The University’s Comprehensive Cancer Center has isolated
a gene responsible for stem-cell growth, which is used to
regenerate damaged tissues. The study found that the gene, known as
Bmi-1, is required for self-renewal, or replication, in stem cells
of the central and peripheral nervous systems.
“It was important to find the mechanism by which stem
cells can survive into adulthood,” said Ricardo Pardal, a
co-author of the study published last month.
“We found a gene involved in maintenance of stem cells
into adulthood,” he said.
Embryonic stem cells are pluripotent, he said, which means they
can differentiate into neurons, red blood cells or any other type
of tissue. In contrast, adult stem cells are tissue specific
— neural stem cells only differentiate into neural cells,
hematopoietic stem cells only turn into red blood cells and so on
for each population of stem cells. “We need stem cells
because differentiated cells have short lives,” said Pardal,
a post-doctoral medical student. Adults would die without stem cell
proliferation to supplement normal cellular replication.
The Bmi-1 gene was singled out for testing because it is known
to be a proto-onco gene that can be used to culture tumors, Pardal
said. Cancers of the blood are provoked by the hyper-proliferation
of stem cells, he said. Pardal hypothesizes that the overexpression
of the Bmi-1 gene could be the reason for metastasis in some
cancers.
“Bmi-1 came to our attention because of a prior study that
found that Bmi-1 is necessary for hematopoietic stem cells to form
red blood cells,” Anna Molofsky, a co-author of the study and
medical student, said. “So far, we and our colleagues have
studied three important types of adult stem cells and Bmi-1 appears
to work similarly in every case,” said Medical School Prof.
Sean Morrison in a written statement. Morrison conceived the
follow-up study, after having authored the first study, added,
“This raises the intriguing possibility that Bmi-1 could be a
universal regulator controlling self-renewal in all adult stem
cells.”
Unlike differentiated cells, stem cells seem to require Bmi-1 to
replicate. Morrison said his research “raises the possibility
that inappropriate activation or over-expression of Bmi-1 in stem
cells could lead to uncontrolled growth and cancer.” This
study has important consequences for cancer patients and sufferers
of neurodegenerative diseases.
“There are big implications for any therapeutic use of
stem cells,” Pardal said. We can use this gene to expand the
stem cell pool, he added. “People are excited about the
possibility of regenerative growth in the neural cells of patients
with neural diseases,” Molofsky said.
Though much media attention has focused on the possible uses of
stem cells for neural diseases, stem-cell research could also
develop new cancer therapies.
“A lot of genes that regulate stem cells regulate
cancer,” Molofsky said. “This study reinforces the
notion that stem cells and cancer cells are alike in many
ways.”
The Cancer Center lab that conducted the study was shielded from
the recent controversy over stem-cell research, Pardal said. People
in the stem cell field are turning to the use of adult stem cells
from consenting adults to avoid the ethical dilemma of using
embryonic stem cells, he added.
Central nervous system stem cells can be found in the brains of
adult subjects, and peripheral nervous system stem cells are found
in the intestine, Pardal said. Stem cells were extracted from both
these sources in lab mice for the study.
Medical research is always conducted in two ways — in
vitro and in vivo. The researchers compared the number of stem
cells in the “knockout” mouse, the test subject without
the Bmi-1 gene, to the number in a wild type mouse from the same
litter.
Molofsky and Pardal found almost no stem cells in the mutant
mouse, whose development was retarded and died within a few months.
Pardal said the lack of Bmi-1 does not kill the stem cells but
rather impairs their ability to self-replicate.
“People are very excited about stem cells and being able
to use them in therapy,” Molofsky said. “This is a
study that moves in that direction.” So far, stem cells have
not lived up to the hype over their potential therapeutic uses.
“There is a lot that needs to be learned about the basic
biology of stem cells before they can be applied to clinical
studies.”
The lab at the Cancer Center where Molofsky and Pardal conducted
the study aims to understand what happens when a person runs out of
stem cells in adulthood. One issue the lab has addressed is whether
adult stem cells can transdifferentiate, that is, transform into
cells of a different type. In another study published by the lab,
researchers offer cell fusion as an alternate explanation of this
type of behavior.