[WE knew this since June - but here's Scientific American's point]
Korean Cloned Human Cells Were Product of "Virgin Birth"
Fraudulent cloned cells were likely the first example of a human egg
turned directly into stem cells
By JR Minkel
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Image: © KIM KYUNG-HOON/REUTERS/
ORIGIN OF KOREAN CLONED CELLS: Hoo Suk Hwang, the South Korean
researcher who fraudulently claimed to have created cells from cloned
human embryos, may in fact have stumbled onto the first stem cells
made directly from human eggs.
Researchers say they have confirmed suspicions that embryonic stem
cells claimed to be extracted from the first cloned human embryo by
discredited South Korean scientist Woo Suk Hwang actually owe their
existence to parthenogenesis, a process in which egg cells give rise
to embryos without being fertilized by sperm.
A series of genetic markers sprinkled throughout the cells'
chromosomes show the same pattern found in parthenogenetic mice as
opposed to cloned mice, according to a report published online today
in the journal Cell Stem Cell.
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The result suggests that, although Hwang deceived the world about
achieving the first human cloning, his group was first to succeed in
performing human parthenogenesis, which may offer a way of creating
cells that are genetically matched to a woman for transplantation
back into her body to treat degenerative diseases.
"I think this is an extremely important—and solid—paper," says stem
cell researcher Robert Lanza, vice president of research and
scientific development at Applied Cell Technology, a regenerative
medicine company headquartered in Alameda, Calif., who did not take
part in the study. "It conclusively proves that the stem cell line in
question was not cloned as claimed, but rather was generated through
parthenogenesis.
The result follows on the heels of an announcement last month by
another California stem cell company, International Stem Cell
Corporation (ISC) in Oceanside, that it had successfully achieved
human parthenogenesis for the first time. Last year, Italian
researchers claimed to have achieved the same feat but have yet to
publish their results.
"The fact that this has now been achieved by two independent groups
gives me a far greater degree of confidence," Lanza says.
The new finding brings a measure of closure to a story that first
rocked the science world in February 2004, when Hwang and colleagues
at Seoul National University announced they had cloned a female
donor's cell by transferring its nucleus into one of her egg cells
stripped of its nucleus in a procedure known as somatic cell nuclear
transfer (SCNT), and harvested embryonic stem cells from the
resulting fusion. They published the result the next month in
Science.
Image: REVAZOVA ET AL., 2007, CLONING AND STEM CELLS
FIRST (DELIBERATE) HUMAN PARTHENOTE: In late June, a California
company published the first report of cells derived from human eggs
stimulated to grow into embryos. The cells are shown here after
transplantation into a mouse.
The claim went up in smoke in January of 2006 after a probe by the
university concluded that Hwang had fabricated the evidence, which
followed a similarly damning assessment of a landmark paper from the
previous year in which the group falsely reported creating 11 cell
lines genetically matched to their donors.
Unsolved Mysteries
A cloned cell should be identical to its donor, but the probe found
that of 48 common genetic variations, or markers, present in the 2004
cells, eight did not match their apparent donor. Investigators raised
parthenogenesis as the most likely explanation but could not be
certain.
Later, during a chance discussion with European colleagues, stem cell
researcher George Daley of Children's Hospital Boston and the Harvard
Stem Cell Institute learned that they had received samples of the
cell line before the work was retracted. "We had read the suspicions
that the cell was a parthenote, but also realized that it had never
really been proven," Daley says.
To settle the case, they analyzed the genetic sequence of the cell
line at 500,000 locations across the genome.
The DNA of any two people will differ on average at one of every
1,000 subunits, or base pairs, Daley says. When a chromosome from a
sperm cell joins with that of an egg, these single nucleotide
polymorphisms (SNPs or "snips") tend not to match each other.
The same goes for cloned cells. But in contrast, pairs of matching
chromosomes in parthenogenetic cells tend to match one another in the
middle and differ near the ends because of a genetic mixing process
called recombination. In their paper, Daley and colleagues report
that the SNPs in the Korean cell line do indeed match toward the
center of the chromosomes, similar to five parthenogenetic mouse cell
lines that the team created for comparison.
In a separate analysis, they also found that three regions lacked the
chemical modifications, or imprinting, that paternal genes impose on
a fertilized embryo to prevent those genes from being activated.
Jeffrey Janus, president and director of research for ISC, agrees
that "Dr. Hwang's cells have characteristics found in parthenogenetic
cells" but remains cautious, saying "it needs more study."
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The Irony of It All
Stem cell experts say that Hwang and his team probably had no clue
what they had achieved, because if they had they would have claimed
credit for it.
"I think this … is every bit as exciting as the SCNT they were
claiming," says stem cell researcher Kent Vrana of Pennsylvania State
University, who pioneered parthenogenesis in monkeys. "Parthenotes by
their very nature are nonviable embryos, so you're not destroying
embryos, which has some ethical advantages."
Vrana says the Korean team used a procedure common in attempts to
induce parthenogenesis and SCNT alike, in which they injected egg
cells with calcium and a protein synthesis inhibitor to mimic what
happens when sperm fertilizes an egg.
To achieve SCNT, they first had to extract each egg's DNA and then
inject the donor cell nucleus. Daley says the Korean scientists must
have inadvertently left the DNA intact in one of the 242 egg cells
they injected. "They claimed they verified the removal of the DNA,''
Daley says, "but obviously they didn't."
The injection of the donor nucleus could have failed if the injecting
needle pulled it back out when withdrawn from the egg or if the egg
somehow rejected the introduced nucleus, Vrana says.
Hwang's group purported to rule out parthenogenesis as an explanation
in part by showing that two genes normally activated by paternal DNA
were inactive in the cells. But Daley says such experiments are easy
to misinterpret and are less conclusive than sequencing SNPs.
"I think they were just so blinded by what they hoped to accomplish,
they missed it," Vrana says.
As a result, in late June, more than a year after Science retracted
the 2004 paper, researchers at ISC were able to claim the discovery
of human parthenogenetic cell lines as their own in the journal
Cloning and Stem Cells. The group reported growing multiple
parthenogenetic embryonic stem cell lines by incubating eggs in a
warm, low-oxygen culture medium.
Before today's announcement, the work was already "awfully
convincing," Vrana says, and surprisingly successful: out of some 50
donated eggs, the company grew six cell lines. Parthenogenesis in
monkeys typically works only once every 90 eggs, he says.
Banking on Parthenotes
The therapeutic potential of parthenogenetic cells remains to be
seen. The lack of imprinting from the paternal DNA may cause the
cells to behave abnormally as they develop. Furthermore, they must
have matching immune proteins to be transplanted back into a donor.
In principle, tissue banks of parthenogenetic cell lines could
include enough different immune protein combinations to treat up to
half of the U.S. population—men as well as women—Lanza says. But he
adds that if human parthenotes routinely contain as many genetic
mismatches as the Korean cells, the number of eggs needed to create
such a bank could be prohibitively large.
Daley says his group hopes to acquire donated eggs from women with
inherited diseases and use parthenogenesis to create cell lines to
study those disorders. In the future, researchers will have to
determine whether similar cells are safe and effective when
transplanted.
"We're a long, long way," Daley says, "from realizing therapeutic
uses of these cells."
http://www.sciam.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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