A team of Canadian scientists identified 1,155 genes under the control of a single gene called Oct4, the master regulator of the stem cell state. Researchers developed a comprehensive definition of stem cells on a molecular basis such that stem cells keep their DNA packed in a flexible format, keep cell division tightly controlled, prevent signals that trigger death and repair DNA. “You could call this a 'theory-of-everything' for stem cells,” said Michael Rudnicki, senior scientist at the Ottawa Health Research Institute.
Newswise — Researchers at the Institute for Stem Cell Biology and Medicine at UCLA were able to take normal tissue cells and reprogram them into cells with the same unlimited properties as embryonic stem cells, the cells that are able to give rise to every cell type found in the body.
The work, done in mouse models, appears in the inaugural June 7, 2007 issue of Cell Stem Cell, published by Cell Press. UCLA researchers, working closely with stem cell scientists at Harvard, took mouse fibroblasts, cells that develop into connective tissue, and added four transcription factors that bind to special sites on the DNA. Using this process, they were able to turn the fibroblasts into pluripotent cells that, in every aspect tested, were identical to embryonic stem cells.
The implications for disease treatment could be staggering. Reprogramming adult stem cells into embryonic stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine. If the work can be replicated in human cells, it may mean that a patient’s skin cells, for example, could be reprogrammed to become embryonic stem cells. Those embryonic stem cells could then be prodded into becoming various cells types – beta islet cells to treat diabetes, hematopoetic cells to create a new blood supply for a leukemia patient, motor neuron cells to treat Parkinson’s disease.
University of Pittsburgh scientists said the resistant cells, called cancer stemcells, ultimately become the source of disease recurrence and eventual metastasis. But a team led by Assistant Professor Vera Donnenberg suggested effective chemotherapy must be able to target a small subset of cancer stem cells, which share the same protective mechanisms as normal lung stem cells.
Lanza redeemed the promise of his previous work by announcing a solution to the ethical problems at the 5th International Society for Stem Cell Research meeting. He told the audience his team had made embryonic stem cells from three human embryos that were now safely frozen away. These embryos should be viable since they were treated just the same as other biopsied embryos that go on to produce babies.
Robert Lanza of Advanced Cell Technology in Worcester, Massachusetts announced he has delivered on the promise made last year to produce ESC without harming the embryo. HUMMM
This is very exciting since it could eliminate extraction of blood vessels from a patient undergoing bypass surgury. It also could contribute to understanding the development of blood vessels.
While other species had been cloned, this is the first time primates have been. Since humans are primates, this puts human theraputic (as well as reproductive cloning) one large step closer.
June 18 (Bloomberg) -- Researchers at the University of Tokyo used stem cells from a mouse embryo to grow kidneys in mice lacking the organs, a step toward creating human body parts for transplant patients.
Scientists led by Hiromitsu Nakauchi at the university's Laboratory of Stem Cell Therapy injected embryonic stem cells into juvenile mouse embryos lacking a crucial gene needed to grow kidneys. Once implanted into the uterus, the embryos grew into fetuses with kidneys. Kidneys were grown in three mice. One had minor abnormalities. The others seemed normal, Nakauchi said.
Everything about Shinya Yamanaka's discovery was right—except for the timing. The 44-year-old Kyoto University stem-cell researcher had found a way to genetically reprogram an ordinary mouse skin cell to revert to the virtual equivalent of its embryonic state, in which it has the potential to grow into any kind of tissue. The finding was a promising first step toward the creation of stem-cell lines for near-miraculous medical treatments—and because Yamanaka did not use human embryos, his technique offered researchers everywhere a way to sidestep the ethical controversies that have dogged the field since its birth. But it was March 2006, just months after the South Korean stem-cell scientist Hwang Woo Suk—who had become an international sensation after claiming to have cloned a human embryo, a first—had been exposed as a fraud. As another Asian stem-cell scientist announcing a surprise advance, Yamanaka knew his peers would put him under the microscope. "I was very nervous," he recalls. A few weeks later at a scientific conference in Whistler, Canada, where he delivered his findings to an audience of international colleagues, "I could tell from their tone that many people did not believe me," he says.
Vindication came on June 7, when the rest of the scientific world caught up with Yamanaka. Two separate teams of stem-cell researchers affiliated with the Massachusetts Institute of Technology, Harvard University and the University of California, Los Angeles published papers essentially confirming and refining Yamanaka's findings, while his own team released a new study that improved on his original research. The collective work—which one cloning pioneer compared to turning lead into gold—raises the possibility that scientists might one day be able to reprogram a patient's own adult cells to transform into human embryonic stem cells and then into heart, nerve or any other kind of tissue. That could give doctors the ability to repair or replace cells destroyed by disease or injury, without fear of immune-system rejection. Experts were quick to warn that significant hurdles remained before the technique might ever be used in people, but the sheer simplicity of Yamanaka's discovery—he found just four genes were required to reprogram the mouse skin cells—was cause for elation. "This is great science," says Alan Trounson, professor for stem-cell sciences at Monash University in Melbourne, Australia. "It takes us a big step closer to reprogramming adult cells."
For years, many stem-cell researchers sought to accomplish that through nuclear transfer—transplanting an adult cell's nucleus into an egg that had been emptied of its own genetic material. This process is expensive and difficult, and so far no one has been able to pull it off in humans. Yamanaka never tried. Starting with a tiny team in 1999 at the Nara Institute of Science and Technology—he moved to Kyoto in 2004—Yamanaka focused on finding the genes that could persuade an adult cell to regress on its own to an embryonic state, without the messy mechanics of nuclear transfer. "I thought that since so many people in this field were concentrating on [nuclear transfer], I should concentrate on the opposite," Yamanaka says.
That maverick streak comes naturally to the driven Yamanaka. Many Japanese scientists, even the best ones, can seem detached and dreamy. Though he has only worked in academia, Yamanaka by contrast has the no-nonsense air of the hybrid researcher/entrepreneur, a type that plays a big role in American stem-cell science. "He used to be an orthopedic surgeon, so he has a good sense in connecting his research to a practical application," says Yoshiki Sasai, a stem-cell scientist at the RIKEN Center for Developmental Biology in Kobe. "He's like a venture [capitalist]. He couldn't do big-scale research, so he narrowed his focus and gave everything to it."
Fluent in English—a rarity in Japanese science—Yamanaka worked in the U.S. in the early 1990s. He'll be spending more time in America later this year—he has accepted a post as a visiting scientist at the J. David Gladstone Institute in San Francisco. But his overseas travels will be limited. Yamanaka says he'll remain based in Japan because he doesn't want to pull his children out of high school. He has also been a father figure to younger colleagues—one that isn't afraid to share the credit. "He's a guiding teacher," says Kazutoshi Takahashi, an assistant professor at Kyoto and Yamanaka's first student. "Everyone in the lab gets the opportunity to have their names in big papers."
No one expected those opportunities to come so soon. Trying to discover the right combination of genes that would reprogram adult cells was a scientific fishing expedition in a deep ocean. In early 2004 Yamanaka had worked up a list of 24 possible genes he thought were instrumental in cell programming, and was ready to begin testing them. There was no guarantee any of the 24 suspects were the right ones, and when Yamanaka offered the experiment to one of his students, the researcher turned him down. "We knew the chance that the correct answer was in those 24 factors was very small," says Yamanaka during an interview in his cramped office on the second floor of Kyoto University Hospital. "It was a risky project, and you had to be very brave."
Fortunately, Yamanaka had one student who was brave—or at least, knew when to say yes to his boss. Takahashi spent endless hours screening the candidate genes. "Perhaps this is not something Kyoto University should know, but I worked 365 days a year," Takahashi laughs. Using retroviruses to deliver the genes into mouse skin cells, Yamanaka and Takahashi eventually narrowed the number down to four active genes that triggered the transformation.
That the process proved so straightforward shocked Yamanaka. Scientists had assumed that reprogramming would likely require a complex arrangement of far more genes. "We were very surprised," he says—and with the Hwang debacle on their minds, "we were very worried." Yamanaka had another researcher repeat Takahashi's work, and when they published in the journal Cell in August 2006, he took the unusual step of including every last bit of lab data in the supplementary section of his paper. Still, Yamanaka's results weren't fully accepted until his work was replicated by others—the gold standard of scientific proof.
Now that Yamanaka has helped show science the path, the race is on to discover the researcher's holy grail: a way to reprogram adult cells in human beings. The Japanese pioneer finds himself at a disadvantage. Scientists in the U.S. and Europe can draw on deeper reserves of money and talent. U.S. states such as California and Massachusetts are spending billions of dollars on stem-cell research, hoping to lay the groundwork for development of new medical industries. In contrast, Yamanaka's lab at Kyoto is relatively basic, and the Japanese government has only recently begun channeling real funding into the field. "There is a lack of understanding about how important this research is among government people, and Japanese in general," he says.
For Yamanaka, the temptation exists to flee to greener pastures. But he says that he intends to stay in Kyoto for now, where his discoveries can directly benefit Japan. Besides, his small lab jumped to an early lead, and Yamanaka hints that they may have more breakthroughs in store. "I think that this year or next year we could see [reprogramming] in human cells," he says. "I really believe it could come from our lab." If it does, Yamanaka won't have to worry so much about the skepticism of his fellow scientists.
Glycobiology Research and Training Center and Department of Medicine, University of California, San Diego 92093-0687, USA.
Human embryonic stem cells (HESC) can potentially generate every body cell type, making them excellent candidates for cell- and tissue-replacement therapies. HESC are typically cultured with animal-derived 'serum replacements' on mouse feeder layers. Both of these are sources of the nonhuman sialic acid Neu5Gc, against which many humans have circulating antibodies. Both HESC and derived embryoid bodies metabolically incorporate substantial amounts of Neu5Gc under standard conditions. Exposure to human sera with antibodies specific for Neu5Gc resulted in binding of immunoglobulin and deposition of complement, which would lead to cell killing in vivo. Levels of Neu5Gc on HESC and embryoid bodies dropped after culture in heat-inactivated anti-Neu5Gc antibody-negative human serum, reducing binding of antibodies and complement from high-titer sera, while allowing maintenance of the undifferentiated state. Complete elimination of Neu5Gc would be likely to require using human serum with human feeder layers, ideally starting with fresh HESC that have never been exposed to animal products.
GENE therapy meets stem cells. That is the wave of the future, if the recent annual meeting of the American Society of Gene Therapy in Seattle is any guide. There was a palpable buzz around efforts to correct diseases by targeting therapeutic genes to stem cells already resident in the body.
Clinical trials are on the horizon for treatments for diabetes and a group of fatal neurodegenerative conditions called lysosomal storage diseases. Meanwhile, gene therapists are also using their skills to make "improved" stem cells for regenerative therapies (see "Stem cell enhancement"). "If you look at what is happening today and what is in the pipeline, I think genetic modification of stem cells is going to be a major theme," says Luigi Naldini of the San Raffaele Telethon Institute of Gene Therapy in Milan, Italy.
"People are excited about the potential of stem cells, but most approaches are not leveraging them to their maximum potential," says Madhusudan Peshwa of MaxCyte in Gaithersburg, Maryland. "We're not getting into the driving seat and getting the cells to do what we want them to do."
Many teams have attempted to use adult stem cells in regenerative medicine - to repair damaged tissue after a heart attack, for example -but their efforts have been hampered by problems such as cells dying before reaching their target or not differentiating into the correct cell type.
Now researchers are waking up to the idea of genetically modifying stem cells to enhance their natural attributes and gain a new level of control over them. In the case of heart attacks, stem cells from both skeletal muscle and bone marrow have been shown to repair tissue damage to some degree, either through differentiating into heart muscle cells or releasing chemicals that stimulate existing cells to repair the damage. To make this process more effective, Marc Penn at the Center for Stem Cell and Regenerative Medicine in Cleveland, Ohio, genetically engineered bone marrow stem cells to produce triple the normal amount of a signalling factor called SDF-1. This is an "SOS signal" also released by damaged heart cells after an attack and is thought to recruit repair cells to the damaged area.
"The idea is to try and restart natural signals that initiate repair," says Penn. When the cells were injected into rats' hearts after a heart attack, the team saw a 70 per cent reduction in heart cell death, compared with rats given unmodified stem cells (The FASEB Journal, DOI: 10.1096/fj.06-6558com).
Genomics is a relatively new term that describes the study of all of a person's genes including interactions of those genes with each other and the person's environment. Genomics involves the scientific study of complex diseases such as heart disease, asthma, diabetes and cancer because they are caused more by a combination of genetic and environmental factors. Genomics is offering new possibilities for therapies and treatment of some diseases, as well as new diagnostic methods. The major tools and methods related to genomics studies are bioinformatics, genetic analysis, measurement of gene expression, and determination of gene function.
Scientists have created embryonic stem cells in mice without destroying embryos in the process, potentially removing the major controversy over work in this field. Embryonic stem cells are special because they are pluripotent, meaning they can develop into virtually any kind of tissue type. They therefore offer the promise of customized cells for therapy.
The work, which appears in the June 6 online issue of Nature, was led by Rudolf Jaenisch, a member of the Whitehead Institute and a professor of biology at MIT. His colleagues on the work are from Whitehead, MIT, Massachusetts General Hospital, the Broad Institute of MIT and Harvard, and Harvard Medical School.
Somatic cell nuclear transfer ("therapeutic cloning") offers the hope of one day creating customized embryonic stem cells with a patient's own DNA. In this process, an individual's DNA would be placed into an egg, resulting in a blastocyst that houses a supply of stem cells. But to access these cells, researchers must destroy a viable embryo.
Now, Jaenisch and colleagues have demonstrated that embryonic stem cells can be created without eggs. By genetically manipulating mature skin cells taken from a mouse, the scientists transformed these cells back into a state identical to that of an embryonic stem cell. No eggs were used, and no embryos destroyed.
"These reprogrammed cells, by all criteria that we can apply, are indistinguishable from embryonic stem cells," says Jaenisch.
MADRID - The lower house of the Spanish Parliament voted in favor of a bill on biomedical research that authorizes therapeutic cloning.
The measure, which expressly prohibits reproductive cloning, was supported by all the parties in that chamber with the exception of the main opposition conservative Popular Party.
The link shows how questions in public debate are framed and what effects that framing has on the outcome. The quote gives an example from the recent vote in Congress on ESC funding.
1) Last week, as the House was preparing to vote on legislation that would overturn Bush's limits on funding for embryonic stem cell research, studies published at the journals Nature and Cell Stem Cell reported that mouse skin stem cells could be turned into a pluripotent stem cell with all the characteristics of an embryonic stem cell. Coverage of the studies appeared on the front page of the Washington Post and other newspapers across the country.
Though the research teams connected to the two studies urged Congress to pass the legislation, Catholic and pro-life groups were quick to frame the event as offering a "middle way compromise," adding that moving ahead with embryonic stem cell research was no longer necessary. Others argued, as in this op-ed appearing at the Chicago Tribune, that a conspiracy was afoot to censor the promise of adult stem cell research
Ian Wilmut, who made history when he cloned Dolly the sheep in 1996, is now calling on scientists to inject human DNA into animal egg cells as a workaround to ethical and legal roadblocks. His commentary appears in Nature Reports Stem Cells, an online stem cell resource created by the journal Nature.
