This just in ...

During the past several months, we have seen some extraordinary progress in stem cell research. As I previously reported, last month, a private company known as Geron Corp., based in Menlo Park, CA (near Stanford University) reported that they had successfully transformed human embryonic stem cells into the pancreatic beta cells. The cultured beta cells released insulin in response to glucose, something which earlier efforts failed to do. This research, funded by a private company, is not subject to any of the limits the Bush Administration has placed on embryonic stem cell research using Federal Funds. Proponents quickly seized upon this finding, combined with another study that suggested adult stem cells were not involved in beta cell development as justification for continued funding into embryonic stem cell research.

But just a few weeks later, another announcement that researchers had successfully engineered adult stem cells taken from human umbilical cord blood to make insulin appeared to mitigate the argument. However, one of the researchers did say "It doesn't prove that we're going to be able to do this in people - it's just the first step up the rung of the ladder," Dr Urban said in a statement. Also, its worth noting that its unclear whether these cells responded properly to glucose.

Personally, my perspective is that I don't care whether a cure is derived from embryonic stem cells, or adult stem cells, as long as it works. But I take issue with people who try to ban embryonic stem cell research as somehow destroying a human life when we're talking about embryos created in fertility clinics that are destined for the trash anyway. In effect, they are saying that the life of a blastocyst is more valuable than my life, which I find personally offensive. You may not agree, and that is your prerogative.

But I just received an e-mail that indicated that four independent teams of stem cell researchers had successfully converted adult stem cells from mice into embryonic stem cells, which could be great news. It remains to be seen whether this is a viable alternative to embryonic stem cell research, but if the process works, then it could relegate the entire debate about embryonic vs. adult stem cell research to the trash. Lets hope that is the case!


Scientists Claim Breakthrough In Stem-Cell Research
By Gautam Naik, The Wall Street Journal
June 6, 2007 1:21 p.m.

In a move that may overcome key ethical quandaries of stem-cell research, researchers have created embryonic stem cells without using eggs or destroying embryos.

In experiments on mice, four independent teams of scientists pulled off a feat that's the biological equivalent of turning back time: They returned old, mature cells - such as skin - to their primordial, embryonic state. Further experiments showed that the derived cells had the same properties as true embryonic stem cells, such as the ability to turn into muscle, heart, nerve and other tissue types; some even contributed to the creation of baby mice. Crucially, three of the experiments didn't use eggs and didn't require the destruction of embryos.

"We've shown that we can reset the clock," said Rudolf Jaenisch, a scientist at the Whitehead Institute for Biomedical Research in Cambridge, Mass., and lead author of one of the studies, which is published in the journal Nature. However, he caution, "we're very far away from this being turned into routine medical treatment."

The latest advances come at a time when America's nascent stem cell industry, after being hobbled by years of controversy and regulation, is set for a big boost. Since 2001, the Bush administration has banned federal funding of human embryo research and pushed for alternative approaches. However, many candidates for the U.S. presidency - Republican and Democrat -- support human embryo research, suggesting that funding could dramatically increase after the next presidential election. In addition, several states have started paying for such experiments themselves. California has pledged $3 billion over a decade.

All manner of stem cell techniques, including controversial embryo-experiments and the newer reprogramming approaches, could benefit. "States will pour more money into this research. We'll all get more money," predicts Kevin Eggan, a scientist at Harvard Stem Cell Institute, and lead author on one of the new papers.

Embryonic stem cells are primitive master cells that may one day help treat a wide range of diseases. One obvious idea is to extract the cells from an embryonic clone of a patient, and then convert them into whatever kind of tissue is needed. That tissue can then be transplanted to treat a patient's disease. Since the derived tissue has the same genetic make-up as the patient, the immune system won't reject the transplanted tissue. The big limitation: it requires the creation and destruction of human embryos.

A far less controversial source are known as adult stem cells. Different parts of our body contain a small number of these special regenerative cells whose main function is to replenish dying tissue as the body ages or gets damaged. These special cells can also be manipulated to create other tissue types; thus, adult stem cells found in bone marrow can be turned into fat or cartilage. But these cells can't produce as many tissue types as embryonic stem cells.

Scientists have now turned their attention to another, more unlikely source: old, mature cells. Though these cells have already committed to being a specific type of tissue, such as skin, the latest research suggests that these cells, too, can be returned to a primordial "embryo-like" state. "This is very exciting basic research with tantalizing data," says Robert Lanza, vice president of research and scientific development of Advanced Cell Technology Inc., based in Alameda, Calif. (Dr. Lanza has read the four papers but wasn't involved in any of them.)

It all started with the birth of Dolly a decade ago. Scientists in Britain created the cloned sheep by taking genetic material from the mature skin cell of Dolly's "mother," and substituting it for the genetic material inside the nucleus of another sheep's egg. To their surprise, the egg mysteriously "reprogrammed" the skin cell and returned it into an embryonic state -- from which Dolly was then born. The experiment involved cloning, an obviously controversial move if applied in humans. But, for a small group of scientists, it triggered an intriguing question: Could mature cells be reprogrammed in other ways that don't require cloning?

Shinya Yamanaka of Kyoto University made the big breakthrough. In a study published in 2006, he and a colleague showed that by inserting four specific genes into a mature mouse cell, they could reprogram it to an embryonic-like state. "It was remarkable," says Konrad Hochedlinger of the Harvard Stem Cell Institute and lead author of one of the new papers. "A lot of people didn't believe it."

Now, three separate studies have confirmed that technique and pushed it a few steps forward. Dr. Yamanaka and Dr. Jaenisch are lead authors of two separate papers appearing Nature; the third study, led by Dr. Hochedlinger, appears in a new journal called Cell Stem Cell.

Each of the research teams focused on four specific genes that Dr. Yamanaka had identified last year. Using viruses as a transport vehicle, the scientists inserted the four genes into mature mouse cells and were able to return it to their youthful, embryonic stage. To prove that the new cells can do anything a traditionally derived embryonic stem cell can do, they placed the reprogrammed skin cells into other mouse embryos. The new cells were accepted and incorporated into the live mice that were later born. In addition, the genetic information was successfully passed on to their progeny.

All the experiments were done in mice; achieving the same result in humans is likely to be a far tougher challenge. For one thing, no one knows if the same four genes that reprogrammed mice cells would do the same for humans. And at least two of the genes are known to trigger cancer; indeed, 20% of the baby mice born in Dr. Yamanaka's latest batch of experiments developed tumors. "I would predict that making [embryonic-like] cells from human cells is more demanding," said Dr. Yamanaka, via an email.

In a fourth feat of cellular reprogramming, also appearing in Nature, scientists at Harvard produced embryonic stem cell lines by using fertilized eggs of mice (essentially one-celled embryos). This, too, has huge implications if it can ever be replicated in humans. Getting unfertilized eggs from women for the purpose of experiments is expensive, invasive and, in some states with stringent rules, extremely difficult. However, thousands of fertilized eggs are stored in freezers at IVF clinics across the country. Many are damaged and would never result in a baby if implanted in a woman's womb.

The Harvard scientists showed that even these damaged fertilized eggs can reprogram an adult cell and return it to its embryonic state. DNA from an adult cell was inserted into a fertilized egg; the egg served as host, and provided the chemical signals necessary for creating embryonic stem cells. "We don't know if it will work in humans," said Dr. Eggan of Harvard, noting that his lab was now gearing up for such experiments. But the mouse research suggests that scientists can now "use the large number of fertilized embryos in IVF clinics that are routinely discarded."

Write to Gautam Naik at gautam.naik@wsj.com

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