New Territory Mapped in Stem Cell Transplantation



    TORONTO, Nov. 4 /CNW/ - 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 4th 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 further information:

For further information: Shelley Romoff, The Hospital for Sick Children,
(416) 813-5046, shelley.romoff@sickkids.ca; Jane Finlayson, University Health
Network, (416) 946-2846, jane.finlayson@uhn.on.ca

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