Keeping undifferentiated hES cells fresh
- From: "whitesickle@xxxxxxx" <whitesickle@xxxxxxx>
- Date: Fri, 17 Feb 2006 13:52:34 -0500 (EST)
UCI researchers discover key factor for survival of human embryonic
stem cells
Using neural growth factor could allow researchers to mass produce stem
cells for treatment of disease
Irvine, Calif., February 16, 2006
Human embryonic stem cells (hES) offer great hope for the treatment of
some devastating diseases, but finding a way to keep enough of these
cells usable and healthy for transplantation in patients has been an
ongoing problem. Now, scientists at UC Irvine have discovered a way to
keep large quantities of these cells alive, a finding that could
potentially lead to mass production of hES cells for therapeutic use at
lower cost.
These findings appear in a paper in the early online version of the
journal Nature Biotechnology.
UCI stem cell researchers Peter Donovan and Leslie Lock, along with
April Pyle of Johns Hopkins University, found that molecules known as
neurotrophins have a significant effect on whether hES cells survive in
the laboratory. Although stem cells have the ability to self-renew and
to differentiate into any cell in the body, it has been a challenge to
keep them alive as single cells in an undifferentiated state.
In their studies, Donovan and Lock added neurotrophins to hES cells in
the laboratory to see the effect they would have on cell survival.
Neurotrophins normally encourage the survival of tissue in the nervous
system. When three members of the family of neurotrophin growth factors
- brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3),
and neurotrophin 4 (NT-4) - were added to hES cells in culture, the
cells' survival increased 36-fold.
"Keeping hES cells alive as single cells has been extremely
difficult," Donovan said. "This fact has kept us from producing
enough cells to be useful for therapy, and has limited our ability to
genetically manipulate the cells, which we must do before they can be
transplanted into patients. It appears that if we treat hES cells with
neurotrophins, we can produce more of them faster and, hopefully, at
much lower cost."
Understanding the role that neurotrophins play in stem cell survival
could also help researchers with another major problem they face in
using hES cells for therapy. Rather than treating disease,
undifferentiated stem cells that are transplanted into the body often
form tumors instead, causing harm to the patient. A significant
challenge has been to prevent the formation of tumors by ensuring that
all cells are differentiated before they are transplanted. The studies
by Donovan and Lock show that this is even more crucial when that
transplantation is made into areas of the body rich in neurotrophins.
"Much of the research regarding stem cell therapy today focuses on
areas involving the nervous system, such as the spinal cord," Donovan
said. "Neurotrophins help the growth of tissues in those areas and
are commonly found in the nervous system. Therefore, when we use stem
cells for therapy in those areas, we must be especially careful that no
undifferentiated cells are transplanted where they could respond to
neurotrophins and form tumors." The work by Donovan and Lock
provides a potential solution to the problem. By treating stem cells in
culture with chemicals that block the action of neurotrophins on hES
cells, Donovan said, scientists can kill the undifferentiated stem
cells before they are implanted into the body.
According to Donovan, the studies also offer further proof that new
stem cell lines need to develop beyond those already in existence.
Federally approved hES lines currently used for research were not
created in the presence of growth factors such as neurotrophins. The
work undertaken by Donovan and Lock indicates that cell lines not
created in these optimal conditions may eventually mutate and lose
their usefulness for therapeutic purposes.
This study was funded through grants from the National Institutes of
Health and Johns Hopkins University.
Donovan and Lock recently joined UCI's Stem Cell Research Center,
which provides campus and visiting scientists an infrastructure to
capitalize on recent stem cell breakthroughs, particularly in the areas
of nerve repair and regeneration. In addition to holding a joint
appointment in the School of Biological Sciences and the School of
Medicine as a professor of developmental and cell biology and
biological chemistry, Donovan is interim co-director of the Stem Cell
Research Center. Lock holds appointments as assistant adjunct professor
in developmental and cell biology and in biological chemistry. The
university also is seeking support to construct a $60 million Stem Cell
Research Institute facility aimed at propelling stem cell technology
from the research lab to the clinic.
About the University of California, Irvine: The University of
California, Irvine is a top-ranked university dedicated to research,
scholarship and community service. Founded in 1965, UCI is among the
fastest-growing University of California campuses, with more than
24,000 undergraduate and graduate students and about 1,400 faculty
members. The second-largest employer in dynamic Orange County, UCI
contributes an annual economic impact of $3.3 billion. For more UCI
news, visit www.today.uci.edu.
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