What is your brain, anyway?

Derek van der Kooy starts from the ground-up in applying stem cells to brain recovery

We know this — the embryo creates a brain. But how? And if you knew how, wouldn’t that help in determining how to treat brains that have been damaged through injury or illness? Similarly, we know that when we suffer a stroke, the brain is damaged to varying degrees and that those parts of the brain that are damaged, don’t recover. But why?

Derek van der Kooy’s stem cell research functions very much along these lines. Like many stem cell scientists, he picks a certain part of the body — in his case, the brain — and begins the arduous process of learning about it — from scratch.

Why does he take this approach? Because using stem cells to help an organ — say, a brain injured by a stroke or eyes that cannot see — re-gain or gain its normal function, means telling the stem cells what to do. And to do that, you need to know what the brain would know, what signals it would give to the cells in order for the brain to work.

The professor of molecular genetics and medical biophysics, who carries out his work in U of T’s Terrence Donnelly Centre for Cellular and Biomolecular Research, got his big ‘a-ha’ in the potential of brain stem cells about 20 years ago.

“Back then, people didn’t think the work we’re doing on brain stem cells was even possible. But one of our collaborators, Sam Weiss of the University of Calgary, developed this method for growing single brain stem cells from an adult mouse into these things called ‘neurospheres.’ They are floating masses of cells that come from the proliferation of a single cell.”

This discovery opened up all kinds of new information about the brain. Building on this knowledge, van der Kooy has continued to work with Weiss and U of T collaborators to delve even deeper into brain stem cells.

“One of the big things we’re interested in now is where do brains come from in the embryo? How does the embryo actually decide to produce a brain?”

To this end, van der Kooy and his team have isolated a “primitive neural stem cell that we think is the very first brain cell in the developing embryo. And we think this cell gives rise to the definitive neural stem cell, which lasts from the moment the embryo is formed right up into adulthood.”

With this foundational work, van der Kooy’s team has been able to conduct some interesting applications.

One of them is with the eye.

“The eye is known to grow out of the brain in the embryo, so this has been a natural extension of our work. The eye is actually neural tissue. We’ve been able to isolate retinal stem cells. We started our research using mice, but we have recently been able to use human adult eyes (donated when people have died to the Eye Bank of Canada). As long as we can get the eye within 24 hours of death, we can isolate 10,000 stem cells and expand them to millions of cells. That means we can grow all kinds new retinal cells from human eyes.”

And with those cells, the van der Kooy team has been able to actually restore some sight in mice that have been bred to be born blind. “We can give the mice just a miniscule amount of vision, but even that is exciting.” The team is now working with bioengineers at U of T to see if they can restore more sight.

The essence of this work — and that of stem cell research and application in general — is that it means scientists have to do the most difficult task imaginable — truly understand the genius of nature in creating this force we call life.

Doesn’t that intimidate van der Kooy?

“It doesn’t so much intimidate me — my reaction is always more of wonder and amazement at the complexity of living systems. Actually, the hard part is the need for good ideas. So, we have these cells, what are we going to do with them? What are the questions we need to ask? That is the challenge.”