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About SickKids

November 4, 2007

New Territory Mapped in Stem Cell Transplantation

TORONTO – Transplant research has taken another step forward at The Hospital for Sick Children (SickKids) where scientists have discovered a gene with properties that allow for the successful engraftment of stem cells from human bone marrow into mice. Researchers hope further studies will lead to the development of a therapy so more children with blood diseases can receive bone marrow transplantation.

The discovery was made by Dr. Jayne Danska, senior scientist with SickKids Research Institute and professor of Immunology and Medical Biophysics at the University of Toronto, in collaboration with Dr. John Dick, senior scientist at Ontario Cancer Institute, the research arm of Princess Margaret Hospital, member of the McEwen Center for Regenerative Medicine and professor in the Department Molecular and Medical Genetics at the University of Toronto. Their research is reported in the November 4 th online issue of Nature Immunology .

Danska's lab investigates the causes of autoimmune diabetes and lymphoblastic leukemia, while Dick's lab focuses on human blood stem cells and leukemia. During discussions about their work, Dick observed that one of the mouse strains, which he used for human stem cell research and which Danska studied because it is prone to diabetes, was the only mouse strain in which transplanted human blood stem cells could engraft and develop. Together they decided to investigate the genetic basis for this capacity, and they identified the gene, SIRPalpha, as the one responsible for support of human blood cell engraftment and growth. They also identified the type of cell that expresses SIRPalpha and is responsible for either destroying or supporting growth of human blood stem cells.

“We have the gene, we have the cell type in which it functions, and we know the variations in the gene that confer the special effect,” says Danska.

To get a view of the gene in a human population, the research team conducted a DNA sequencing of individuals from four different ethnic and racial populations. “We found a striking diversity,” Danska explains. “There were 10 different types of this gene among just 37 individuals. Some of the specific variations that we found in humans line up with the positions of the gene that we found to be responsible for human stem cell support in the mouse transplant setting – they're in exactly the same parts of the gene.”

The gene discovery is important in several ways. For one thing, scientists are hoping it will lead to the development of a therapy that would mimic the effects of SIRPalpha and create conditions for a successful bone marrow transplant. Also, the identification of this gene may help provide a genetic test that could be applied to blood stem cell donors and recipients to increase opportunities for successful transplants.

“Genes that control stem cells could also play a role in other blood disease processes like leukemia and anemia,” says Dick. “So we will also investigate whether SIRPalpha plays a broader role in these human diseases.”

Danska and colleagues at SickKids and other hospitals have begun an investigation of the SIRPalpha gene in thousands of human bone marrow transplant donor and recipient pairs, to test the relationship between the gene variation and transplantation outcomes.

Dr. Adam Gassas and other members of the Blood and Marrow Transplantation Program at SickKids also hope to collaborate with Danska on further research. “This discovery may in future play an important role in choosing the best donor for stem cell transplantation to improve outcome,” he says.

Funding for the research was provided by the Juvenile Diabetes Research Foundation, Genome Canada/Ontario Genomics Institute, the Canadian Institutes of Health Research, the Leukemia and Lymphoma Society, and the Province of Ontario 's Ministry of Research and Innovation through the Ontario Institute for Cancer Research.

SickKids, affiliated with the University of Toronto , is Canada 's most research-intensive children's hospital and the largest centre dedicated to improving children's health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. The mission of SickKids is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

Jane Finlayson
University Health Network

For more information, please contact:

Shelley Romoff
Public Affairs
The Hospital for Sick Children
Phone: 416-813-5046
email: shelley.romoff@sickkids.ca