EMBARGOED FOR RELEASE: 27 DECEMBER 2000 AT 17:00 ET US
Contact: Laura Greer
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416-813-5046
The Hospital for Sick Children
Sick Kids' researchers discover different types of stem cells
TORONTO - A team of researchers at The Hospital for Sick Children
(HSC), led by geneticist John Dick, has discovered that distinct types of
stem cells exist within the blood system that differ in the length of time
that they can sustain a stem cell transplant. They have been termed
short-term repopulating and long-term repopulating stem cells. The
discovery of distinct types of stem cells with different functions has
important clinical implications. This research is reported in the January
issue of the scientific journal Nature Immunology.
The team developed a highly efficient method to transfer marker genes
into the human stem cells and then track the function of the marked stem
cells as they repopulated immune-deficient NOD/SCID mice. They found
that some stem cells only functioned for the first month and then
disappeared, while other stem cells only started to function after several
months, but then persisted.
"The discovery of different classes of stem cells is significant because it
gives us yet another clue on how the human blood system works," said
Dr. Dick, a senior scientist in HSC's Cancer and Blood Research Program
and a professor of Molecular and Medical Genetics at the University of
Toronto (U of T). "Because the stem cells have different functions, the
clinical use of these cells will also be different."
Stem cells make up just one in a million bone marrow cells, and are the
cells from which the entire blood system grows. Stem cell transplants, a
form of bone marrow transplants, are used widely for treating different
types of cancer, anemia and auto-immune disorders. The potential for
stem cell transplantation has exploded in recent years to include gene
therapy for a variety of genetic disorders, the use of umbilical cord
blood as a stem cell source for children, and stem cell expansion so a
small stem cell source such as cord blood may be used for adult patients.
Most applications require that stem cells function for many years
following transplantation. Therefore, the long-term repopulating stem
cells would be the ones researchers would want to target when
permanent replacement is important, such as in the development of new
treatments, like gene therapy and stem cell expansion.
However, there may also be application for the short-term repopulating
stem cells, which allow for a robust but temporary graft following a stem
cell transplant. Cancer patients often have to undergo large doses of
chemotherapy to eradicate tumours, however, this also wipes out the
vast majority of the blood system, requiring a stem cell transplant to
replace the damaged blood system as fast as possible. The short-term
repopulating cells could play an important role in rapidly generating new
blood cells until the long-term stem cells become more active. Future
research will determine if a large number of these cells could be
expanded in culture, leading possibly to more a more successful
transplant.
The discovery of two different types of stem cells has made it important
to determine how manipulations done to stem cells before
transplantation might alter them and make them more or less effective.
For example, this research has uncovered evidence that some culture
conditions being developed for gene therapy purposes can reduce long-
term repopulating stem cells, clearly an undesirable situation. Thus this
new knowledge can be used to develop the most effective conditions for
the type of stem cells that are needed for the specific application.
Stem cells are incredibly difficult to study as they look like most other
blood cells under the microscope. The only way to tell the difference is
to see them in action in a living organism as they produce bone marrow
cells. In humans, the only time this is clearly visible is following stem cell
transplantation. Given this, stem cell research involving humans is very
difficult.
Dr. Dick's research team has developed over the last 10 years a system
to reproduce the entire human blood system in mice. By transplanting
human blood cells into special immune-deficient mice called NOD/SCID
mice (which cannot reject the human cells), this system provides
scientists with a methodology to study the development of the human
blood system. This system has revolutionized the study of both normal
and leukemic human blood systems and is used in many labs worldwide.
It has aided the understanding of how stem cells function, how
abnormalities arise in leukemia, and in the development of improved
gene therapy and leukemia treatments. Dr. Dick's work in this area has
been recognized with two important medical research awards: The 1997
Michael Smith Award from the Canadian Institutes of Health Research
(CIHR), and the 2000 Robert L. Noble Prize from the National Cancer
Institute of Canada.
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The team involved in this study includes Dr. Guillermo Guenechea, a
former HSC post-doctoral fellow, Dr. Olga Gan, HSC research associate,
and Craig Dorrell, a U of T graduate student.
Funding for this research was provided by the CIHR, the NCIC with
funds from the Canadian Cancer Society, and the Canadian Genetic
Diseases Network of the National Centers of Excellence.
Additional contact:
Deborah McNorgan, Public Affairs
The Hospital for Sick Children
(416) 813-8518
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