Especially note Eggan's comments re SCNT and ESCR:

Source: Harvard Medical School

 Neurons Created from Skin Cells of Elderly ALS Patients

STEM CELLS, NEURONS, INDUCED PLURIPOTENCY, ALS, AMYOTROPHIC LATERAL 
SCLEROSIS, LOU GEHRIG'S DISEASE
Less than 27 months after announcing that he had institutional permission to 
attempt the creation of patient and disease-specific stem cell lines, 
Harvard Stem Cell Institute (HSCI) Principal Faculty member Kevin Eggan 
today proclaimed the effort a success.

Newswise - Less than 27 months after announcing that he had institutional 
permission to attempt the creation of patient and disease-specific stem cell 
lines, Harvard Stem Cell Institute (HSCI) Principal Faculty member Kevin 
Eggan today proclaimed the effort a success - though politically imposed 
restrictions and scientific advances prompted him to use a different 
technique than originally planned.
The breakthrough by Eggan and colleagues at Harvard and Columbia University 
marks the first time scientists are known to have produced human stem cell 
lines coaxed from the cells of adult patients suffering from a 
genetically-based disease. The affected patients had Amyotrophic Lateral 
Sclerosis (ALS), commonly known as Lou Gehrig's disease.
The work, published in today's on-line edition of the journal Science, 
provides "proof of concept" for the belief of scientists and fervent hope of 
patients that in the not-too-distant future it may be possible to treat 
patients suffering from chronic diseases with stem cell-based treatments 
created from their own adult cells. However, Eggan believes that the first 
therapeutic use of these newly derived stem cells will in fact be to use 
them to study the root cause of this disease and to screen for drugs that 
may provide benefit in patients.
The co-lead authors of the Eggan paper are John Dimos, a postdoctoral fellow 
in Eggan's lab, and Kit Rodolfa, a graduate student in the lab. Dimos and 
Rodolfa were responsible for the generation of the stem cells as well as 
their characterization. The Columbia team, which coordinated patient 
participation and skin sample collection, was lead by Christopher Henderson, 
co-director of that university's Motor Neuron Center and professor of 
pathology and cell biology in neurology and neuroscience.
"This finding by Kevin Eggan and his colleagues marks an important step in 
fulfilling the promise of regenerative medicine," Harvard Provost and 
neurobiologist Steven E. Hyman said. "It is yet more confirmation that the 
substantial risks that were taken in forming the Harvard Stem Cell Institute 
will ultimately pay off for both science and patients," he said.
In the Science paper, the HSCI and Columbia researchers, who were supported 
by the New York Stem Cell Foundation and Project ALS, describe turning skin 
cells collected from elderly patients with (ALS) into induced pluripotent 
stem (iPS) cells, and then directing their differentiation into the type of 
motor neurons (nerve cells) destroyed by the disease.
"No one has ever managed to isolate these neurons from a patient and grow 
them in a dish," Eggan said, explaining the significance of the work. "Now 
we can make limitless supplies of the cells that die in this awful disease. 
This will allow us to study these neurons - and ALS - in a lab dish, and 
figure out what's happening in the disease process," said the assistant 
professor in Harvard's new Department of Stem Cell and Regenerative Biology, 
and Stowers Medical Institute Investigator.
When Eggan and colleagues first applied to Harvard and Columbia 
Institutional Review Boards (IRBs) for permission to attempt their 
experiments, they were planning to reach their goal through somatic cell 
nuclear transfer (SCNT), which is generally referred to as therapeutic 
cloning. Going the SCNT route requires obtaining donated ova, removing all 
the genetic material from the ova and replacing it with the genetic material 
from the skin cell of a patient whose disease researchers want to study. 
Stem cells would then be extracted from the fertilized ova after several 
cell divisions, and the idea would be to induce those stem cells to 
differentiate into the cell type to be studied.
"Over the last two years we've done everything we could within the law in 
Massachusetts to recruit women to donate ova. However, we were never able to 
recruit enough donors because we were legally prevented from providing the 
same sort of compensation that these women would receive for donating their 
ova for in vitro fertilization," Eggan said.
"We did make some interesting progress with initial experiments," he 
continued, "but it's not yet come to fruition. So when Shinya Yamanaka's 
first creation of iPS cells came along, that opened up a new route for us 
and we decided to capitalize on that." However, Eggan added that he will 
continue both his SCNT and iPS work, and believes "it's essential to note 
that we couldn't possibly be where we are now without first doing extensive 
work with human embryonic stem cells(hESC). Further, it will be essential to 
continue to do work with embryonic stem cells as they remain the stem cell 
gold standard."
The Eggan team used the same four genes to produce iPS cells that Yamanka, 
of Kyoto University, used to develop his reprogramming method in mice two 
years ago. However, because one of the four genes is a cancer-promoting 
gene, this method of reprogramming will for the time being prevent these 
cells from being transplanted into patients.
In order to perfect these cells for transplantation, scientists will have to 
come up with a combination of genes or chemicals to induce similar 
reprogramming events in the skin cells without the use of potentially 
tumor-causing agents.
The skin cells used in the experiment came from two Columbia patients, one 
89 and the other 92. Both patients had a mild form of ALS, but one that is 
caused by a single genetic mutation. The genetic simplicity of this form of 
ALS - and the fact that it always inherited - should assure that the neurons 
produced from these stem cell lines will eventually succumb to the disease.
At this point however, the Eggan group has not yet seen the disease in the 
dish. "The next step," said Eggan, "is to produce neurons from iPS cells 
developed from a normal, healthy person, and try to determine what's 
different about the neurons we have made from the ALS patients."
© 2008 Newswise.  All Rights Reserved.

Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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