Offers hope for blood treatments, embryo controversy
April 2, 2002
VANCOUVER - A Canadian team's stem cell "breakthrough" could one day lead to powerful new treatments for leukemia and other blood diseases and eliminate the need for bone marrow transplants.
The researchers discovered how to "supercharge" adult stem cells taken from the blood and mass-produce them in the lab. The discovery is being announced today by the B.C. Cancer Agency.
As evidence of the enormous potential of the discovery, the agency points to an experiment involving mice at the Terry Fox Lab in Vancouver. The mice had their blood systems destroyed by radiation and then rebuilt using blood stem cells grown in the lab.
"They're now perfectly healthy," said Dr. Keith Humphries, the UBC professor who heads the team at the cancer agency.
"They're now perfectly healthy," said Dr. Keith Humphries, the University of British Columbia professor who heads the team at the cancer agency.
Blood stem cells, also known as hematopoietic stem cells, give rise to all the cells in the blood system. Because these stem cells are so rare, it is difficult to obtain enough from natural sources, such as umbilical cord blood or bone marrow, to treat people whose blood has been ravaged by diseases such as cancer or radiation.
Researchers have long dreamed of growing blood stem cells in the lab to treat disease and mass-produce blood products. But the cells have proven next to impossible to grow outside the body.
Dr. Humphries and his colleagues at the University of British Columbia got over the hurdle by "supercharging" the cells with a gene called HOXB4. They inserted a copy of the gene in adult blood stem cells and were amazed to see the cells grow and multiply at unprecedented rates.
"We're getting 40- to 100-fold increases," said Dr. Humphries, whose Vancouver group collaborated with Dr. Guy Sauvageau at the Université de Montréal to engineer the gene into the cells. The scientists detail the work in the April 5 edition of the journal Cell.
While the HOXB4-enhanced cells multiply at extraordinary rates in the lab, Dr. Humphries said they behave normally when injected into mice. The cells turn into normal blood cells and go about their business.
"There is no evidence the daughter cells are abnormal in any way," he said. The experimental mice "rescued" by the cells in the last two years have led long, normal lives.
The HOXB4 gene appears to be involved solely in the multiplication of stem cells, Dr. Humphries said. It seems to turn off once the cells differentiate into white or red blood cells.
While most of the researchers' work was done on mouse blood stem cells, they have also shown HOXB4 can stimulate production of human blood stem cells, said Dr Humphries, who credits his graduate student Jennifer Antonchuk with much of the work.
Dr. Humphries, who was a member of the advisory committee that helped draft the Canadian guidelines for research on stem cells released last month, said the findings help affirm the promise of adult stem cells, which are much less controversial than the variety created by killing days-old embryos. The embryonic stem cells can morph into any type of cell found in the body, while adult stem cells are less malleable.
Dr. Humphries and his colleagues say the research on HOXB4 stem cells shows great promise, but they caution that they are not about to start injecting the genetically "supercharged" blood stem cells into people.
Scientists must first understand the biochemical process HOXB4 uses to get the cells to grow; then they must learn how to control the potent "genetic throttle."
Ideally, he said, they would like to be able to simply "tickle" the human blood stem cells using growth factors the HOXB4 gene produces. This would circumvent the need to insert genetically altered cells into the body.
HOXB4 is from a family of intriguing genes that help control how stem cells multiply and develop, Dr. Humphries said. By tweaking some of the genes from the family, researchers have been able to grow flies with four wings instead of two, and legs on their heads instead of antennae. Some of the genes are also known to behave abnormally in blood cancers, which is what attracted Dr. Humphries to the genes.
HOXB4 appears to be a harmless gene, he said, but added that one needs
to be very sure before starting any experiments on people.
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