Italian stem cell researchers have discovered a new “master control
gene” for human blood stem cells and found that manipulating its levels
could potentially create a way to expand these cells for clinical use.
The findings, published today online ahead of print in Cell Stem
Cell, usher in a new paradigm for the regulation of human blood stem
cells, says co-principal investigator Dr. John Dick, who holds a Canada
Research Chair in Stem Cell Biology and is a Senior Scientist at
University Health Network’s McEwen Centre for Regenerative Medicine and
Ontario Cancer Institute (OCI), the research arm of the Princess
Margaret Cancer Centre. He is also a Professor in the Department of
Molecular Genetics, University of Toronto.
“For the first time in human blood stem cells, we have established
that a new class of non-coding RNA called miRNA represents a new tactic
for manipulating these cells, which opens the door to expanding them for
therapeutic uses,” says Dr. Dick.
In 2011, Dr. Dick isolated a human blood stem cell in its purest form
– as a single stem cell capable of regenerating the entire blood system
– paving the way for clinical uses. He also pioneered the cancer stem
cell field by identifying leukemia stem cells in 1994 and colon cancer
stem cells in 2007.
OCI lead author Dr. Eric Lechman says the research team removed a
master control gene – microRNA 126 (miR-126) – that normally governs
the expression of hundreds of other genes by keeping them silenced,
which in turn keeps the stem cells in a non-dividing dormant state. The
method was to introduce excess numbers of miR-126 binding sites into the
stem cells by using a specially designed viral vector.
“The virus acted like a sponge and mopped up the specific miRNA in
the cells. This enabled the expression of normally repressed genes to
become prominent, after which we observed a long-term expansion of the
blood stem cells without exhaustion or malignant transformation,” says
Adds Dr. Dick: “We’ve shown that if you remove the miRNA you can
expand the stem cells while keeping their identity intact. That’s the
key to long-term stem cell expansion for use with patients.” The
co-principal investigator was Dr. Luigi Naldini, Director, of the San
Raffaele Telethon Institute for Gene Therapy, Milan.
Dr. Dick’s research was funded by the Canadian Institutes of Health
Research, the Canadian Cancer Society, the Terry Fox Foundation, Genome
Canada through the Ontario Genomics Institute, the Ontario Institute for
Cancer Research, the Canada Research Chair Program, the Ontario
Ministry of Health and Long-Term Care, the Canada Foundation of
Innovation, as well as The Princess Margaret Cancer Foundation.
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About Princess Margaret Cancer Centre, University Health Network
Princess Margaret Cancer Centre and its research arm, Ontario Cancer
Institute, have achieved an international reputation as global leaders
in the fight against cancer and delivering personalized cancer medicine.
The Princess Margaret, one of the top five international cancer
research centres, is a member of the University Health Network, which
also includes Toronto General Hospital, Toronto Western Hospital and
Toronto Rehabilitation Institute. All are research hospitals affiliated
with the University of Toronto. For more information, go to www.theprincessmargaret.ca or www.uhn.ca.
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