Drug boosts stem cells in cord blood for transfusing cancer patients: study

TORONTO (CP) - An experimental drug already being tested in patients with diabetes and Alzheimer's disease has been found to boost the number of stem cells from umbilical cord blood, allowing them to more quickly regenerate the blood system, Canadian researchers have found.

The drug, which shuts down a molecule called GSK-3, was found to triple the number of stem cells when human cord blood was injected into mice that had had their immune systems destroyed by radiation.

These stem cells quickly gave birth to the many different types of cells that make up the blood of all mammals - from oxygen-carrying red blood cells to the white blood cells that are part of the body's immune system.

"This is the first drug used to expand a stem cell population in vivo (within a living body)," as opposed to culturing them in a laboratory, said senior researcher Mick Bhatia, director of stem cell biology at the Robarts Research Institute at the University of Western Ontario.

While the research involved mice, Bhatia believes doctors could immediately begin testing the GSK-3 inhibitor in humans because the drug has already been proven safe in people with Type 2 diabetes (it works by controlling blood sugar) and in those with Alzheimer's and Parkinson's disease.

The aim would be to help patients with cancer of the solid organs, such as the liver, who are unable to tolerate sufficiently aggressive bouts of chemotherapy and radiation to destroy their tumour because the treatment also harms fast-dividing cells in the blood, leaving them open to life-threatening infections.

One way to help overcome that problem is to perform a bone marrow transplant (if a donor match can be found) or to inject stem cells from blood from the umbilical cord of a baby, donated by the parents after the child's birth. (These are not stem cells from donated embryos, a type of research banned in Canada.)

"Normally cord blood would not be enough," Bhatia said from London, Ont. "It's a little volume of cord blood - little baby, big person. You don't get enough regeneration.

"GSK-3 inhibitor presses the accelerator on those cord blood stem cells . . . Instead of producing five cells, we can make it produce 15 cells.

"What that means is that for every cord blood sample collected, there are a far greater number of people that could benefit and be transplanted with those cells."

The research, published in this month's issue of Nature Medicine, involved immune-deficient laboratory mice that had been given transplants of stem cells from human cord blood or adult bone marrow, then injected twice a week over three months with GSK-3 inhibitor.

The stem cells created a robust new blood system, while maintaining the original pool of stem cells and extending survival of the mice by 60 to 90 per cent, researchers found.

Calling the finding "tremendously exciting," Dr. Michael Rudnicki said the ability to regenerate the blood system from stem cells in patients using a drug instead of first having to bioengineer them in the lab would be easier and cheaper.

"It's an important finding, where (Bhatia's) put two and two together to get 25. He's moved the field forward in an important way," Rudnicki, scientific director of the Stem Cell Network of Canada, said from Ottawa.

Dr. Janet Rossant, chief of research at Toronto's Hospital for Sick Children and a noted stem cell scientist, agreed the work is a move forward that would "improve the take of stem cells transplantations."

"It's a step - but not there yet - towards the Holy Grail," Rossant said. "The Holy Grail is to be able to take stem cells from cord blood or stem cells from bone marrow and be able to grow them in culture in large numbers so you'd actually not have a limiting resource."

The ultimate dream of medicine is to be able to manipulate stem cells - the building-blocks from which all the mature cells of the body arise - to regenerate heart, lung, brain and other tissues to repair damage from disease or injury.

Bhatia wants to form collaborations with other scientists to see if the molecule GSK-3 controls more than stem cells in the blood and may affect stem cells in other tissues - with the goal of producing nerve cells that could regenerate spinal cord tissue or brain cells destroyed by a stroke, for instance.

He said science always talks about the promise of stem cells and what they may make possible in the future.

But the GSK-3 inhibitor is something that could be put into practice now to see if it would improve patients' health, he said.

"This promissory note about stem cells is coming, and this is an example."