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Her Own Umbilical Cord Blood Stem Cells Help Toddler with Cerebral Palsy

New Technique Produces Genetically Identical Stem Cells

NEW! Stem Cell Researchers Make ALS (Lou Gehrig's) Advances Without Destroying Human Embryos / iPS Cells from ALS Patient an Advance, But It's Not the First Patient-Specific Stem Cell

Pining for Clones, Whining for Eggs

CORD BLOOD STEM CELLS HELP TODDLER WITH CEREBRAL PALSY. Umbilical-cord blood has been used to treat 2-year-old Chloe Levine, who was born with cerebral palsy, a neurological disorder that prevented her from using the right side of her body.

Two months after the AZ toddler was infused with stem cells from her own umbilical-cord blood, Levine has made a 50 percent recovery and is walking, running and able to use her right hand. 

Dawn Vargo, bioethics analyst for Focus on the Family Action, said: “Chloe's recovery demonstrates that is it possible to treat children suffering from life-altering diseases without destroying young lives through destructive embryonic stem-cell research.”
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NEW TECHNIQUE PRODUCES GENETICALLY IDENTICAL STEM CELLS. Adult cells of mice that were made from iPS (induced Pluripotent Stem) genetically reprogrammed cells can be triggered via drug to enter an embryonic-stem-cell-like state, without the need for further genetic alteration.

The discovery is reported in Nature Biotechnology.

"This technical advancement will allow thousands of identical reprogrammed cells to be used in experiments," says Marius Wernig, one of the paper's two lead authors and a postdoctoral researcher in Whitehead Member Rudolf Jaenisch's lab.

"Using these cells could help define the milestones of how cells are reprogrammed and screen for drug-like molecules that replace the potentially cancer-causing viruses used for reprogramming," adds Christopher Lengner, the other lead author and also a postdoctoral researcher in the Jaenisch's lab.

In the current work, Wernig and Lengner made mice created in part from the embryonic-stem-cell-like cells known as IPS cells.

The IPS cells were created by reprogramming adult skin cells using lentiviruses to randomly insert four genes (Oct4, Sox2, c-Myc and Klf4) into the cells' DNA. The IPS cells also were modified to switch on these four genes when a drug trigger, doxycycline, is added to the cells.

Wernig and Lengner then took cells from each iPS mouse and introduced the doxycycline trigger, thereby changing the adult mouse cells into iPS cells.
While earlier reprogramming experiments have typically induced pluripotency in adult skin cells, Wernig and Lengner were able to employ this novel method to successfully reprogram multiple cell and tissue types, including cells of the intestine, brain, muscle, kidney, adrenal gland, and bone marrow.
Importantly, the technique allows researchers to create large numbers of genetically identical IPS cells, because all cells in the mouse contain the same number of viral integrations in the same location within the genome.

With previous approaches, each reprogrammed cell differed because the viruses used to insert the reprogramming genes could integrate anywhere in the cell's DNA with varying frequency.
Wernig and Lengner's method also increases the reprogramming efficiency from one in a thousand cells to one in twenty.
The large numbers of IPS cells that can be created by this method can aid experiments requiring millions of identical cells for reprogramming, such as large-scale chemical library screening assays.
"In experiments, the technique will eliminate many of the reprogramming process's unpredictable variables and simplify enormously the research on the reprogramming mechanism and the screening for virus replacements," says Jaenisch, who is also a professor of biology at Massachusetts Institute of Technology.
The research was supported by the Human Frontiers Science Organization Program, the Ellison Medical Foundation, the Ruth L. Kirschstein National Research Service Award, and the National Institutes of Health.

Journal reference:
   1. Marius Wernig, Christopher J Lengner, Jacob Hanna, Michael Lodato, Eveline Steine, Ruth Foreman, Judith Staerk, Styliani Markoulaki, and Rudolf Jaenisch. A novel drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nature Biotechnology, July 1, 2008
Adapted from materials provided by Whitehead Institute for Biomedical Research.
[ScienceDaily, July 6, 2008]




STEM CELL RESEARCHERS MAKE ALS ADVANCES WITHOUT DESTROYING HUMAN LIFE. Researchers at Harvard and Columbia have made advances dealing with ALS and stem cells without having to destroy human life. The scientists were able to use a new technique to transform the skin cells of patients with Lou Gehrig's disease into motor neurons.

The process may one day be able to create tailor-made cells to replace the damaged ones and either reverse or slow down the deadly disease.

An article on the research is scheduled for the July 31 edition of the medical journal Science describes the direct reprogramming process used to make the stem cells revert back to an embryonic-like state.

Study co-author Chris Henderson, a professor of pathology, neurology and neuroscience at Columbia talked with Science Daily about the news.

"Up until now, it's been impossible to get access to the neurons affected by ALS and, although everyone was excited by the potential of the new technology, it was uncertain that we would be able to obtain them from patients' skin cells," he said.

"Our paper now shows that we can generate hundreds of millions of motor neurons that are genetically identical to a patient's own neurons. This will be an immense help as we try to uncover the mechanisms behind this disease and screen for drugs that can prolong life," he said.

The motor neurons were created using a new technique that reprograms human adult skin cells into cells that resemble embryonic stem cells.

The technique used to make these cells – called induced pluri

potent stem (iPS) cells – was a major advance in the field that was first reported last November by researchers in Japan and Wisconsin.

Those studies used skin cells from healthy adults, but it remained unknown whether iPS cells could be created with cells from chronically-ill patients and then transformed into neurons

The Columbia-Harvard team, in this paper, showed this was possible using an ALS patient's skin cells.

Bioethicist Wesley Smith says the news is a victory for pro-life advocates who have pressed for ethical stem cell research that doesn't involve the destruction of human life in human cloning or embryonic stem cell science.

"One of benefits of human cloning, we were told, would be the ability to clone someone with a disease like ALS to obtain stem cells from the embryo for disease study," he said. "Indeed, before he decided to abandon cloning in favor of iPSCs, that is precisely what Ian Wilmut had a license to do in the UK."

"Well, so far no human cloned embryonic stem cells have been derived despite years of trying," he explained.

"But in less than one year since the first iPSC human line was created, that precise achievement has already been accomplished."

Smith said the news is an amazing achievement that comes because of President Bush's courage not to force taxpayers to fund embryonic stem cell research. That has allowed ethical alternatives to flourish.

"Think of it: no women's health endangered from egg extraction, no instrumentalization of human life, few brave new world worries. A true win-win," Smith concluded. [1 August 2008, Ertelt,, Boston, MA]

iPS CELLS FROM ALS PATIENT AN ADVANCE, BUT NOT THE FIRST PATIENT-SPECIFIC STEM CELL. A team of scientists from Harvard University and Columbia University has reprogrammed skin cells from two elderly patients with ALS (Lou Gehrig's disease), producing iPS cells, an embryonic-type (but ethical) stem cell.

Then from the iPS cells, they produced cells resembling motor neurons, the type of neurons that are attacked in the disease.

This is the first time any embryonic-like stem cell has been created directly from a patient.

The iPS cell technology, developed by Dr. Shinya Yamanaka of Japan, directly reprograms normal cells such as skin cells into an embryonic stem cell type, using the addition of 3-4 genes.

No embryos, eggs, or cloning are used in the process.

Yamanaka first developed the technique in mice, then transferred the same process to use with human cells. The first human iPS cells were announced in November 2007 by Yamanaka and by Dr. James Thomson.

In the few months since then over 100 human iPS cell lines have been created by various labs, but this is the first published instance where iPS cells were created from a patient with a specific disease.

Further work will be needed to show whether the immature neurons that were produced can mature to functional motor neurons in the lab dish, whether they are similar to the motor neurons in ALS patients, and if they can provide any clues to the development of the disease. The team hopes that they can use the iPS-derived neurons to study the disease in the lab.

The Harvard team, led by Kevin Eggan, had been attempting to create patient-specific stem cells for over two years, by trying to produce embryonic stem cells from human embryos by cloning (somatic cell nuclear transfer, SCNT) but had failed, in part because of the scarcity of human eggs (see Pining for Clones, Whining for Eggs) as well as the tremendous inefficiency of the cloning process.

One of Eggan's co-authors, Christopher Henderson, noted that if the iPS technique holds its promise in producing neurons and other cells for research, it will probably replace the cloning approach.

Dr. Rudolph Jaenisch of MIT, another cloning scientist, noted that the iPS cell technology "is so much easier, [with] so many fewer restrictions and problems – ethical as well as others." Jaenisch's lab had also tried the cloning concept in mice and failed, but succeeded with the iPS cells. These same reasons led Prof. Ian Wilmut, cloner of Dolly the sheep, to give up on cloning in favor of Yamanaka's technique.

The results of this study should put another nail in cloning's coffin.

Eggan still insists that he will continue with cloning research, but all the results are flowing from iPS cells.

The New York Stem Cell Foundation, previously a die-hard supporter of cloning and very critical of iPS cells, wasted no time in trumpeting their "critical funding role" in the new study. One of Eggan's major funders, the Stowers Institute, has relentlessly pushed cloning. Stowers poured $30 million into Missouri in 2006 to pass Amendment 2, a state constitutional amendment to secure the right to create cloned human embryos. Stowers CEO, William Neaves, has said that "the ultimate goal is not to create therapies with somatic cell nuclear transfer" but also that "The ultimate goal of all lines of this research is to be able, eventually, to reprogram ordinary body cells so that they could be used for therapy to replace cells that have been destroyed by injury or disease." Sounds like iPS cells are achieving that goal.

One company that rejected the iPS technique is Advanced Cell Technology (ACT). William Caldwell, CEO, had said in January 2008 that iPS "is not a substitute for what we're doing now." ACT was recently reported on the verge of bankruptcy. Similarly, Thomas Okarma, CEO of Geron, ignoring the facts and statements of the scientists, said that the iPS technique was "too complicated and too expensive." (Maybe he should look at what happened to ACT.) Cloning continues to fail, iPS cells keep delivering results.

Back to some inaccuracies in most of the news reports on this latest study. What they did was show for the first time that iPS cells, an embryonic stem cell, could be made directly from patients with a disease (without harming the cell donor, and without using eggs, embryos, or cloning), and also that they could produce in the lab a specialized cell type similar to that affected in the disease.

But is this the first instance of a disease-specific human cell line?

No, there are lots of those, going all the way back to 1952 and the very first cultured human cell line, the HeLa cell line (the disease in that instance was cancer.)

But isn't this the first instance of a patient-specific stem cell line?

No. That honor belongs to the Australian group led by Professor Alan Mackay-Sim of Griffith Uni

versity, that already made patient-specific and disease-specific stem cell lines. They isolated adult stem cells from the nasal tissue of patients, including Parkinson's patients. AND they turned those stem cell lines into the type of tissue affected in the patient,. AND they have already gone beyond the iPS result; they used their adult stem cell lines in an animal model of Parkinson's disease. AND the adult stem cells successfully treated the disease in the animals. Without tumor formation.

So the current iPS cell result is a nice advance, but it's not the first evidence of patient-specific or disease-specific stem cells, and certainly not the best.

Posted by David Prentice on August 2, 2008
iPS Cells from ALS Patient an Advance, But Not the First Patient-Specific Stem Cells 




Would-be cloners continue to complain that they cannot get enough human eggs for their experiments to create human clones. AP reporter Marcus Wohlsen reports that scientists and biotech entrepreneurs are pushing for payments to women who donate eggs for research.

The push has been especially strong in California and Massachusetts, where payments to egg donors for research are prohibited, and where several research groups continue to push for human clones.

Wohlsen accurately lays out the experimental science as well as the controversy. As the article notes, "The conflict centers on an effort to create stem cells from embryos that are exact clones of adults."

Cloning (technically termed somatic cell nuclear transfer, SCNT) involves transferring the nucleus of a body cell such as a skin cell (a "somatic" cell) into an egg that has had its own nucleus/chromosomes removed. The result is creation of an embryo.

But one of the problems with cloning is that it is a famously inefficient technique.

This means that a huge number of eggs are required to create just a few embryos. Hence the problem with human cloning–where to get all of the human eggs?

As Wohlsen notes, "One of the problems is that there is a significant risk to the health of a woman who donates eggs."

High doses of hormones are used to "hyperstimulate" a woman's ovaries, to produce not 1 or 2, but 10, 20, or 30 eggs at a time. And the hyperstimulation can lead to serious consequences for the women.

As Wohlsen says, "Even under normal doses, drugs used to coax eggs for use by fertilization clinics can occasionally lead to serious complications caused by excessive stimulation of the ovaries. In rare instances, the condition can be fatal."

Stanford professors Magnus and Cho give these figures:

"Between 0.3 and 5% or up to 10% of women who undergo ovarian stimulation to procure oocytes experience severe ovarian hyperstimulation syndrome, which can cause pain, and occasionally leads to hospitalization, renal failure, potential future infertility, and even death."

For a sample of what can go wrong, see the story of Calla Papademas; for more info see the website of Hands Off Our Ovaries, a feminist group opposed to risking women's health for risky experiments.

In their June 2005 article in Science, Magnus and Cho also address the hype associated with cloning and potential cures, what they term the "therapeutic misconception":

"…researchers must make every effort to communicate to these volunteers that it is extremely unlikely that their contributions will directly benefit themselves or their loved ones. Also, it is nearly certain that the clinical benefits of the research are years or maybe decades away. This is a message that desperate families and patients will not want to hear."

Perhaps coincidentally, the Magnus and Cho article appeared in the same issue of Science as one of the fraudulent human cloning papers of Woo-Suk Hwang, where he claimed he had cloned patients to create "patient-specific embryonic stem cells".

Still the whining continues that many more eggs are needed for cloning.

Kevin Eggan at Harvard has complained loudly that two years and $100,000 in advertising brought in a total of only one egg donor. Cloning proponents also claim that the lack of eggs is "preventing medical breakthroughs". One of their claims is that cloning will create embryonic stem cells that will match the patient who has been cloned, the so-called "patient-specific stem cells".

Actually two simpler, more straightforward, and cheaper ways to get patient-specific stem cells have already been proven. Interestingly, one result was just announced by… Kevin Eggan of Harvard, making induced pluripotent stem (iPS) cells from the skin of patients with ALS (Lou Gehrig's disease).

The other way has been published by an Australian team, using nasal adult stem cells from patients.

One might wonder, then, why the continued angst about getting eggs and human cloning.

One answer may be economic. The only team to publish verified cloning of a human embryo is the company Stemagen, in January 2008. No stem cells were obtained at all, but they are supposedly continuing to try cloning in the hopes that they can market the cells from cloned embryos, or maybe the embryos themselves.

Part of their success apparently resulted from getting fresh human eggs direct from the fertility clinic. Conveniently, one of the Stemagen cloners, Wood, runs the Reproductive Sciences Center in San Diego, the in-vitro fertilization clinic that obtains the eggs.

This brings up the question of conflict of interest for those harvesting the eggs, torn between caring for the health of the women donating eggs vs. the incentive to retrieve as many eggs as possible.

According to a recent story, more women are donating eggs to fertility clinics, but often to help their financial situation.

Supporters of restrictions on payments for egg harvesting for research note that the restrictions are necessary to avoid creating a market for human eggs that encourages women to risk their health for speculative science.

Whether the push for egg payments in California is related to creating a market for eggs to allow cloning, and relationships between Stemagen and Alan Trounson, the President of California's stem cell quango, was recently examined by the California Stem Cell Report. Questions about Trounson have surfaced before, especially in relation to his attempted rat-trick with Australian MP's during their embryo research debate in 2002.

Given the easier, cheaper, and much more successful alternatives, and the significant ethical problems related to getting human eggs, it would seem the idea of SCNT cloning should be q

uickly dropped.

Posted by David Prentice on August 2, 2008