When it comes to research on HIV and AIDS treatments, it can be hard to know when to celebrate a small advance–everyone wants to see progress, but so many experimental avenues that seemed promising have turned out to be dead ends. Still, a new study that tried a sophisticated form of gene therapy as an HIV treatment seems cause for cautious optimism. If it bears out under further testing, the technique could lead to a one-shot, long-lasting treatment that could replace the punishing regimen of daily medications.
Treating HIV currently comes down to managing the viral load with a mixture antiretroviral drugs. Researcher John Rossi and his colleagues tried to craft a more direct treatment by genetically modifying the HIV-infected patients’ own blood stem cells and increasing the cells’ ability to fight off the virus. The researchers weren’t able to truly combat the virus in this experiment–the patients’ viral loads remained the same–but their work moved beyond previous attempts in two ways: They successfully modified blood stem cells by giving them anti-HIV genes, and those cells survived for two years in patients.
Earlier clinical studies the group conducted with the same strategy made little headway, but now the researchers have overcome two key obstacles, says Rossi, a molecular geneticist. One is that they managed to stitch the anti-HIV genes into a high percentage of the appropriate stem cells. The other is that the cells lived for a long time. “If we could increase the number of modified cells by 10- or 100-fold, we might be able to stop the virus itself,” says Rossi. [ScienceNow]
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President Obama followed through yesterday on his plan to ease restrictions on stem cell use in research funded by taxpayer money. National Institutes of Health leader Francis Collins announced that the organization has approved 13 new lines of embryonic stem cells for research, and will consider 96 more lines for approval.
In March, Obama lifted President Bush’s restrictions on federally-funded research on embryonic stem cells, which limited research to a handful of lines created before August 2001. Obama could not on his own reverse the Congressional ruling that forbids scientists from using taxpayer money to create new stem cell lines from embryos, but the ruling allows researchers to use cell lines created by others in an ethical fashion. The NIH set up a panel to decide which stem cell lines met strict ethical restrictions. The cells, for instance, have to have been made using an embryo donated from leftovers at fertility clinics, and parents must have signed detailed consent forms [Reuters].
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From reprogrammed skin cells, scientists have made live mice.
The accomplishment is the latest step forward in the exciting new field of reprogrammed cells, which may offer an alternative to embryonic stem cells…. [It's] the most definitive evidence yet that the technique could help sidestep many of the explosive ethical issues engulfing the controversial field [Washington Post]. Two new studies describe the process, and one team of researchers reports producing 27 live mice. While there were abnormalities and unusual deaths with some of the first generation of mice, [the] team produced enough normal mice this way to create hundreds of second and third generation mice [AP].
It was only three years ago that Japanese stem cell researchers found a way to reprogram ordinary skin cells to behave like embryonic stem cells, which are thought to hold vast potential for medical research because they can develop into any kind of body tissue–from heart cells to toenail cells. But researchers didn’t know if the reprogrammed adult cells, known as induced pluripotent stem cells or iPS cells, were capable of differentiating into every type of tissue, the way embryonic stem cells do.
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It was only a few years ago that scientists figured out how to reprogram adult cells to make them act like multipurpose stem cells, but the next discoveries are coming fast and furious. Researchers had previously transformed human skin cells into so-called induced pluripotent stem (iPS) cells that can grow into any type of tissue; now, a new study reports that the same feat has been accomplished with pig cells. The achievement raises the possibility that genetically engineered pigs could be reared as organ donors, researchers say.
The created iPS cells could be genetically altered, and then cloned to produce pigs with certain traits. By adding or deleting certain genes, for example, researchers could produce pigs whose organs can be transplanted into patients without them being recognised and rejected. Efforts to do such xenotransplants have already been under way for at least a decade, but iPS cells are easier to genetically engineer and grow in the lab than pig embryos, opening up new possibilities for xenotransplantation [New Scientist]. Pigs are considered potential organ donors because their organs are already similar to those of humans in size and function.
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Scientists have taken another step in cellular reprogramming that points the way towards the use of a patient’s own cells to treat genetic diseases. In a proof of concept study, researchers took skin cells from patients with a rare condition, Fanconi anemia, which causes skeletal problems and bone-marrow failure, and raises sufferers’ risk of cancer [Technology Review]. In the skin cells, the researchers fixed the genetic defects that caused the disease, and then reprogrammed the cells to act like stem cells capable of growing into any type of tissue.
The corrected stem cells could be grown into blood precursor cells for therapy. As these would carry a patient’s own DNA, except for the mutation responsible for the illness, they could be transplanted without risk of rejection by the body’s immune system [Times Online]. However, the patched up cells were not used to treat patients in this study, because it isn’t yet clear whether such cells are safe. Comments molecular geneticist Chris Mathew: “In future it may become possible to transfer the corrected stem cells back into the patient, but much work remains to be done before this can be transferred from the lab bench to the bedside” [The Scientist].
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Researchers have found a new way to reprogram human skin cells to act like multipurpose stem cells, and say their safe technique produces stem cells that are ready for medical use. If the researchers are right, clinical trials on the induced pluripotent stem (iPS) cells, which can turn into virtually any cell type and potentially be used to treat disorders ranging from spinal cord injury to diabetes, could start within two years [Nature News].
Many experts say that reprogrammed skin cells have several advantages over embryonic stem cells, for reasons both societal and medical. Using adult cells dodges the ethical controversy involved in taking cells from embryos, and it also raises the possibility that patients’ own cells could be used in their medical treatment, negating the chance that the cells would be rejected by their bodies. But reprogramming cells is still a scientific frontier, and researchers have struggled to find safe ways to accomplish the feat.
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The controversy surrounding stem cell research might soon be moot, with new research showing that ordinary skin cells can be transformed into an equivalent of embryonic stem cells, which have been the focus of research because of their ability to become any kind of cell in the human body. This is known as a pluripotent state, and the new research, published in two articles in Nature, marks the first time that scientists have turned skin cells into induced pluripotent stem cells or iPS cells—which look and act like embryonic stem cells—without having to use viruses in the process [Reuters].
Scientists have been able to make stem cells from adult cells for more than a year, but relied on the injection of a virus to trigger the transformation of the cell into the embryonic state. These cells could not be used on patients, however, because of the risk they presented of developing cancer. Now, researchers in Britain and Canada have produced the cells by using strands of genetic material, instead of potentially dangerous genetically engineered viruses, to coax skin cells into a state that appears biologically identical to embryonic stem cells [Washington Post].
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Researchers have coaxed a mouse into releasing a flood of stem cells from its bone marrow, and say these extra stem cells may then hustle off to repair damaged tissue. If this technique proves effective for repairing damage and can be transfered to humans, researchers say it could help mend everything from broken bones to damaged hearts. Says lead researcher Sara Rankin: “Suppose a person comes in to hospital having had a heart attack. You give them these drugs and stem cells are quickly released into the blood. We know they will naturally home in on areas of damage, so if you’ve got a broken bone, or you’ve had a heart attack, the stem cells will go there. In response to a heart attack, you’d accelerate the repair process” [The Guardian].
Researchers say this approach would be a more direct and less controversial way to get stem cells to patients. Instead of injecting patients with stem cells from donors, embryos or stem cell banks, doctors could simply inject the drugs and the patients would produce the cells themselves. This would avoid complications of tissue rejection and sidestep ethical objections to using stem cells originating from embryos. “It’s promoting self-healing,” says Sara Rankin…. “We’re simply boosting what’s going on naturally” [New Scientist].
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In a pioneering new treatment, doctors created a tailor-made new windpipe for a woman out of donor tissue and the woman’s own stem cells, and say the new, transplanted trachea has been accepted by the woman’s immune system as a natural part of her body without the use of powerful immune-suppressing drugs. Martin Birchall, one of the surgeons, said the transplant showed “the very real potential for adult stem cells and tissue engineering to radically improve their ability to treat patients with serious diseases. We believe this success has proved that we are on the verge of a new age in surgical care” [The New York Times]. Similar treatments could soon be tried on transplants of other hollow organs, like the bowel, bladder, and reproductive tract, he said.
The 30-year-old patient, Claudia Castillo, had failing airways and severe shortness of breath due to a bout with tuberculosis. By March of this year, Castillo’s condition had deteriorated to the point where she was unable to care for her children. Removing a lung was one treatment option, which would have allowed her to live, but seriously impaired her quality of life [Forbes.com]. She opted instead for this experimental treatment, in which doctors took a piece of trachea from an organ donor and transformed it into a structure that now appears native to her body.
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Researchers have found a way to turn cells from human testes into adult stem cells, raising the possibility that men could eventually have spare cells from their own testicles converted into other kinds of tissue for medical treatments and bodily “repairs.” Lead researcher Thomas Skutella harvested spermatogonial cells, which normally mature into sperm, from men and used a series of chemicals to turn them into various cell types…. “We made them into skin, structures of the gut, cartilage, bone, muscle and neurons,” says Skutella [New Scientist].
The achievement is of particular interest because it avoids the ethical quandaries involved in using embryonic stem cells, which require destroying a human embryo. Using testicular cells isn’t the only promising method that avoids embryos; there have been impressive experiments in reprogramming ordinary body cells into stem cells by slipping certain genes into them. The new findings and the reprogrammed cells — which still have technical hurdles — “take some pressure off the stem cell issue,” said White House science adviser Jack Marburger [AP].
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Researchers have found a way to create stem cells from adult liver cells without triggering DNA changes that have caused mutations and tumors in previous studies. Though demonstrated only in mice so far, the result marks another key achievement in the fledgling science of cellular reprogramming. The hope is to create human, embryonic-like stem cells — which can be turned into all the other tissue types of the body — without using eggs or destroying embryos. That freshly derived tissue could then be transplanted into patients to treat various diseases [The Wall Street Journal].
A method of using adult cells to create stem cells was debuted by Japanese researchers in 2006. By using viruses to insert key developmental genes, researchers coaxed human skin cells into an embryonic state, capable of growing into almost any other type of tissue…. But there was a catch: Viruses used to reset the cells tended to fuse with their DNA, leading to unpredictable mutations and cancer. The cells were promising in principle, but couldn’t be used medically [Wired News]. In the new breakthrough, researchers used a different kind of virus to introduce the genes, and found that it didn’t leave behind any damaging genetic code.
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In a striking achievement, researchers have taken ordinary skin cells from two elderly women suffering from Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis, and have reprogrammed those cells to act like stem cells, the versatile cells that can grow into almost any kind of specialized cell. Then the researchers programmed the cells to turn into motor neurons, the type of nerve cells that waste away and die as ALS progresses.
The new nerve cells won’t be used in any sort of experimental treatment; instead researchers will look for flaws in these nerve cells to study the disease’s mechanism. “Now we can make limitless supplies of the cells that die in this awful disease. This will allow us to study these neurons, and ALS, in a lab dish, and figure out what’s happening in the disease process,” said [study coauthor] Dr. Kevin Eggan [Reuters]. This is particularly useful for ALS because the nerve cells affected by the disease are in patients’ spinal cords, making it impossible for researchers to take cell samples for study.
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