Sunday, April 16, 2006

Stem cells may help our bodies heal themselves

Research aimed at degenerative diseases Labs across Canada take part in effort
Apr. 6, 2006. 01:00 AM
ELAINE CAREY
TORONTO STAR STAFF REPORTER



Janet Rossant's stem-cell research may one day help our bodies heal themselves.

As chief of research at The Hospital for Sick Children, Rossant is collaborating with labs across Canada to see whether human embryonic stem cells can be useful tools for treating degenerative diseases. Her lab at Sick Kids is looking at trying to get stem cells to form blood vessels that could be transplanted into the damaged tissue of patients with heart disease.

Stem cells have become a crucial area of research at the hospital, as investigators try to use them to understand and fight a variety of diseases.

Rossant is the award-winning discoverer of early cells that form the human placenta. She showed several years ago that you can generate mice entirely derived from embryonic stem cells, provided you mix them with a normal embryo.

"It's still an amazing thing to think about," she says. "You can actually take cells, put them in a Petri dish and genetically alter them to create genetically altered mice."

Those mice are created to mimic human diseases. Mice produce only two types of cells: a group that forms the placenta, and a group of about 15 cells called the inner cell mass that forms the mouse itself.

Rossant's team has been able to develop stem cells from both types of mouse cells, "which gives us enormous biological tools to study these two lineages," she says. "We're using it to understand how the embryo makes the decision to make either a very potent cell or a placental cell."

Her research is moving into the more controversial area of using human embryonic stem cells from stem-cell lines approved for use in Canada, to see whether the same mechanisms are at work as in the mouse.

"At this stage, we're still at the exploratory phase where we need to understand the power of stem cells, how best to grow them in culture and keep them normal, which is one of the critical issues," she says.

If the information they derive from embryonic stem cells can be applied to adult ones, they could be grown in culture and would become important tools for understanding human biology and developing new drug targets that can interfere with stem-cell survival.

"Then stem cells themselves won't be used in therapy but we will use the information to help drive our own bodies to fix themselves," she says.

"That's certainly the long, long-term goal."

Freda Miller's lab has shown that stem cells found in adult skin retain the capacity to make many different types of cells. Now it's focused on using these cells to find ways of treating devastating diseases of the nervous system, and also spinal cord trauma.

The work began because the only human source for brain stem cells is either aborted fetuses or human embryonic stem cell lines. While Canadians have agreed it's ethically acceptable to use them, "I think most people would prefer not to if they didn't have to," she says.

Even using those cells, "You're talking about putting cells into people that don't belong to them," she says. "If we had a 17-year-old spinal cord injury victim and we could show they could be treated with stem cells, then we would probably be faced with immuno-suppressing him for the rest of his life."

Her lab is trying to find a source of stem cells that come from thepatients themselves and that come from adult tissue so they won't have to deal with the ethical issues of using embryos.

"What we have now is this population of human cells that can make multiple kinds of cells, including cells involved in the nervous system," she says. "Now we're asking: `Are they functional, can we put them back in the animal?'"


One of the cells produces myelin, the sheath that wraps around most of the nerves in the body and that's lost in multiple sclerosis and many traumatic brain and spinal cord injuries.


The lab, in collaboration with the Rick Hansen Centre for spinal cord injury research in British Columbia, has shown that you can put those cells in animals and they produce functional myelin that encourages the growth of nerve cells that have been damaged and injured.

"We're very excited. It looks like our cells can do everything we hoped they could do," she says. While the work is all in animal models, the next step is to try it on humans.


Dr. Peter Dirks' lab made the breakthrough discovery that a small number of cells in a brain tumour control its growth. They have been able to take those cells, inject them into mice and replicate the human brain tumour. That has led to research to define what those cells are and what drugs can be used to destroy them.

"Based on our work, this idea has really caught on and many groups all over the world are thinking about brain tumours in this way so that's pretty exciting," Dirks says.

Brain tumours are hard to treat because radiation can only be given in limited doses or it kills the surrounding brain cells, causing long-term cognitive damage. Even with measured doses, it has serious effects on learning and memory function — even in children — over time, he says.

"With chemotherapy, the brain is a relatively privileged site," he says. "It's designed not to allow drugs or other substances into its milieu, so even to get a chemotherapy agent that can get into the brain and have a chance of being effective, is difficult.

"We really need to find treatment that's more selective and that's going to be another big challenge — how to target tumour cells as opposed to normal stem cells in the brain.

``At this point, we don't even know what stem cells are doing in our brain but their mere presence suggests they can go bad to form a brain tumour. But it may be a completely different cell that initiates that in a child and an adult."

Work on cancer stem cells is being hotly pursued in almost every type of human cancer, he says.

"That's the real challenge now, to figure out what makes them tick and how to shut them down. We have to find the tumour cells that really matter."

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