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More than a year ago, President Bush restricted all federally funded scientists to use 78 existing stem-cell lines for their research.

Bush: Leading scientists tell me research on these 60 lines has great promise that could lead to breakthrough therapies and cures.  This allows us to explore the promise and potential of stem cell research without crossing a fundamental moral line..."

Sen. Sam Brownback, R-Kan., is one who supports tough restrictions on stem-cell use. A bill sponsored by Brownback would criminalize the use of any embryonic stem cells or stem cell-derived therapies obtained through human cloning.

"New advances in adult stem-cell research, being reported almost weekly, show more promise than destructive embryo research," Brownback said during a speech on the Senate floor last year.

Bush: "Even the most noble ends do not justify the means."

Some scientists suggested the success might someday make it unnecessary to pursue "therapeutic cloning," in which cloned embryos would be created as a source of therapeutic tissues that match the genetic signature of the patient.

The cells "are pretty rare ... but they can be expanded very easily," he said. The technique is "very simple," and many laboratories will be able to use it and move this field forward, he said.

Adding various growth factors, Huberman's group was able to get the monocyte stem cells to express markers that indicated they had become brain cells, liver cells and skin cells. They also succeeded in getting the stem cells to transform into cells of the immune system and cells lining blood vessels, he said.

In addition, the monocyte cells can be frozen and still retain their vitality. This indicates the cells could be obtained from frozen blood and used to treat patients. "If an individual donates blood, we can freeze it and later isolate these stem cells and hopefully use it in the future to help people," he said.

Optical fractionation is based on holographic optical tweezers technology. HOT technology uses forces exerted by strongly focused, computer-generated holograms to create very large arrays of discrete optical traps. Each trap is capable of suspending a microscopic object motionless in three dimensions.

"It's a new approach based on very old principles," Grier said. "If you've seen the tiles on a Spanish roof that direct rainwater, in some respects this operates on the same principle."

The potential applications of optical fractionation include routine medical testing, pharmaceutical research and the development of entirely new biotechnological markets.

Optical fractionation is complementary to and more flexible than existing techniques such as gel electrophoresis, Grier said. Almost all of the existing techniques involve a competition between two forces that act in opposite directions along the same axis. In the case of gel electrophoresis, an applied electric field drives objects such as DNA in one direction, while the viscous drag of the gel opposes that motion.

One also can adjust the laser wavelength and power and the trap geometry, allowing the traps to instantly sort objects ranging in size from less than 100 nanometers (the size of the Human Immunodeficiency Virus), to near 100 micrometers (the diameter of a human hair).

"Scientifically, using a variety of human cells to support the growth of human embryonic stem cells could speed the hunt for the signals that keep the primitive cells from changing. If that happens, we might not need any feeder cells at all."

"When it is time to create new stem cell lines, this issue will be very important," says Cheng. "Our results together with others' show that it should be possible to establish new stem cell lines without using mouse cells or proteins."

scientists in Singapore reported using human cells -- one set from fetuses, one from the reproductive tract of women -- as feeder cells to grow human ES cells in the lab. But the cells from adult bone marrow have some distinct advantages, says Cheng.

Only 9 lines are able to be cultivated and 62 still won't culture. These mainly dysfunctional lines are the "Bush approved stem cells"

Texas House Bill 1175, by Rep. Phil King, R-Weatherford, would ban engaging or attempting to engage in human cloning and would restrict stem cell research.

A human embryo is defined in the bill as a living organism with a full or nearly full human genetic composition in the earliest stages of development, including the one-cell stage.

Violators of the proposed ban would be subject to civil penalties up to $10 million and felony charges carrying a maximum penalty of life in prison.

A British-led team of doctors has taken a revolutionary approach to this delivery problem and, they say, given convincing evidence of GDNF’s promise.
“It turns out that apart from some fiddling with the concentration of the GDNF, the patients tolerated it very well and started to show effects of getting better within two to three months. The improvement came very fast.” After a year, the five recruits showed on average a 39-percent improvement in motor skills, and a 61-percent improvement in their quality of life. Scans showed that the targeted cells had a 28 percent increase in dopamine storage. In addition, jerky movements caused as a side-effect of taking L-dopa fell massively, by nearly two thirds.

Israeli's ES Cell International moves to Singapore

Sources of cells are excess embryos from fertility clinics. The American Society for Assisted Reproductive Technology reported Thursday that there are 396,526 frozen embryos in storage in the United States and that 88 percent are planned for use in helping families have children in the future.

The finding that only 11 cell lines are currently available instead of more than 70 led to a call for lifting the restrictions and development of new cell lines.

That changed in 2002, when New Scientist revealed that Catherine Verfaillie of the University of Minnesota had discovered "multipotent adult progenitor cells", or MAPCs, apparently capable of giving rise to all tissues in the body, just like embryonic stem cells (26 January 2002, p 4). The work was later published in Nature.

The legal repercussions of Genzyme's claims could also be profound. Osiris already has several patents on MSCs and some of their medical applications, while Verfaillie has a pending patent application on MAPCs. What if they are the same cell?  "Only one [group] can get a valid patent to the thing itself," says British patent attorney Andrew Sheard. "If it really is the same thing it doesn't sound hopeful for the second group."

Genzyme started looking at the potential of stem cells from different labs. 
"People weren't using the same set of tools to evaluate their cells," says Tubo.
His team therefore set out to devise a systematic way of comparing different types of adult stem cells.

Out of many molecules that induced neuronal differentiation, the researchers focused on TWS119, which has the ability to bind a cellular kinase enzyme called glycogen synthase kinase-3beta, a multifunctioning "signaling" enzyme that modulates other enzymes by attaching a phosphate group to them.

Gene Found for Embryonic Stem Cell Potency::: Two research teams, one led by Austin Smith from the University of Edinburgh and the other led by Shinya Yamanaka of Japan's Nara Institute of Science and Technology, discovered the gene last year and have collaborated since.

In one experiment, for example, Smith's team inserted the human nanog gene into mouse embryonic stem cells and found that it prevented the cells from differentiating into specific types of tissue.

Researchers still have to determine, however, what signal turns nanog on, after which they may be able to develop drugs that activate the gene.

This will require more research on human embryos, which means that the controversy over their use won't go away soon.

"No wonder that only two of every five doctors still belong to the AMA, which in the 1960's used to speak for nearly nine of every ten doctors. With such an increasingly small minority, the AMA obviously no longer speaks for American doctors. And as its recent decision to advocate human embryo-destroying cloning proves, it does not speak for many within its dwindling membership, either."

"We're talking about an organization that actually advocates creating human life for the sole purpose of destroying it through highly speculative, questionable and unethical research. Why not instead devote your resources to promoting ethical adult stem cell research, which is curing real patients without destroying human life?"

Goldrich said the AMA guidelines "will be helpful for those physicians already doing [stem cell] research," as well as those who have thus far only contemplated it. "There may be some physicians who sat on the sidelines awaiting some sort of guidelines from their professional organization," he said.

Under the guidelines, physicians are free to decide whether to participate in stem cell research or to use products that result from this type of research. This allows physicians uncomfortable with the process the freedom not to participate, Goldrich said

According to a statement released by Emrick's doctors, Emrick died because of "an acute ischemic event (heart attack) most likely related to his underlying atherosclerotic disease process and repeated cardiac bypass surgeries."

South Korean researchers said yesterday they had succeeded in developing human embryonic stem cells in the bodies of mice.
Scientists from the institute injected human embryonic stem cells, carrying enhanced green fluorescent proteins (EGFP), into mice embryos. They then transplanted the embryos into the wombs of four mice. They said they succeeded in producing 11 healthy baby mice.
Of the 11 transgenic mice, five had stem-cells bearing EGFP genes in their hearts, livers, kidneys and cartilage. All progeny of the five also had the stem-cell genes.  They are perfect mice except for a few human genes, said Maria's head of research Park Se-Pill.

Canadian scientists have discovered that stem cells can trigger regeneration of severely damaged organs in animals, a feat that suggests it may be possible to trick the human body into healing itself.

The scientists injected bone marrow stem cells into diabetic mice, which were cured or back to normal within seven to 14 days. But the "most amazing" finding, said Dr. Bhatia, is that the stem cells triggered the rodents' damaged pancreases to regenerate on their own.

MPCs expressing thymidine kinase were able to exert a bystander killing effect on the cancer cell line SKOV3ip1 in vitro. In addition, we found that MPCs were able to support Ad replication, and thus can be used as cell vectors to deliver oncolytic viruses. Our results show that MPCs can foster expression of suicide genes or support replication of adenoviruses as potential anticancer therapeutic payloads. These findings are consistent with the concept that MPCs possess key properties that ensure their employment as cellular vehicles and can be used to deliver either therapeutic genes or viruses to tumor sites.

Bryan hopes the stem cell transplant will control the disease and put Bryan into remission.

All 10 patients who have received the transplant no longer suffer from any symptoms related to the disease, said Dr. Richard Burt, a stem cell transplant specialist and chief of the division of immunotherapy at Northwestern.

"We offer the stem cell transplant to those who have very serious disease and have failed everything else,"Burt said."The 10 we have done are all doing great and are in clinical remission."

The stem cell transplant procedure is still considered experimental, but it was approved by the Food and Drug Administration for clinical trials two years ago.

Bryan was scheduled to receive the transplant Sept. 15, but his father, a local police officer, has yet to come up with the $100,000 needed for the transplant, living expenses in Chicago and follow-up medical care.

Insurance won't cover the medical costs, because the transplant is considered experimental.

"The discovery of a cancer stem cell for brain tumours means that only a small number of cells in a brain tumour have the ability to drive tumour growth. Many current cancer therapies may fail because they do not kill the cancer-sustaining stem cells. We now have to work on designing therapies that will attack these stem cells," said Dr. Peter Dirks, an HSC neurosurgeon and scientist-track investigator in the Developmental Biology Research Program, and an assistant professor of Neurosurgery at U of T.

Lately the news magazines (and Congress) are abuzz about hopeful new cures to be found through cloning stem cells from human embryos. Yet "cloning for cures" is a smack in the face of God's creative authority. It's creating human life for the purpose of lethal experimentation and exploitation. A society that views life as a commodity grows calloused toward anyone weak and frail. Every medical condition researchers are using cloning to address already is being addressed more safely, effectively, and economically using adult stem cells. It's my prayer women will stand courageously on the side of life's sanctity through adult stem-cell research. God gave us life; safeguard it for the sake of your disabled children, husband, and elderly parents.

Sources of cells are excess embryos from fertility clinics. The American Society for Assisted Reproductive Technology reported Thursday that there are 396,526 frozen embryos in storage in the United States and that 88 percent are planned for use in helping families have children in the future. http://imminst.org/forum/index.php?s=&act=ST&f=44&t=873&st=40#entry9489

At the moment, the research depends on spare embryos left over from fertility treatment, but these are often of poor quality as the best ones have been selected to create babies.
http://imminst.org/forum/index.php?s=&act=ST&f=44&t=873&st=100#entry14306

We have derived four ES cell lines on mouse embryonic fibroblast cells in medium supplemented with basic fibroblast growth factor, human recombinant leukemia inhibitory factor, and fetal bovine serum. The source of these cell lines was poor-quality embryos that in the course of routine clinical practice would have been discarded. After continuous proliferation in vitro for more than 12 months, these ES cell lines maintained their developmental potential to form trophoblast and somatic cells, including cardiac muscle and neuronal tissue. http://stemcells.alphamedpress.org/cgi/content/short/21/5/521

A group of some 40 nations, led by Costa Rica and the United States and assembled with the help of U.S.-based anti-abortion groups, insisted on a treaty banning both the cloning of humans and "therapeutic" or "experimental" cloning, in which human embryos are cloned for medical research aims.

But Ann Corkery, representing the United States, argued a treaty allowing experimental cloning "would essentially authorize the creation of a human embryo for the purpose of killing it to extract stem cells, thus elevating the value of research and experimentation above that of a human life."

Oct 14 (Reuters Health) - After a heart attack, infusing stem cells into the coronary arteries that supply blood to the heart muscle leads to a reduction in the area of heart damage. Moreover, heart function improves after the treatment, German physicians report.

Stem cells are early-stage cells that can go on to become several different types of tissue. Dr. Stefanie Dimmeler and associates at J. W. Goethe-University Frankfurt isolated stem cells from the bone marrow or blood of 28 heart attack patients and about four days later infused the cells into the coronary artery that caused the heart attack.

OTTAWA (CP) — If pro-life MPs kill the government's bill on stem-cell research they will clear the way for such research to proceed in unregulated and potentially unethical fashion, scientists say.

The bill's demise would leave a wide-open field for human stem-cell research in the private sector, said Ron Worton, vice-president of research at the Ottawa Hospital.

It won't make any difference to ethical researchers since the work will proceed in any case, Worton in said an interview today.

"The sad thing is that if the legislation fails, they (legislators) don't put in the checks and balances that I think really are necessary, like cloning human beings, for example."

It would be an ironic outcome for the social conservatives who have fought the legislation because of ethical concerns, says Worton, and scientific adviser to the Stem Cell Network.

He sees little likelihood that the bill will pass, even though Health Minister Anne McLellan and House Leader Don Boudria insist it is a priority.

"I think everyone recognizes now this legislation has been on the books for quite a long time, they've had ample opportunity to pass it if they were going to."

Under the Assisted Human Reproduction Act, "therapeutic" cloning — cloning of human embryos for research purposes, also referred to as nuclear cell transfer — would be banned.

Researchers would only be allowed to use surplus embryos produced in the course of infertility treatment — embryos which would otherwise be treated as medical waste.

The Canadian Institutes for Health Research, a federal agency, has its own guidelines that ban therapeutic cloning, but they are only binding on the work that the agency funds. Those guidelines can also be revised without Parliamentary debate.

Many researchers believe the door for therapeutic cloning, already allowed in Britain, should be left open.

"We need to have a flexible, forward-looking regulatory system," says Michael Rudnicki, director of the nuclear medicine program at the Ottawa Health Research Institute.

"Making specific experiments illegal is antithetical to our whole western civilization, frankly, and is unprecedented in Western democracies."

Rudnicki believes most Canadian see therapeutic cloning as akin to organ donation.

"These embryos will be used to make embryonic stem cells which potentially will have therapeutic use down the road.

"Personally I think that making Dolly-the-sheep type cloning illegal to produce humans is something that most Canadians would agree with.

"I think the provision about making nuclear transfer technology, so-called therapeutic cloning illegal, is not wise."

The CIHR has delayed funding for embryonic stem-cell research while the bill is under debate, but it's expected to start approving projects if the bill fails.

A CIHR spokeswoman said a committee is being set up to make recommendations on funding.

Oct. 15, 2003. 08:20 PM

Dr. Jean Marie Stassen Presents Data at International Stem Cell Conference

DUBLIN, Ireland, Oct. 16 /PRNewswire/ -- ThromboGenics Ltd. is pleased to announce that Dr. Jean Marie Stassen, Head of R&D and a leading European researcher in pre-clinical cardiovascular therapeutics, presented "An Improved Medium for Stem Cell Culture" at the Stem Cells Regenerative Medicine conference in Princeton, NJ, USA on October 15, 2003.
Dr. Stassen spoke about a new embryonic stem (ES) cell culture medium developed by Thromb-X, NV (www.thromb-x.com), the R&D subsidiary of ThromboGenics, in Leuven, Belgium. The proprietary ES cell culture medium (called TX-WES), conditioned by a fibroblast cell line, allows derivation and maintenance of ES cell lines from all inbred mouse strains tested, including strains that were presumed to be non-permissive for ES cell derivation. The research expands upon results cited recently in the journal Stem Cells, in which the ES cell culture medium was used for expanding murine cell populations.

"The advanced technology used in this stem cell platform has been applied by ThromboGenics to identify three novel compounds now in various stages of therapeutic development -- microplasmin, placental growth factor (PlGF) and anti-Gas6," explained Dr. Stassen, who is based at the University of Leuven's Centre for Molecular and Vascular Biology. "Thromb-X has taken measures to make this technology available to other researchers for use in drug discovery."

STANFORD, Calif. ­ Bone marrow cells can fuse with specialized brain cells, possibly bolstering the brain cells or repairing damage, according to research from the Stanford University School of Medicine. This finding helps resolve an ongoing debate: Do adult stem cells transform from bone marrow cells into other cell types, such as brain, muscle or liver cells, or do they fuse with those cells to form a single entity with two nuclei? The research shows that for complex brain cells called Purkinje cells, fusion is the normal pathway.

Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor of Pharmacology, had previously shown that transplanted bone marrow cells can wind their way up to the brain in humans where they take on characteristics of Purkinje cells – large cells in the part of the brain that controls muscular movement and balance. She had also shown that mature cells in a lab dish can fuse with other cell types and take on characteristics of those cells.

In her most recent work, published in the Oct. 16 advance online issue of Nature Cell Biology, Blau showed that the bone marrow cells in mice fuse with existing Purkinje cells and activate genes normally made in Purkinje cell nuclei. The work will also be published in the November issue of the journal.

“I think that fusion might be a really important biological mechanism,” Blau said. She said researchers previously considered fusion to be less medically important than the idea that bone marrow cells may be able to change fates entirely. Blau disagrees with that assessment. “Fusion might be a sophisticated mechanism for rescuing complex damaged cells,” she said.

Blau and senior research scientist James Weimann, PhD, transplanted mice with bone marrow cells that had been genetically altered to produce a fluorescent green protein. Over the course of the next 18 months (75 percent of a mouse’s life span), they looked for signs of fluorescent green cells in the animals’ brains.

Over time, the group found an increasing number of Purkinje cells that glowed green under a microscope. Looking closely at these cells, they found two nuclei – one from the original Purkinje cell and one from the fused bone marrow cell. They also found that the compact nucleus of the bone marrow cell expanded over time to take on the appearance of the more loosely packed Purkinje cell nucleus.

The bone marrow nucleus in the fused cell also acts like a Purkinje cell nucleus, they found. When the group transplanted mice with bone marrow cells that only glow green when Purkinje cell genes are active, they found normal-looking Purkinje cells that glowed green. This showed that the bone marrow cells had fused with Purkinje cells and activated Purkinje cell genes.

Blau said the next step is to learn under what circumstances bone marrow cells fuse with Purkinje cells. “If you know what those signals are, you could deliver the signal to damaged tissue and recruit the body’s own bone marrow cells to treat disease.” Blau hopes these recruited bone marrow cells may be a way of repairing damage caused by injury, stroke or such illnesses Parkinson’s disease.

Other Stanford researchers who participated in the study include postdoctoral scholar Clas Johansson, PhD, and research associate Angelica Trejo.

Two research teams at UCSF and Stanford have discovered evidence that stem cells from adult bone marrow do not create a wide variety of cells in the body the way cells from embryos do -- a finding that could add fresh controversy to scientific and political battles over the issue.

The adult bone marrow cells appear to fuse with existing cells of the heart, liver and brain rather than differentiating into entirely new ones, the scientists said. The studies suggest that only embryonic cells have the potential to regenerate diseased tissues.

However, in the case of brain cells, the fusion may itself provide new paths to therapies for brain disorders, according to the Stanford scientists.

The findings were just published on the Internet -- one from UCSF in the advance online edition of the British scientific journal Nature, and the other from Stanford in the online edition of the related journal Nature Cell Biology. The two journals will carry the reports separately in future printed editions.

In both studies, the experimenters have been working with bone marrow from adult mice rather than embryos in order to learn whether -- as some scientists have claimed -- the adult marrow cells could differentiate into a wide variety of new cells that might be harvested to replace the damaged or destroyed cells that mark many diseases.

Instead of differentiating, however, the researchers found that the adult marrow cells fused with existing cells of the heart, liver and brain. Each fused cell contained two curiously distinct nuclei -- one from the original bone marrow cell and one from the cell with which the marrow cell had fused.

Whether such fused cells might eventually prove useful in therapy is a question both research teams hope can be answered in further research.

The Stanford team is headed by Helen M. Blau, director of the university's Baxter Laboratory of Molecular Pharmacology, while the leading author of the other report is Arturo Alvarez-Buylla, a professor of neurosurgery at UCSF.

Stem cells taken from embryos have been shown in many experiments to be capable of differentiating into virtually all cells of the body. Many scientists are highly optimistic that with more research, these stem cells will be able to replace damaged or nonfunctioning cells and thereby fight a broad variety of diseases.

But politically conservative members of Congress and the Bush administration have strongly opposed the use of newly created embryonic stem cells on the ground that exploiting the tissue of embryos would be highly immoral.

Theory not supported

A few scientists supporting that view have held that adult stem cells might prove at least as versatile, and suggested that research should focus primarily on their use while research using embryonic cells should be banned completely. But the Stanford and UCSF studies raise new questions about the usefulness of stem cells from adult bone marrow.

Still, Sean J. Morrison of the University of Michigan, who was one of Alvarez-Buylla's collaborators in the UCSF work, said that the newly- discovered phenomenon of cell fusion might be exploited for certain therapies.

"My hunch is that fusion might be a mechanism that the body has devised to import DNA from blood cells into damaged cells in various tissues,'' Alvarez-Buylla said. "This is an area we should be investigating thoroughly."

He and his colleagues cautioned, however, that clinical trials to study whether implanting bone marrow cells derived from adults could be used to replenish damaged cells in patients with diseases of the heart, liver or brain should be postponed until more research clears up the question.

Cells don't divide

Blau's team at Stanford looked specifically at the way adult bone marrow cells fused with cells in the brain known as Purkinje neurons. The fused cells do not divide, and thus cannot cause cancer. In addition, genes are activated in the fused cells that could endow them with therapeutic uses.

"Fusion can provide rescue from death and lead to tissue regeneration,'' Blau said. "Different stem cells are likely to have different advantages for different purposes. I like following the biology and keeping an open mind to what nature has to tell us.

"We need to study all types of stem cells. We know too little about each. And it seems likely that for different diseases one type may be more suitable than another. We can't predict at this point what will be therapeutically optimal and for what diseases.''

But in a recent experiment in South Korea, geneticists say they have added human embryonic cells — stem cells, with the ability to turn into brain, sperm or any type of cell — into the embryos of mice. That's unethical; down that road lies a chimera. In Greek mythology, that was the name of a fire-breathing monster combining lion, goat and snake; the name was adopted by modern scientists to mean "an organism with two or more genetically different types of cells."

Do we really want to cross a man with a mouse? Are we comfortable endowing a fellow primate like a chimpanzee with uniquely human characteristics — and all the half-human rights that would entail — in the name of medical research?

Today's longheaded thoughts are occasioned by the release of a rarity: a profound and readable report produced by a government committee. "Beyond Therapy: Biotechnology and the Pursuit of Happiness," by the President's Council on Bioethics, is at www.bioethics.gov. It poses the big questions fairly and lays out the data for futuristic debate. Because it runs over 300 pages, you might want to download the 24-page introduction by Dr. Leon Kass, the council chairman, and wait for some alert publisher to rush the report out in paperback.

In The Times's special issue at the turn of the millennium, I facetiously headlined an optimistic column about increased life expectancy "Why Die?" The council reports evidence suggesting that "a unified process of senescence does indeed exist" and that it may well be possible for biotechnology to achieve "age retardation," redoubling the past century's doubling of life span — but with lively old minds and healthy old bodies.

"It is a fact that research is going on on embryos in this country and has been explicitly permitted since 1987," said Baylis, who is about to publish a study on the availability of surplus embryos for research in Canada.

She said any high-quality fertility clinic that is seeking to improve success rates will train staff and conduct research using surplus embryos.

"If you're a person who's . . . having to manipulate a human embryo, you've got to learn to do it, right? What do you think you're going to learn on?"

"You won't find the answers by looking to the stars. It's a journey you'll have to take by looking at yourself. You must write your own destiny."

--Reeves on Smallville

Still, Senate Majority Leader Bill Frist, R-Tenn., a top Bush administration ally and the only physician in the Senate, has said he supports federal funding of embryonic-stem-cell research.

Reeve believes that kind of support underlines his contention that the president's decision was made for purely political reasons, to placate the religious right.

And he's had private conversations with elected officials who were opposed to research using embryonic stem cells. Some subsequently changed their minds. Others wouldn't budge.

"When Orrin Hatch [R-Utah] was making up his mind about embryonic-stem-cell research, he listened to a wide variety of experts and finally decided that even though he's pro-life, that being pro-life means being for saving lives," he said.

Frist joins a group of anti-abortion politicians including Hatch and Sen. Gordon Smith, (R-Ore.), who have urged Bush to allow the use of federal dollars for research because of the embryonic cells' potential to fight disease.

There's a bill in the Senate that would fund research, but not enough votes to override a promised presidential veto, so it's unlikely the bill will come to the floor during Bush's presidency.

So Reeve is championing a different kind of political effort.

"I think that it will take a grass-roots movement similar to the one that forced the federal government to fund AIDS research in the late '80s," he said. "Today, the NIH spends $1.8 billion a year on AIDS research. That's because the public demanded it."

Reeve said he believes other states will follow the lead of California and pass their own versions of a bill that supports research on stem cells derived from any source.

"When the state-based initiatives succeed," he said, "it will a be a breakthrough for our scientists and an enormous boost for our economy, because it will represent new opportunities for the pharmaceutical companies and encourage new venture capitalists. And once that happens, I don't see the federal government attempting to reverse it."

Doubts About Bone Marrow-Derived Adult Stem Cells Ability To Differentiate
A study led by UCSF investigators indicates that bone marrow-derived cells from mice that are transplanted into other mice fuse with cells in the animals’ heart, brain and liver, and take on their characteristics. The finding is significant in part because it offers strong, new evidence that bone marrow-derived cells do not actually differentiate into specialized cells themselves, a goal of some cell-transplant therapy.

The findings, reported in the advance, on-line issue of Nature on Oct. 12, contrast with previous studies that have suggested adult stem cells derived from the bone marrow -- a spongy tissue inside bones that makes blood cells -- were capable of specializing not just into blood cells, but into cells of the brain, heart and other tissues. These studies have raised hopes that cells that are progenitors of blood could be used to replace damaged tissue in critical organs.

The new findings provide the first indication that cell fusion, rather than differentiation, occurs when bone marrow-derived cells migrate to the heart and the brain of mice. They also support previous studies showing fusion of blood cells in liver, and in cell-culture.

Given this evidence, the researchers say, clinical trials to study whether implanted bone marrow-derived cells could be used to replenish damaged cells in patients with diseases of the heart, brain and liver should be postponed until more research has been conducted.

“Our study raises serious questions about whether bone marrow-derived cells are capable of trans-differentiation,” says the senior author of the study, Arturo Alvarez-Buylla, PhD, professor of neurosurgery at University of California, San Francisco (UCSF).

“The finding raises major questions about the plasticity of adult blood stem cells,” says co-author Sean J. Morrison, PhD, a Howard Hughes Medical Institute assistant investigator and assistant professor of internal medicine and of cell and development biology at University of Michigan.

At the same time, cell fusion, itself, should be explored further, the researchers write in their paper, suggesting that it might contribute to development and maintenance of some cell types, and could be one of the body’s strategies for repairing damaged cells. “My hunch is that fusion might be a physiological mechanism that the body has devised to import DNA from blood cells into damaged cells in various tissues,” says Alvarez-Buylla.

If fusion does play a role in repair of cells in the body, or even if it doesn’t, the new findings suggest that it might be possible to harness the technique therapeutically, he says. Earlier this year, researchers reported that bone marrow-derived cells fused with damaged liver cells in experimental mice and helped to improve their damaged livers.

In the current study, led by Manuel Alvarez-Dolado, PhD, a postdoctoral fellow in the Alvarez-Buylla lab, in collaboration with the Morrison laboratory, bone marrow cells from one set of mice were grafted into the bone marrow of another set of mice whose own marrow had been irradiated. The cells of both animal models had been genetically engineered to enable the scientists to detect if cell fusion occurred. Later, at one of two time points – two months or four months – the mice were sacrificed and their tissue examined.

The researchers determined that the cells, after circulating through the blood and migrating into different organs, fused with Purkinje neurons in the brain, cardiomyocytes (heart muscle cells) in the heart and hepatocytes in the liver, assuming their structural characteristics. The scientists detected no evidence of trans-differentiation without cell fusion. They did not detect cell fusion in skeletal muscle, gut, kidney or lung in their experiments, though it is possible, they say, that under different experimental conditions fusion might occur in these tissues.

Notably, the fused cells contained two nuclei – one nucleus (which encases the body’s genes) from the original cell and one from the blood cell. As such, they contained two sets of genetic instructions. The work raises the interesting question of how genes are controlled between the two nuclei and whether the genetic information derived from the blood contributes to the function of the host cell, says Alvarez-Buylla.

The current study provides hints, he says, that some of the genes from the bone marrow-derived cells might be down regulated, or inactive, which could explain the fused cells’ healthy appearance. Whether cell fusion can help rescue damaged cells remains to be seen, he says. In any event, he says, the discovery that cell fusion occurs, at least in an animal model, “opens up some very interesting questions about how one cell dominates over another to maintain a functional hybrid.”

“The fact that adult bone marrow-derived cells fused with pre-existing local cells, rather than trans-differentiating into new cells, under the experimental conditions that we used, means that they may do the same in the human body,” says Morrison. “Therefore, clinical trials that are based on the idea that bone marrow cells can generate new cells in tissues like the heart should be re-evaluated. We urgently need a better understanding of the functional effects of cell fusion, the circumstances under which it occurs, and what cells are capable of fusing

Preliminary Study Finds Stem Cells In Blood Restore Damaged Heart Muscle
HOUSTON -- Based on promising animal data, researchers at The University of Texas M. D. Anderson Cancer Center say that cells taken from a patient's own blood may one day be able to repair heart tissue that has been damaged.

While other researchers have shown that stem cells derived from bone marrow and umbilical cord blood can regenerate cardiac tissue, this study demonstrates that adult stem cells circulating in blood can also repair a heart.

In the study, published online in the current issue of the journal Circulation, the scientists found that human blood stem cells -- "master" cells that produce other types of body cells as needed -- regenerated heart muscle cells as well as artery tissue in mice whose hearts were injured.

"This takes us a big step ahead," says the lead author, Edward T. H. Yeh, M.D., professor and chair of M. D. Anderson's Department of Cardiology. "Taking stem cells from blood is a lot easier, and a lot less painful, than taking it from bone marrow.

"For patients, it would be as simple as donating blood," he says. "We would then isolate these potent cells and give them back to the patient where the damage has occurred."

While the researchers are cardiologists and cancer specialists, and are interested in treating heart failure that occurs in up to 10 percent of patients who use chemotherapy, they say such cell-based regeneration therapy could benefit patients who have had a heart attack or other injuries that have led to heart failure. "Such a therapy cannot bring back dead heart muscle, but it can help restore weakened hearts, no matter what the cause of the damage was," says Yeh.

The research also contributes more evidence to the idea that stem cells circulating in the blood can transform themselves into different organ systems as needed to repair injury -- a notion dubbed "stem cell plasticity" that is both revolutionary and controversial. The theory, pioneered by M. D. Anderson researchers Martin Körbling, M.D., and Zeev Estrov, M.D., upsets longstanding beliefs that different kinds of tissue have their own supply of stem cells to repair damage. If correct, however, stem cell plasticity could be used to repair, or even replace tissues and organs injured by cancer, say Körbling and Estrov, who are co-authors on this study.

To conduct the study, the researchers collected a supply of human stem cells from what is generally regarded as debris from the process of banking human red blood. (After blood is collected from volunteers, it is separated into white and red blood cells, and the white blood cells are usually thrown away.) The scientists collected white blood cells and then searched for those cells that express a protein (CD34+) that is known to be associated with stem cells. They then isolated cells with the CD34+ marker from the white cells.

To test whether peripheral blood stem cells could regenerate tissue, the research team used two groups of mice that were engineered not to have an immune system, so that they would not reject human cells. One group of mice was given an artificially induced heart attack, and then immediately treated with an injection of the human stem cells. The other mice, with healthy hearts, also received the stem cell therapy.

The researchers found that in mice with an injured heart, new cardiac muscle cells (myocytes) had developed at the edge of damaged tissue, and several layers of new blood vessel tissue (endothelial and smooth muscle cells) had also grown. Little evidence of such repair was found in the mice with healthy hearts, says Yeh.

"We've shown that CD34+-associated cells can actually transform into three different cells used by the heart, and that tissue damage is critical to this process," he says.

Several sources for regenerative stem cells have been suggested, such as bone marrow, cord blood and embryonic cells, but this study "demonstrates that adult blood stem cells may be an alternative to these other sources of cells for myocardial regeneration," says Yeh. "And blood is a readily available source of stem cells that does not require significant manipulation."

Yeh notes that no stem cell protocol has been approved in the United States to date, and that most human trials using stem cells (those derived from bone marrow) have taken place in Europe and South America. Still, Yeh says he hopes his research can advance in the near future

WHEAT RIDGE, CO -- (MARKET WIRE) -- 10/22/2003 -- GeneThera, Inc. (OTC BB: GTHA) is pleased to announce that Dr. Henry Wei has joined the GeneThera team as Director of Assay Development. Dr. Wei comes to GeneThera from an illustrious career in stem cell research and drug discovery. Most recently, Dr. Wei worked for Geron Corporation, a biopharmaceutical company located in California.

Dr. Wei has extensive experience utilizing PCR technology for gene expression assays. While working at Geron Corporation, Dr. Wei characterized gene expressions for 213 genes in many different human tissues and cells. Dr. Wei graduated with a Ph.D. from the University of Minnesota School of Medicine and completed his postdoctoral training at Yale University School of Medicine.

"I am extremely excited to have the opportunity to apply my knowledge of stem cell research to GeneThera's Integrated Technology Platform," Dr. Henry Wei stated.

Dr. Antonio Milici, CEO of GeneThera, commented, "The addition of Dr. Wei to our research team has already helped us achieve major breakthroughs in the development of our diagnostic tests and therapeutic vaccines."

When adult stem cells divide, they give rise to more stem cells, in addition to mature cells that replace dead or damaged cells in the body. So, the ability of adult stem cells to divide throughout life is necessary for the maintenance of adult tissues.

Most cells in the body are programmed to stop dividing after a limited number of cell divisions, but adult stem cells and cancer cells have the ability to continue making identical copies of themselves for long periods of time, if not indefinitely. Exactly how they do this has remained a mystery – one that scientists all over the world are trying to solve.

"This paper defines one of the mechanisms that make stem cells special," Morrison says. "We now know that Bmi-1 is an important part of the mechanism used by stem cells to persist through adult life. Certainly there are other genes involved and we need much more research to fully understand the process, but Bmi-1 is a major key to unlocking this important mechanism of self-renewal."

Since cancer cells share the secret of self-renewal with adult stem cells, Morrison says his research "raises the possibility that inappropriate activation or over-expression of Bmi-1 in stem cells could lead to uncontrolled growth and cancer."

LONDON (Reuters) - Scientists have discovered a way to increase production of stem cells in mice in a finding that could help cancer patients in need of bone marrow transplants.

The researchers identified a way to stimulate the blood-forming stem cells so that they will reproduce.

"The ability to enhance the number of stem cells an individual produces could have an immediate impact on patient care," Dr David Scadden of Massachusetts General Hospital, who headed the research team, said in a statement on Wednesday.

Hematopoietic stem cells, which can turn into any type of blood cell, are found in the outer layer of bone marrow. But they usually occur in small numbers and are not very good at reproducing.

Cancer patients who cannot produce enough stem cells may not be eligible for a bone marrow transplant, a treatment that could be their best hope for survival.

The scientists, who reported their findings in the science journal Nature, discovered while studying genetically modified mice that the parathyroid hormone could double the output of the blood-forming stem cells.

The key to the whole process was the bone-forming cells, called osteoblasts, they added.

ANN ARBOR, MI – Scientists at the University of Michigan Comprehensive Cancer Center have identified a gene that controls the amazing ability of adult stem cells to self-renew, or make new copies of themselves, throughout life.

In a series of extensive cell culture and animal studies, U-M scientists discovered that a gene called Bmi-1 was required for self-renewal in two types of adult stem cells – neural stem cells from the central nervous system and neural crest stem cells from the peripheral nervous system. In a previous study, other U-M scientists found that Bmi-1 also was necessary for continued self-renewal in a third variety of blood-forming or hematopoietic stem cells.

"So far, we and our colleagues have studied three important types of adult stem cells and Bmi-1 appears to work similarly in every case," says Sean Morrison, Ph.D., an assistant professor of internal medicine in the U-M Medical School and a Howard Hughes Medical Institute investigator. "This raises the intriguing possibility that Bmi-1 could be a universal regulator controlling self-renewal in all adult stem cells."

The U-M study of Bmi-1's role in central nervous system (CNS) stem cells and neural crest stem cells from the peripheral nervous system (PNS) will be published Oct. 22 in Nature's advance online edition.

Co-first authors are Anna Molofsky, a student in the M.D./Ph.D. program at the U-M Medical School, and Ricardo Pardal, Ph.D., a U-M research fellow. Previous U-M research on Bmi-1 and hematopoietic stem cells was conducted by In-Kyung Park, Ph.D., research investigator, and Michael F. Clarke, M.D., professor of internal medicine. Results from that study were published in Nature on April 20.

In a wide-ranging interview with Associated Press editors and reporters, the presidential candidate waded into another medical debate, breaking with President Bush’s policy to limit scientific research involving human embryonic cells.

"The day I walk into the Oval Office, the first thing I’m going to do is rescind the Bush administration restrictions on stem-cell research," the Connecticut senator said. "They’re not compassionate. They block work that will save lives and extend lives."

Bush's policy was that research could continue on stem-cell "lines" that existed at the moment of his speech, in August 2001, but that otherwise, embryo research was banned. Even surplus embryos already in the freezer at fertility clinics—where embryos are routinely created and destroyed by the thousands every year—could not be used for medical research and would have to be thrown out instead.

As cancers grow, cells often move out of the original tumour and spread around the body using the blood or lymphatic system, a process called metastasis. These widespread cancers are especially difficult to treat.

Now scientists have discovered that a surface molecule called 5T4, which is present in many different types of tumour, is also produced by embryonic stem cells (ESCs) as the embryo grows and develops.

The team has already harnessed 5T4 in human clinical trials. Because it is expressed in the embryo only, 5T4 should be treated as a foreign invader by the adult body. The team, in collaboration with Oxford BioMedica, has developed a therapeutic vaccine based on eliciting an immune response against cancer cells expressing 5T4.

"The cancer vaccine has been shown to be immunogenic and safe," Stern told New Scientist.

The team is also collaborating with Active Biotech to develop a "magic bullet" based on 5T4. They are using an antibody that latches on to the molecule to seek out tumours and deliver a drug to kill them.

1. Pray that Congress and the medical establishment will have the wisdom and political courage to support only stem cell research that protects human life. Pray that measures supporting embyonic stem cell research will be defeated.

Dr. Floyd Loop, the Clinic's chief executive, and Yitzhak Apeloig, president of Technion-Israel Institute of Technology recently signed a multiyear agreement to work on molecular medicine and biomedical engineering research, starting with five projects in orthopedics and cardiology.

Penn, who works in the cardiovascular medicine and cell biology departments, said his group works with adult stem cells, while Gepstein and his colleagues work with embryonic stem cells.

Penn said researchers already know that if they "manipulate" the heart in the right way, the body's own stem cells will travel to the heart and become blood vessels. The goal now, Penn said, is to "(a) make sure we're recruiting the right stem cells from the bone marrow and (b) convince them to differentiate into cardiac myocytes," or contracting cells.

German MEP Peter Liese, the European Parliament's rapporteur on new proposals for the EU funding of embryonic stem cell research, will argue for a more restrictive approach than that foreseen by the Commission when he publishes his report in early November.

While the Commission envisages EU funding for projects that aim to create new stem cell lines from frozen embryos created for IVF purposes before 27 June 2002, Mr Liese's plan would only allow research to be carried out using existing stem cell lines created before August 2001. ( [?]  [!] )

Furthermore, Mr Liese would like to see priority given to projects that aim to carry out research using adult stem cells. ( [huh] )

Details of the proposals contained in the draft report were outlined to journalists at a press conference in Strasbourg, France, on 22 October. A vocal opponent of embryonic stem cell research, Mr Liese stated that there are compelling reasons to completely exclude this type of activity from the EU's research programmes, but accepted that such a position would be unlikely to produce a political agreement.

In drafting his proposals, Mr Liese drew extensively on US guidelines for public funding of stem cell research where, similarly, scientists must work with stem cell lines procured before 7 August 2001. Mr Liese's argument is that stem cells from those lines used by publicly funded researchers in the US can be sent to Europe for use in EU projects.

'This compromise represents a very great concession by opponents of embryonic stem cell research to its supporters,' concluded Mr Liese.

The molecular mechanisms controlling inductive events leading to the specification and terminal differentiation of cardiomyocytes are still largely unknown. We have investigated the role of Cripto, an EGF-CFC factor, in the earliest stages of cardiomyogenesis. We find that both the timing of initiation and the duration of Cripto signaling are crucial for priming differentiation of embryonic stem (ES) cells into cardiomyocytes, indicating that Cripto acts early to determine the cardiac fate. Furthermore, we show that failure to activate Cripto signaling in this early window of time results in a direct conversion of ES cells into a neural fate. Moreover, the induction of Cripto activates the Smad2 pathway, and overexpression of activated forms of type I receptor ActRIB compensates for the lack of Cripto signaling in promoting cardiomyogenesis. Finally, we show that Nodal antagonists inhibit Cripto-regulated cardiomyocyte induction and differentiation in ES cells. All together our findings provide evidence for a novel role of the Nodal/Cripto/Alk4 pathway in this process.

Graft Versus Host Disease

New methods of separating stem cells from all other blood components associated with Graft Versus Host disease have resulted in a product that consists of only stem cells. Since these umbilical cord stem cells are immature and have not developed ABO and HLA antigens on their surfaces, they do not induce graft versus host reactions that may occur with embryonic, bone marrow stem cells or to a lesser degree, cord blood. Since the umbilical cord stem cells do not contain mature blood or tissue cells, foreign protein reactions do not occur. This is important because immune suppressive chemotherapies and radiation used in the past with bone marrow and cord blood transplants are toxic to stem cells and new neurons. Both chemotherapy and radiation are associated with neurotoxicity and symptoms of memory loss, depression, and declining IQ scores.

Therefore if "pure" umbilical cord derived stem cells (separated from blood components) are safe enough to use without immune suppressive therapies, the stem cell therapy should be more effective. This is what is being reported from patients being treated in other countries. CD34+ stem cells extracted from cord blood are being reported as safe and effective without the use of immune suppression.

Embryonic lines that are approved for research may be losing their potency over time.

They may contain mouse feeder cells and no longer be "pure" human cells.

In addition, serious Graft Versus Host complications have been reported in patients treated with embryonic stem cells outside the U.S. This could result from embryos having genetic aberrations and diseases from uncontrolled parental sources.

Quality control for purity and potency is a major concern with the use of embryonic stem cells.

We know at this point that a million stem cells per treatment is more effective than 300,000 stem cells and the larger dosage further reduces Graft Versus Host complications. Therefore if "pure" umbilical cord derived stem cells (separated from blood components) are safe enough to use without immune suppressive therapies, the stem cell therapy should be more effective.

Organizers were hoping to use the three-day event as a chance to showcase the tiny island's budding biomedical sector.

With strong governmental support, Singapore has become a center for research into human embryonic stem cells (oh so true) - master cells that can grow into almost any tissue in the body. Scientists hope to use them one day to replace unhealthy cells as a cure for a variety of diseases.

"Most of the big names are here," said Dr. Ariff Bongso, a Singapore scientist who became the first to grow human stem cells without using animal cells in June 2002.

"The whole purpose of this meeting is to show them our Biopolis," Bongso said.

Said its chair of research, Mrs Margery Perry: 'Singapore has taken the lead in showing the world how to deal with stem cell research. That's why we decided to come here.'

The battle over the bill has become a surrogate debate over abortion -- a legal medical procedure in Canada -- because of the implications of whether embryos are human beings. It has also become tangled in the political flux surrounding the transition of power in Ottawa.

"They either go in the garbage or they go to the lab," Liberal legislator Carolyn Bennett, who is a medical doctor, told Reuters.

Much remains to be done before the findings can make a difference in the operating room. Langer and colleagues write that further research is needed to "allay concerns regarding the potential" of embryonic stem cells to turn cancerous. Levenberg said the MIT researchers had tested the cells for normalcy and found that none seemed to have the potential to turn cancerous.

In previous tissue-engineering research, scientists used more-developed stem cells from adult organs. But because these cells proliferate relatively slowly and are specific to particular organs, researchers did not have much success generating new organs.

The lab-made organs also performed better because the mice's blood vessels treated them as normal tissue, sprouting new blood vessels that penetrated into the organs.

In similar experiments using adult cells, this did not occur.

Elaborating on his team's latest findings during a break at the international stem cell conference here yesterday, he added: 'Another plus is that the mother would have been screened for diseases such as HIV and hepatitis B when she gives up the embryo for research, so we would not have to screen the skin sample again.'

Professor Lee Eng Hin, head of the NUS division of graduate medical studies, added: 'This work is very exciting because you need cell lines to be completely animal-free if research is to be taken from the bench to the bedside.'

The research was published last month in the journal Stem Cells.

ES Cell is now working on creating colonies of the unprogrammed cells that can be used safely for trials in patients.

But currently, cell lines, including those developed by Singapore-based ES Cell International and a handful of other companies worldwide, are nourished with animal cells.

This means they cannot be used in trials involving people because of the danger of transmitting animal diseases.

"The corporate repercussions are gathering with this policy," Scott said. "Geron, arguably the best stem cell company in the world, is now down to 50 percent of its employees."

Scott said that some top biologists in the field have left to the Pacific Rim, where the research is encouraged, and CEOs have threatened to resign.

"There are actually venture firms here in the United States that are losing to Japan to do this research," he said.

Scott said that Bush's administration has been inconsistent in its views because it still funded the creation of embryos for in vitro fertilization.

"It's OK to produce a dozen or so embryos in a clinic in the attempt to become pregnant, but it's not OK to produce some for the intention of stem cell research," Scott said.

BOSTON (AP) - Massachusetts would actively encourage research using stem cells, gathered in part from embryos discarded from fertility clinics, under a proposal to be unveiled by Senate President Robert Travaglini on Thursday.

Supporters of the proposal - included in a $115 million stimulus package designed to help jumpstart the state's flagging economy - say they want to follow in the footsteps of California, which passed a first-in-the-nation law last year allowing stem cell research.

"This sends a message to the biotech industry that the state is going to support your efforts to do embryonic stem cell research," said Ann Dufresne, a spokeswoman for Travaglini. "We have the potential to make medical breakthroughs for a whole host of illnesses."

Dufresne said the measure would only allow research on donor embryos that are not going to be used by couples. She said the issue received a public hearing earlier this year when lawmakers took testimony on a similar bill.

Stem cell research is a relatively new issue on Beacon Hill.

In April, lawmakers held a hearing on a bill sponsored by Sen. Cynthia Creem, D-Newton, that would make Massachusetts the second state in the nation to authorize such research, while imposing a ban on reproductive cloning.

The Human Embryo Protection Act would protect living human embryos from intentional destruction. "What this would do is say no public or private entity in Wisconsin could create human embryos, destroy them, transfer, sell or buy them for the purpose of medical research," Lyons said.

The proposed law is a major issue here in Wisconsin because it was researchers at UW-Madison who in 1998 began experiments on living human embryos obtained from infertility clinics. "(The law) essentially would prohibit what they're doing at the University of Wisconsin and prohibit private companies from engaging in the same activity," Lyons said.

Lyons says researchers want to develop clones to use in their experiments. Eventually this usually leads to the destruction of human embryos.

"They're working on developing an artificial womb," she said. "When you have an embryo, you just have cells, but when you put the embryo into an artificial womb it grows -- you've got livers, kidneys and hearts. -- It&