Treating the injured brain and the spinal cord

Monday 11 November 2013 5:42PM (view full episode)

Professor Molly Shoichet and her colleagues at the University of Toronto specialise in regenerative medicine, designing polymers and other materials that are biologically compatible with the human body and can help deliver stem cells and drugs to the brain, the spinal cord or the retina.


Norman Swan: Still to come; your bugs, your genes and your diet.

But let's stay with the brain because Canadian research is trying to heal broken brains with high-tech bandaids. Molly Shoichet has the Canada Research Chair in Tissue Engineering at the University of Toronto.

Molly Shoichet: What we've done is developed a little patch that you can put directly on the brain, and the patch really serves as a reservoir for drugs or biomolecules to diffuse through the brain and stimulate the endogenous stem cells. Cindi Morshead's lab had shown that if you deliver two growth factors sequentially, so epidermal growth factor and then erythropoietin, each for seven days, using a mini-pump cannula system, she could stimulate the endogenous stem cells and that promoted tissue and functional repair in a rat model of stroke.

Norman Swan: So these are factors that simply make nerve cells grow and connect to the right address?

Molly Shoichet: Yes. All of us adults, we have stem cells in our brains, and these resident stem cells are stimulated by stroke itself but not stimulated sufficiently to promote repair on their own. So the idea was could we stimulate them further and promote their migration to the site of injury and use the resident stem cells to promote tissue repair?

Norman Swan: These stem cells which can be transformed into nerves live in the lining of fluid filled cavities in the brain called ventricles. So these molecules in the patches seep through to the ventricles to give the stem cells a wake-up call. It's a bit like a nicotine patch, but on the surface of the brain.

Molly Shoichet: Yes. And we engineered the patch to allow the delivery of each of the proteins sequentially. So we were able to, just with one injection…so it's an injectable gel, it's actually a really cool material because we can push it through a very fine needle…

Norman Swan: And so you call it a patch but really it's a bit of jelly.

Molly Shoichet: Yes, it's a bit of jelly. It would be like a very loose Jell-O. And so we were able to emulate the results using a much less invasive system.

Norman Swan: Is there any evidence this would work in humans?

Molly Shoichet: The big challenge in going from a mouse and a rat to a human is just the size of the brain. There are a number of different approaches that I think are possible.

Norman Swan: And the technology that you bring to the table is this ability to put drugs in other media and control how they get out.

Molly Shoichet: We designed a polymer system that would be less invasive than the current strategy.

Norman Swan: And when you say a polymer you mean a chemical that is almost like a plastic.

Molly Shoichet: Yes, but often when we think of plastics we think of hard materials. These are hydrogels. So the Jell-O analogy is a good one because Jell-O is actually a cross-linked polymer but it's a very soft and weak material. Actually a lot of the materials we used are used in food products to make food a little bit thicker, but there are long sugar chains, they are polysaccharides, and the material that we've been using here is a mixture of hyaluronan and methylcellulose. Some people might know hyaluronan or hyaluronic acid, it's used as injection into the knees for osteoarthritis. It's also used as fillers for cosmetic applications.

Norman Swan: And you've found a way of actually engineering that so that you can control how drugs get out of that. So the drugs get trapped in the polymer and you can actually plan how they get released.

Molly Shoichet: Yes, exactly.

Norman Swan: And you're working on spinal cord injury as well?

Molly Shoichet: We are. A similar idea but now we are applying a patch directly on the spinal cord, and we are going right below the dura, which is a membrane outside of the spinal cord, but we are also looking at stem cell transplantation strategies.

Norman Swan: So how are you going in animal models of spinal cord injury? What sort of results are you getting?

Molly Shoichet: What we found with some of our stem cell transplantation studies is that we are getting some tissue repair and some functional recovery. So it's very exciting. You know, when research…when you're in the trenches we take baby steps.

Norman Swan: And you work with nano-spheres, putting drugs into the tiniest little parcels.

Molly Shoichet: Right. So something that's actually fascinating with these materials is that they themselves promote tissue repair. They don't do it sufficiently for full functional recovery, but we are starting off with a material that itself has some therapeutic benefit.

Norman Swan: Really? Without any drug in it?

Molly Shoichet: Yes, it's really fascinating. We make a very small hole in the dura, and what we found is that dura heals just with the material itself, whereas with controls of just injecting a saline solution the dura doesn't heal.

Norman Swan: And what are you doing in cancer?

Molly Shoichet: Our cancer research is also a form of targeted drug delivery. In cancer we have to try to find ways to get those chemotherapeutics preferentially to the tumour. So to achieve that we have, again, designed polymers, these plastics. They are amphiphilic, so kind of like oil and water, which means they will self-assemble in water, and they will self-assemble again into these very small nano-spheres, like little beads smaller than a human hair, you can't see them by eye. And in them we incorporate those potent chemotherapeutics. And on the outside we put a targeting ligand, so kind of like a dart, that these antibodies will take those nano-spheres with the chemotherapeutic directly to the tumour tissue. So in some of our animal studies we've seen that the particle itself with the chemotherapeutic will accumulate at the tumour tissue. And then in the lab we've seen the selective cytotoxicity to cancer cells versus healthy cells.

Norman Swan: So it kills the cancer cells and leaves the others.

Molly Shoichet: Yes, it kills the cancer cells.

Norman Swan: And are these with any chemotherapy drugs or just some selected ones? There's already one on the market called Abraxane which people are using in breast cancer. What sort of drugs are you working on?

Molly Shoichet: We work with Docetaxel or Doxorubicin, but there are a lot of steps that go from the bench to the animal model to humans.

Norman Swan: And have you developed the better lip filler yet?

Molly Shoichet: [Laughs] No. But, you know, as I age I think about those more often.

Norman Swan: Molly Shoichet has the Canada Research Chair in Tissue Engineering at the University of Toronto.



Professor Molly Shoichet
Canada Research Chair in Tissue Engineering
University of Toronto


Dr Norman Swan
Brigitte Seega