Scientific American, June 12, 2007
Can adult stem cells do it all? (con't)
Difficulties growing stem cells are not unheard of. "The culture
conditions needed to grow various kinds of stem cells can be very
tricky," down to the source of the water, says neural stem cell
biologist David Anderson of the California Institute of Technology in
Pasadena. But the longer a study goes unreplicated, despite
researchers' best efforts, the less sound a result seems.
Against that backdrop, the London-based magazine New Scientist
reported in February that data presented in Verfaillie's July Nature
paper appeared under a different label but was otherwise identical in
a second paper published in Experimental Hematology in August of
2002. The data referred to cell surface proteins that supposedly
defined the cells. That month, an expert panel convened by the
University of Minnesota deemed the data "significantly flawed"
and "potentially incorrect" for further inconsistencies in the data,
but did not accuse Verfaillie or anyone in her lab of deliberately
manipulating it.
The flawed data did not contradict the paper's main claim that the
injected cells have a potential similar to that of embryonic stem
cells, researchers say, because they could simply have had other cell
surface proteins not included in the data. Additional problems
cropped up in March, however, when New Scientist reported that a
single image had appeared three different times in data from
Verfaillie's lab—once referring to bone and once to cartilage in a
2001 Blood paper about human MAPCs, and once again to describe bone
cells in a 2006 patent application.
In January, shortly before the first data problems came to light,
Verfaillie's work had received a boost when her lab together with
Weissman's reported they had replicated a second finding from the
2002 Nature paper—that MAPCs could partially replace the destroyed
bone marrow (where red blood cells are manufactured) of mice, which
by itself is unusual because they did not come from blood-forming
stem cells, Weissman says. He adds, however, that if they work as
reported, MAPCs are still not very efficient: one adult blood-forming
stem cell replaced as much bone marrow as a million MAPCs.
"There's still a lot of skepticism about the paper, even though Irv
is on it," says Chien. Weissman says his lab has still not created
MAPCs. For the experiment with Verfaillie, who now heads stem cell
research at the Catholic University of Leuven in Belgium, one of his
current postdoctoral fellows, Scott Dylla, implanted the cells in
mice in Leuven and brought them to Stanford to be examined.
Experts hesitate to pass judgment on Verfaillie, whom they describe
as a careful researcher. Still, the fishy figures and lack of
replication have raised eyebrows. "It all smells really bad," says
stem cell biologist Sean Morrison of the University of Michigan at
Ann Arbor Center for Stem Cell Biology. The important question, he
says, is still whether the findings can be reproduced. "There's a
tendency now for people to really tee off on Catherine" prematurely,
he says. Verfaillie did not return phone calls or e-mails asking for
comment.
Although opponents of embryonic stem cell research latched onto
transdifferentiation and MAPCs, few scientists have ever proposed
adult stem cells as an alternative to embryonic ones, Morrison says.
Eva Mezey, a stem cell biologist at the National Institutes of Health
who published one of the transdifferentiation studies and stands by
the effect, notes that embryonic cells are naturally more versatile
than adult stem cells. "That's their job," she says.
Morrison says the transdifferentiation studies have left a black mark
on the field but represents only a subset of research. "There are
always people with a get-rich-quick mentality," Morrison says. "It's
an occupational hazard in any field where there's a possibility of
having your paper end up on the front page of the New York Times. …
The fact that this is a high profile field means that when people
make mistakes it gets more attention."
"Where all of this gets really risky," Caltech's Anderson adds, "is
when clinicians start to move forward with trials that are based on
experimental results that may not be solid."
Transdifferentiation studies spawned a number of clinical trials,
including several in which heart attack patients received an
injection of blood-forming stem cells in their hearts in hopes of
replacing dead cardiac muscle. The results came in last year and were
not encouraging: In two shorter trials, heart function improved by a
few percentage points or not at all, and one longer study found a
slight but temporary benefit.
Weissman says that most clinical studies of stem cells fail to meet
what he sees as key criteria: They should be based on clear, peer-
reviewed demonstrations of tissue regeneration, replicated by a large
number of independent groups that provide rapid, long-lasting
benefits.
Chien agrees that basic stem cell biology has not kept pace with
clinical studies, but he says there is a compelling need for new
treatments. "I can understand why people are motivated to try to do
something" by conducting trials, he says. "They're going to go on and
we will learn something from them," he notes, although he adds that
treatments currently in the clinic are unlikely to enter the
mainstream.
Stem cell researchers maintain that whatever the potential of adult
stem cells, embryonic research could help them achieve it. Last
December, for instance, Chien's group reported finding markers for
heart muscle stem cells by tracing their development from embryonic
tissue.
Similarly, the three research teams that last week reported turning
mouse skin cells into embryolike cells say they will have to study
embryonic cells to learn how to reprogram human cells in the same way
and to understand their potential.
http://www.sciam.com/article.cfm?articleid=20989EDD-E7F2-99DF-
3238A9B01D86E583&chanId=sa022
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