that we had to target the stem cell,” Dr. Bhatia said. “Now we have a new target. We can also target the niche.”

“So we now have a completely new way of controlling differentiation toward regenerative medicine.... It really opens a whole new paradigm.”

Commenting on the paper Wednesday, the head of the Stem Cell Network of Canada said the work points scientists to new pathways for producing large quantities of embryonic stem cells in the lab, and brings the notion of regenerative medicine closer to reality.

Creating any quantity of human ES cells is currently “very difficult and very expensive,” said Dr. Michael Rudnicki, director of molecular medicine and stem cell research at the Ottawa Health Research Institute.

Dr. Bhatia believes the work may also have implications for research into cancer stem cells, which appear to give rise to at least some tumour types and are resistant to chemotherapy, theoretically allowing malignancies that seemed to be cured to recur at a later time.

Conventional wisdom suggests that cancer stem cells — which have been identified in a number of malignancies, including blood and colon cancer — quietly hide in their niches for a period of time, then begin churning out daughter cells like some unstoppable Xerox machine, “which really is what a tumour is,” he said.

Dr. Bhatia suggested it may not be the cancer stem cell itself that goes awry, but the cells that make up the niche where it lives — particularly since the niche cells pump out proteins to feed their parent and may give it chemical directions for what to do.

“Maybe the niche lets go of its control. You can imagine that controlling the niche might be another target or way of controlling tumour growth.”

If the theory is correct, he said, then perhaps scientists could one day learn how to manipulate the niches to stop cancer starting in the first place.