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Artist of Life
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I remember reading an article on an experiment that may have sucessfully turned human skin cells into stem cells (I'll keep searching for the article).
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National Geographic News
Scientists have turned an ordinary skin cell into what appears to be an embryonic stem cell. The process may eventually eliminate the controversial step of destroying human embryos for stem cell research.
The new technique involves fusing a skin cell with an existing, laboratory-grown embryonic stem cell. The fused, or hybrid, cell is "reprogrammed" to its embryonic state, Harvard University scientists report in the journal Science.
Their paper was published Sunday on the journal's Web site.
The breakthrough may one day quell the debate over stem cell research. But team member Kevin Eggan said the technology is still in early stages and is not a replacement for methods currently used to derive embryonic stem cells.
"This is just beginning of this system," he told reporters in a conference call.
Embryonic stem cells are unspecialized cells. They can grow into any type of cell found in our body.
Scientists hope embryonic stem cells can eventually be used to grow new tissue and replacement organs and to cure a range of ailments, from spinal cord injuries to Alzheimer's disease.
To study embryonic stem cells, researchers developed cell lines from stem cells, which were initially harvested from fertilized human eggs, such as those leftover from in vitro fertilization.
Because harvesting destroys the embryo, in the United States the practice has drawn the ire of many religious conservatives who regard destroying embryos as a form of murder.
New Way
The Harvard research suggests a new way to create embryonic stem cells that may one day eliminate the need to destroy fertilized human eggs.
The new type of stem cells is essentially a rejuvenated version of a person's own skin cells. A stem cell created by the new method would have DNA identical to that of the skin cell donor.
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Here are some recent breakthroughs for your pleasure.
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Scientists Discover Key to Growing New Stem Cells
Scientists at Duke University Medical Center have demonstrated they can grow human stem cells in the laboratory by blocking an enzyme that naturally triggers stem cells to mature and differentiate into specialized cells.
The discovery may enable scientists to rapidly grow stem cells and transplant them into patients with blood disorders, immune defects and select genetic diseases, said the Duke researchers.
Stem cells are the most flexible cells in the body, continually dividing into new stem cells or into specialized cells that carry out specific roles in the body. But little is known about how stem cells choose their fate. The Duke team focused on "hematopoietic" or blood stem cells.
In their study, the investigators discovered that an enzyme, aldehyde dehydrogenase (ALDH), stimulates hematopoietic stem cells to mature and transform into blood or immune cells, a process called differentiation. They inhibited this enzyme in stem cell cultures and successfully increased the number of stem cells by 3.4 fold. Moreover, they demonstrated the new stem cells were capable of fully rebuilding the blood-forming and immune systems of immune-deficient mice.
Results of the study are published on line and will be published in the August 10, 2006, issue of the Proceedings of the National Academy of Sciences.
"Our ability to treat human diseases is limited by our knowledge of how human stem cells determine their fate -- that is, whether they maintain their ability to self-renew or whether they go on to become specialized cells," said John Chute, M.D., associate professor of medicine in the Duke Adult Bone Marrow and Stem Cell Transplant Program. "Unraveling the pathways that regulate self-renewal or differentiation in human stem cells can facilitate our ability to expand the growth of human stem cells for therapeutic uses."
Currently, patients who require stem cell transplants are given either bone marrow from adult donors, umbilical cord blood derived from newborn babies, or stem cells from blood. But stem cells are scarce, representing less than 0.01 percent of the bone marrow cell population. Likewise, cord blood units frequently lack sufficient numbers of stem cells to rebuild a patient's decimated immune system.
Efforts to grow human hematopoietic stem cells in the laboratory have proven extraordinarily difficult, Chute said, because growth factors in culture make stem cells rapidly differentiate. The scientists searched for ways to block a stem cell's natural propensity to differentiate without promoting uncontrolled growth.
The researchers focused on the ALDH enzyme because it is a telltale "marker" that distinguishes stem cells from other blood and immune cells. Moreover, it is known to play an essential role in the body's production of retinoic acids, which regulate cell differentiation in a variety of tissues. Yet how ALDH functions in stem cells remained unknown, Chute said.
The scientists began by analyzing how stem cells behave under normal circumstances when grown in culture. They mixed together purified human stem cells with growth factors that induce stem cells to mature and differentiate. As expected, the stem cells showed a marked decline in number as they differentiated into other types of specialized cells. By day seven, all stem cells had disappeared from culture.
The scientists then added an inhibitor of ALDH to the stem cell cultures, and they found that half of the stem cells maintained their immature and undifferentiated status. Moreover, adding the inhibitor caused a 3.4-fold increase in stem cell numbers within seven days.
Next, the scientists transplanted the cultured stem cells into immune-deficient mice to determine how the stem cells would behave. The new population of stem cells migrated to the bone marrow as expected and successfully "engrafted," or took hold in the bone marrow, where they began to produce new blood and immune cells.
"ALDH appears to play a fundamental role in the differentiation program of human hematopoietic stem cells," Chute said. "Inhibition of this enzyme facilitates the expansion of human hematopoietic stem cells in culture."
Chute said their results reveal a unique role for both ALDH and the process of retinoic acid signaling in human stem cells. Chute and colleague Donald McDonnell, Ph.D., professor of pharmacology and cancer biology, are currently testing whether they can directly block the retinoic acid receptors in stem cells and produce a comparable expansion of human stem cells.
The investigators plan to develop a clinical trial to test their approach to expand human stem cells for therapeutic purposes.
Source: Duke University Medical Center
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Stem cells engage in dialogue with cells that regulate their future
These two images show fruit fly stem cells (orange/pink stained cells) in their niche (first image) and leaving their niche (second image). Note the orderly manner in which the stem cells line up and then leave the niche.
Dialogue, not a monologue, is the basis of all good communication. Stem cells are no exception. Recent University of Washington (UW) research has found an early indication of two-way cellular communication. This two-way cell-to-cell signaling occurs in the miniscule niches of the body where the futures of stem cells are determined.
Stem cells require these niches - nest-like microenvironments made up of regulatory cells -- in order to self-renew. Stem cells can divide and turn into many types of new cells. The niches help regulate the amount and kinds of new cells produced to meet current demands.
The niches also help maintain a supply of stem cells for later use. Inside your body, for example, there are separate niches for stem cells that will become blood, for cells that will become skin, and so on. Niches are places where your stem cells can replenish themselves and your tissue cells throughout your lifetime.
Problems in the niches can lead to diseases in the body. For example, if cell multiplication in a niche gets out of hand, cancer might form. A decline in cell production might contribute to the frailty of old age.
While a few stem-cell niches have been known for a long time, what's been harder to discover are the characteristics of the cells making up these niches and how they make it possible for stem cells to do their job. Signaling between cells in the niche plays a role in stem-cell upkeep and development. Most research has focused on the signaling of niche cells to stem cells.
"We looked at the possibility that two-way communication exists between stem cells and niche cells,"said UW stem-cell niche researcher Hannele Ruohola-Baker, professor of biochemistry and a member of the UW Institute for Stem Cell and Regenerative Medicine. "Demonstrating that stem cells can contribute to niche function has far-reaching consequences for stem-cell therapies and may provide insight on how cancer might spread throughout the body via populations of cancer stem cells.”
Ruohola-Baker added that stem cells hold high hope in regenerative medicine: tapping into the ways cells repair the body to create therapies to fix or replace injured tissues. She mentioned that it is thought that most, if not all, adult tissues contain stem cells.
Through self-renewing division,"she explained, "stem cells replenish the stem cell pool. They also produce progeny that change into other, specialized cells. Importantly, stem cells have the capacity to divide throughout the life of an organism. They do so through regulated external stimuli that may initiate from stem cells. This regulation of cell division needs to be tightly controlled."Too little division results in poor maintenance of tissues, while too much can result in tumors or other malignancies.
Her lab used the germline stem cell niche, found in the ovaries of fruit flies, as a model system. The production of fruit fly eggs depends on the presence of a renewable source of stem cells in the ovary of the adult fruit fly.
Inside the fruit fly ovary are structures called germarium which contain tiny cradles made of cap cells that nurture stem cells. Each such cradle contains two to three stem cells preparing to become fly eggs that are cuddled in a niche composed of three to six cap cells. Cap cells adhere to stem cells and this close contact may allow cap cells to play critical roles in communicating with stem cells.
The research team looked at a kind of signaling that usually depends on direct contact between cells, called the Notch pathway. The Notch protein is like a trigger poking out of a cell that can activate a mechanism inside the cell. When this trigger is pulled by proteins, called Delta and Serrate, from another cell, proteins are freed inside the cell to travel to the cell nucleus and turn on various genes.
According to Ruohula-Baker, the Notch pathway plays an important role in many stem-cell niches, including those in the blood system, gut, breasts, and muscles. However, in many cases it hasn't been clear which cells send and which ones receive the signaling protein.
The UW researchers analyzed the role of the Notch signaling pathway in both the stem cells and the cap cells. They found that either an increased production of Delta protein in the stem cells, or the presence of activated Notch protein in niche cells, resulted in up to 10 times the normal number of niche cells. These extra niche cells in turn resulted in a larger population of stem cells.
On the other hand, when stem cells don't produce functional Delta protein, they cease to be stem cells and soon leave the niche. The researchers also found that the receiving end for the Notch pathway, the trigger, is required in the niche cells, making them receivers of signals, not just senders. Work by other scientists had shown that TCF-beta signaling from niche cells is required to maintain active stem cells.
"Our study now shows that stem cells use the Notch pathway to signal to neighboring cells to maintain an active niche, and in turn, the niche induces and maintains the fate of the stem cells,"Ruohola-Baker noted. "This is a first indication of a dialogue taking place between the stem cells and the niche that supports them. It is tempting to speculate that maybe multiple potential niches exist for stem cells in our bodies that can be turned on to action when signaling stem cells are in the neighborhood. It may very well be that the power of cancer cells to spread comes from this natural ability of stem cells to make a home when in a hospitable environment. We all need a home, and stem cells with their strong survival instinct are active homebuilders.”
The study will appear in the Dec. 5 issue of Current Biology, but is already online at the journal Web site. The research was supported by grants from the American Heart Association, the National Institutes of Health, and the American Cancer Society.
Source: University of Washington
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Scientists at an English university have grown a miniature artificial human liver in a major medical breakthrough, British media reported Tuesday.
It is hoped mini-livers could be used to test drugs, reducing the need for animal experiments, help repair damaged livers and eventually produce entire organs for lifesaving transplants, the Daily Mail newspaper reported.
The organ, which is about the size of a thumbnail, was grown using stemcells in blood taken from umbilical cords.
Professor Colin McGuckin, who specializes in regenerative medicine, made the breakthrough with Doctor Nico Forraz at Newcastle University in northeast England.
While other scientists have created liver cells, the Newcastle team are the first to create sizeable sections of tissue from stem cells from the umbilical cord, the Daily Mail said.
The pair extracted blood from the umbilical cords of newborn babies. They were then placed in a "bioreactor" developed by NASA, which mimics the effects of weightlessness. This allows the cells to multiply more quickly.
Chemicals and hormones are then added to encourage the stem cells to turn into liver tissue.
"We take the stem cells from the umbilical cord blood and make small mini-livers," said McGuckin. "We then give them to pharmaceutical companies and they can use them to test new drugs on.
"When a drug company is developing a new drug it first tests it on human cells and then tests it on animals before beginning trials on humans," he said.
And he added: "Moving from testing on animals to humans is a massive leap and there is still a risk. But by using the mini-livers we have developed there is no need to test on animals or humans."
They could potentially be used like dialysis machines, buying time for a patient's liver to repair itself or for doctors to find a replacement liver.
Professor Ian Gilmore, a liver specialist at the Royal Liverpool Hospital in northwest England, told the BBC that the Newcastle team had made a "big ethical leap forward" in not requiring embryos to produce tissue.
"It is exciting because there is a real dearth of treatments available for people with liver disease," he said.
It is estimated that up to 10 percent of the British population have liver problems, mostly linked to lifestyle factors such as obesity and alcoholism, the BBC said.
© 2006 AFP
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Last edited by Ch'i; 11-03-2006 at 05:30 PM..
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10-30-2006, 11:20 AM
