Posted by
Tia Ghose
[Entry posted at 18th February 2009 01:24 AM GMT
http://www.the-scientist.com/templates/trackable/display/blog.jsp?type=blog&o_url=blog/display/55430&id=55430
A neural stem cell transplant from fetal cells performed in Russia led to a
brain tumor in a teenage boy, researchers in this week's PLoS Medicine
report, raising concerns about the safety of neural stem cells
treatments.
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MRI of brain lesion, courtesy of PLoS
Medicine |
The researchers confirmed that the cancer originated from the donor tissue,
not the boy's own cells. This is the first report of cancer following fetal
neural stem cell transplant.
However, outside experts raised concerns about the safety of the transplant
procedure used in this case, suggesting that other stem cell transplants
conducted with more oversight may not carry an increased risk.
The boy suffered from a recessive genetic disorder called ataxia
telangiectasia (AT), an incurable, neurodegenerative disease that has left
him wheelchair-bound. In 2002, when he was 9, his parents took him from
Israel to Moscow to undergo experimental stem cell therapy. A team of
researchers in Moscow injected multiple transplants of neural stem cells,
which were derived and purified from the brains of aborted fetuses.
Four years later, the boy was diagnosed with a very slow growing form of
cancer called glioneural neoplasm after coming to the Sheba Medical Center
outside Tel Aviv, Israel, complaining of headaches.
A team led by Gideon Rechavi, a
pediatric hematologist and oncologist at Sheba Medical Center, performed a
histological analysis on the tumor to determine its makeup. They found it
contained a hodgepodge of different cell types -- this is unlike most brain
tumors, which arise from a single cell type, he said. The different types
suggest that the tumor "originated from a stem cell that can differentiate
towards various directions," said Rechavi.
To rule out the possibility the tumor came from the boy's own cells, given
that AT weakens the immune system and can predispose patients to cancer, the
researchers tried to determine its source. The team found that the tumor
could not have arisen from the boy, because he is homozygous for the
mutation that causes AT, while the DNA from the tumor cells carried only the
normal allele.
"This paper does a very good job of showing that the cells that constituted
this tumor did not arise from the patient and [were] not genetically
identical to either of the parents, and clearly came from the donor tissue,"
said Arnold
Kriegstein, a researcher at the Eli and Edythe Broad Center of
Regenerative Medicine and Stem Cell Research at the University of
California, San Francisco.
The case study raises a number of questions. Because the patient's immune
system was impaired, it's not yet clear whether the increased risk of cancer
is specific to patients with suppressed immune systems, something particular
to the procedure done in Moscow, or a danger with neural stem cell
transplantation in general, said
Uri Tabori, a
pediatric hematologist and oncologist at the Hospital for Sick Children in
Toronto, Canada. "This is a case report," he said. "It has its role in
saying it can happen, but we don't know if it's common, if it's uncommon,"
he said.
"It's a cautionary tale for studies currently being done in the US and
elsewhere," said Kriegstein.
Since the patient developed the brain tumor four years after the initial
injections, researchers may need to monitor patients for a long time after a
treatment to evaluate safety, Kriegstein said.
However, it's premature to translate these findings to studies conducted in
the US, said
Aileen Anderson, a neuroscientist who studies stem cells at the
University of California, Irvine. The researchers who conducted the
transplant followed the protocol of a group that has published only one
other
paper in an international, peer-reviewed journal, and the cells used are
a mixture of glial cells, neurons, and progenitors -- "a sort of cell mush,"
she said. These are "completely uncharacterized populations, populations
that would never be accepted in the US or any first-world country," she
said.
Kriegstein agreed. "It's absolutely scary," that the group conducted the
transplant, he said.
Currently, a company called Stem Cells, Inc., is conducting a Phase I
clinical trial to evaluate the safety of fetal neural stem cell transplants
for treatment of Batten Disease, an invariably fatal neurodegenerative
disorder that affects young children
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