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Past Winner
2005 E.W.R. Steacie Memorial Fellowship

Peter Zandstra

Bioengineering

University of Toronto


Peter Zandstra
Peter Zandstra

Want to create life-saving stem cell therapies? Before hitting the OR, it's going to be necessary to think like an engineer, says stem cell bioengineer Dr. Peter Zandstra, one of six winners of the 2005 NSERC E.W.R. Steacie Memorial Fellowship.

Big Idea: "We're answering questions that are fundamentally important to the success of stem cell therapies," says Dr. Zandstra, who holds the Canada Research Chair in Stem Cell Bioengineering at the University of Toronto.

"At the end of the day, if you're going to use these cells to cure a disease you're going to have to be able to strictly control their growth and how they mature, while generating enough of them to be able to actually treat the disease."

The Question: How do you use stem cells to grow large numbers of specific tissue cells, like those of the heart or blood? Since the headline-making discovery of the first human embryonic stem cells in 1998, there's been ongoing public buzz about the potential curative powers of these primitive cells.

But embryonic stem cell-derived cell transplants and gene therapies are still a long way from saving lives. One key hurdle is that, until recently, researchers could only generate functionally useful cells from embryonic stem cells in tiny droplets smaller than a drip from a kitchen faucet.

And in many cases, only one-in-a-hundred of the cells actually developed into the desired cell type. These levels of production are too small and inefficient to produce clinically useful numbers of cells. "We know that stem cells have the potential to do what we need them to do," says Dr. Zandstra. "The challenge is to understand how to control their development so that we can coax this behaviour in a flask."

Research at the Edge: For the past decade, Dr. Zandstra has been working to rev up the production of stem cells and their descendants. The raw materials are adult blood stem cells and embryonic stem cells. The end products are blood and heart cells – lots of them. Enough mouse heart cells that they form beating tissue. Enough blood cells that one day they could boost the blood supply of an immuno-compromised patient. To do this, he has been applying engineering principles to stem cell research.

Central to this approach has been the creation of detailed computational models of stem cell growth and differentiation, the process by which a stem cell matures into its final adult form.

"If you describe something mathematically you have a much better understanding of it than if you just observe it," he says. "And it's also a powerful way to test many different hypotheses in silico before going into the lab and doing the difficult experiment."

Based on this research, Dr. Zandstra has pioneered the ability to grow stem cells in bioreactors, tissue culture vessels wherein the cells' environment is tightly regulated.

The Next Step: Dr. Zandstra's NSERC Steacie Fellowship will enable his impressive 15-person lab to take a critical next step: extending their research from mouse to man.

"We have a bioreactor in the lab that can now generate lots of mouse cardiac cells, but there's only so much we can do with mouse cells. Now if we can also figure out how to get human embryonic stem cells to differentiate on command to generate functional adult-like cells you can begin to think about the kinds of medical conditions you could treat with them," says Dr. Zandstra. He notes that researchers presently have a much better understanding of what's required to grow mouse stem cells than human ones.

To improve this he'll be advancing his computer models of stem cell growth and differentiation, and experimentally exploring how the location, nutrient supply and communication of human embryonic stem cells effects the types of cells they generate. His lab will be using a technique Dr. Zandstra invented in which the differentiation of embryonic stem cells is closely controlled by growing them in bioengineered hydrogel microcapsules. In this way the nutrients and environmental conditions the cells experience can be tightly regulated, thus guiding their development.

The human embryonic stem cells he'll use will be obtained from stem cell lines approved by the Canadian Stem Cell Oversight Committee.