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Stem cell transplant reverses early-stage multiple sclerosis

CHICAGO --- Researchers from Northwestern University's Feinberg School of Medicine appear to have reversed the neurological dysfunction of early-stage multiple sclerosis patients by transplanting their own immune stem cells into their bodies and thereby "resetting" their immune systems.

"This is the first time we have turned the tide on this disease," said principal investigator Richard Burt, M.D. chief of immunotherapy for autoimmune diseases at the Feinberg School. The clinical trial was performed at Northwestern Memorial Hospital where Burt holds the same title.

The patients in the small phase I/II trial continued to improve for up to 24 months after the transplantation procedure and then stabilized. They experienced improvements in areas in which they had been affected by multiple sclerosis including walking, ataxia, limb strength, vision and incontinence. The study will be published online January 30 and in the March issue of The Lancet Neurology.

Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the central nervous system. In its early stages, the disease is characterized by intermittent neurological symptoms, called relapsing-remitting MS. During this time, the person will either fully or partially recover from the symptoms experienced during the attacks. Common symptoms are visual problems, fatigue, sensory changes, weakness or paralysis of limbs, tremors, lack of coordination, poor balance, bladder or bowel changes and psychological changes.

Within 10 to 15 years after onset of the disease, most patients with this relapsing-remitting MS progress to a later stage called secondary progressive multiple sclerosis. In this stage, they experience a steady worsening of irreversible neurological damage.

The 21 patients in the trial, ages 20 to 53, had relapsing-remitting multiple sclerosis that had not responded to at least six months of treatment with interferon beta. The patients had had MS for an average of five years. After an average follow-up of three years after transplantation, 17 patients (81 percent) improved by at least one point on a disability scale. The disease also stabilized in all patients.

In the procedure, Burt and colleagues treated patients with chemotherapy to destroy their immune system. They then injected the patients with their own immune stem cells, obtained from the patients' blood before the chemotherapy, to create a new immune system. The procedure is called autologous non-myeloablative haematopoietic stem-cell transplantion.

"We focus on destroying only the immune component of the bone marrow and then regenerate the immune component, which makes the procedure much safer and less toxic than traditional chemotherapy for cancer," Burt said. After the transplantation, the patient's new lymphocytes or immune cells are self-tolerant and do not attack the immune system.

"In MS the immune system is attacking your brain," Burt said. "After the procedure, it doesn't do that anymore."

In previous studies, Burt had transplanted immune stem cells into late-stage MS patients. "It didn't help in the late stages, but when we treat them in the early stage, they get better and continue to get better," he said.

"What we did is promising and exiting, but we need to prove it in a randomized trial," Burt noted. He has launched a randomized national trial.

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Weizmann Institute Scientists Create Working Artificial Nerve Networks

Scientists have already hooked brains directly to computers by means of metal electrodes, in the hope of both measuring what goes on inside the brain and eventually healing conditions such as blindness or epilepsy. In the future, the interface between brain and artificial system might be based on nerve cells grown for that purpose. In research that was recently featured on the cover of Nature Physics, Prof. Elisha Moses of the Physics of Complex Systems Department and his former research students Drs. Ofer Feinerman and Assaf Rotem have taken the first step in this direction by creating circuits and logic gates made of live nerves grown in the lab.

When neurons – brain nerve cells – are grown in culture, they don’t form complex ‘thinking’ networks. Moses, Feinerman and Rotem wondered whether the physical structure of the nerve network could be designed to be more brain-like. To simplify things, they grew a model nerve network in one dimension only – by getting the neurons to grow along a groove etched in a glass plate. The scientists found they could stimulate these nerve cells using a magnetic field (as opposed to other systems of lab-grown neurons that only react to electricity).

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Researchers study the feasibility of brains made from carbon nanotubes

Synthetic brains are a long way from reality, but researchers at the University of Southern California, funded by the National Science Foundation, are taking the first steps to build neurons from carbon nanotubes that emulate human brain function.

"At this point we still don't know if building a synthetic brain is feasible," said Alice Parker, professor of electrical engineering. "It may take decades to realize anything close to the human brain but emulating pieces of the brain, such as a synthetic vision system or synthetic cochlea that interface successfully with a real brain may be available quite soon, and synthetic parts of the brain's cortex within decades."

The challenges to creating a synthetic brain are staggering. Unlike computer software that simulates brain function, a synthetic brain will include hardware that emulates brain cells, their amazingly complex connectivity and a concept Parker calls "plasticity," which allows the artificial neurons to learn through experience and adapt to changes in their environment the way real neurons do.

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Human induced plurtipotent stem cells reprogrammed into germ cell precursors

<p>Human induced plurtipotent stem cells reprogrammed into germ cell precursors</p>

Discovery may lead to new treatments for infertility

For the first time, UCLA researchers have reprogrammed human induced pluripotent stem (iPS) cells into the cells that eventually become eggs and sperm, possibly opening the door for new treatments for infertility using patient-specific cells.

The iPS cells were coaxed into forming germ line precursor cells which include genetic material that may be passed on to a child. The study appears today in the early online edition of the peer-reviewed journal Stem Cells.

"This finding could be important for people who are rendered infertile through disease or injury. We may, one day, be able to replace the germ cells that are lost," said Amander Clark, a Broad Stem Cell Research Center scientist and senior author of the study. "And these germ cells would be specific and genetically related to that patient."

Theoretically, an infertile patient's skin cells, for example, could be taken and reprogrammed into iPS cells, which, like embryonic stem cells, have the ability to become every cell type in the human body. Those cells could then be transformed into germ line precursor cells that would eventually become eggs and sperm. Clark cautioned, however, that scientists are still many years from using these cells in patients to treat infertility. There is still much to be learned about the process of making high quality germ cells in the lab.

In another important finding, Clark's team discovered that the germ line cells generated from human iPS cells were not the same as the germ line cells derived from human embryonic stem cells. Certain vital regulatory processes were not performed correctly in the human iPS derived germ cells, said Clark, an assistant professor of molecular, cell and developmental biology.

So it's crucial, Clark contends, that work continue on the more controversial human embryonic stem cells that come from donated, excess material from in vitro fertilization that would otherwise be destroyed.

When germ cells are formed, they need to undergo a specific series of biological processes, an essential one being the regulation of imprinted genes. This is required for the germ cells to function correctly. If these processes are not performed the resulting eggs or sperm, are at high risk for not working as they should. This has significant consequences, given that the desired outcome is a healthy child.

"Further research is needed to determine if germ line cells derived from iPS cells, particularly those which have not been created by retroviral integration, have the ability to correctly regulate themselves like the cells derived from human embryonic stem cells do," Clark said. "When we looked at the germ cells derived from embryonic stem cells, we found that they regulated as expected, whereas those from the iPS cells were not regulated in the same way. We need to do much more work on this to find out why."

Clark and her team plan to examine more iPS cell lines and evaluate the resulting germ cells derived from them to determine if the incorrect regulation remains a problem.

Creating germ cells from embryonic stem cells is challenging and the resulting proportions are low – about 10 percent of embryonic stem cells go on to become germ cells. Clark said creating germ cells from iPS cells proved just as challenging. Putting the iPS cells in an environment where germ cells thrive naturally, among fetal gonadal cells, proved to be the key.

Infertility affects about 15 percent of Americans. Current treatments include donor eggs and sperm and surrogacy. If germ cells can be derived from a patients own adult cells using reprogramming followed by germ cell differentiation, this adds an important strategy into the tool box of options currently available to treat infertility, Clark said. A man with a low sperm count, for example, may be able to have more of his own sperm generated to fertilize his partner's egg.

The study took about 2 ½ years, first focusing on growing germ cells from human embryonic stem cells and then from iPS cells. It took just seven days to get germ line precursor cells from the iPS cells, once Clark and her team landed on the appropriate culture environment.

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FDA allows first test of human stem cell therapy

WASHINGTON (Reuters) - The U.S. Food and Drug Administration has cleared the way for the world's first study of human embryonic stem cell therapy, Geron Corp said on Friday.

The California biotechnology company plans to start a clinical trial to try to use the stem cells to regrow nerve tissue in patients with acute spinal cord injury.

"This marks the beginning of what is potentially a new chapter in medical therapeutics -- one that reaches beyond pills to a new level of healing: the restoration of organ and tissue function achieved by the injection of healthy replacement cells," Geron Chief Executive Thomas Okarma said in a statement.

Shares of Geron rose nearly 30 percent to $6.75 in premarket electronic trading on Nasdaq.

The FDA rejected his company's first request to conduct the trial of GRNOPC1, Oligodendroglial Progenitor Cells. It put the trial on hold in May.

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Implants mimic infection to rally immune system against tumors

<p>Implants mimic infection to rally immune system against tumors</p>

Subcutaneous antigen-laden disks successfully marshal T cells against deadly melanoma

CAMBRIDGE, Mass., Jan. 22, 2009 -- Bioengineers at Harvard University have shown that small plastic disks impregnated with tumor-specific antigens and implanted under the skin can reprogram the mammalian immune system to attack tumors.

The research -- which ridded 90 percent of mice of an aggressive form of melanoma that would usually kill the rodents within 25 days -- represents the most effective demonstration to date of a cancer vaccine.

Harvard's David J. Mooney and colleagues describe the research in the current issue of the journal Nature Materials.

"Our immune systems work by recognizing and attacking foreign invaders, allowing most cancer cells -- which originate inside the body -- to escape detection," says Mooney, Gordon McKay Professor of Bioengineering in Harvard's School of Engineering and Applied Sciences. "This technique, which redirects the immune system from inside the body, appears to be easier and more effective than other approaches to cancer vaccination."

Most previous work on cancer vaccines has focused on removing immune cells from the body and reprogramming them to attack malignant tissues. The altered cells are then reinjected back into the body. While Mooney says ample theoretical work suggests this approach should work, in experiments more than 90 percent of the reinjected cells have died before having any effect.

The implants developed by Mooney and colleagues are slender disks measuring 8.5 millimeters across. Made of an FDA-approved biodegradable polymer, they can be inserted subcutaneously, much like the implantable contraceptives that can be placed in a woman's arm.

The disks are 90 percent air, making them highly permeable to immune cells. They release cytokines, powerful attractants of immune-system messengers called dendritic cells.

These cells enter an implant's pores, where they are exposed to antigens specific to the type of tumor being targeted. The dendritic cells then report to nearby lymph nodes, where they activate the immune system's T cells to hunt down and kill tumor cells throughout the body.

"Much as an immune response to a bacterium or virus generates long-term resistance to that particular strain, we anticipate our materials will generate permanent and body-wide resistance against cancerous cells, providing durable protection against relapse," says Mooney, a core member of the recently established Wyss Institute for Biologically Inspired Engineering at Harvard.

The implants could also be loaded with bacterial or viral antigens to safeguard against an array of infectious diseases. They could even redirect the immune system to combat autoimmune diseases such as type 1 diabetes, which occurs when immune cells attack insulin-producing pancreatic cells.

"This study demonstrated a powerful new application for polymeric biomaterials that may potentially be used to treat a variety of diseases by programming or reprogramming host cells," Mooney and his co-authors write in Nature Materials. "The system may be applicable to other situations in which it is desirable to promote a destructive immune response (for example, eradicate infectious diseases) or to promote tolerance (for example, subvert autoimmune disease)."

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Scientists find new way to produce hydrogen

Scientists at Penn State University and the Virginia Commonwealth University have discovered a way to produce hydrogen by exposing selected clusters of aluminum atoms to water. The findings are important because they demonstrate that it is the geometries of these aluminum clusters, rather than solely their electronic properties, that govern the proximity of the clusters' exposed active sites. The proximity of the clusters' exposed sites plays an important role in affecting the clusters' reactions with water. The team's findings will be published in the 23 January 2009 issue of the journal Science.

"Our previous research suggested that electronic properties govern everything about these aluminum clusters, but this new study shows that it is the arrangement of atoms within the clusters that allows them to split water," said A. Welford Castleman Jr., Eberly Family Distinguished Chair in Science and Evan Pugh Professor in the Penn State Departments of Chemistry and Physics. "Generally, this knowledge might allow us to design new nanoscale catalysts by changing the arrangements of atoms in a cluster. The results could open up a new area of research, not only related to splitting water, but also to breaking the bonds of other molecules, as well."

The team, which also includes Penn State graduate students Patrick Roach and Hunter Woodward and Virginia Commonwealth University Professor of Physics Shiv Khanna and postdoctoral associate Arthur Reber, investigated the reactions of water with individual aluminum clusters by combining them under controlled conditions in a custom-designed flow-reactor. They found that a water molecule will bind between two aluminum sites in a cluster as long as one of the sites behaves like a Lewis acid, a positively charged center that wants to accept an electron, and the other behaves like a Lewis base, a negatively charged center that wants to give away an electron. The Lewis-acid aluminum binds to the oxygen in the water and the Lewis-base aluminum dissociates a hydrogen atom. If this process happens a second time with another set of two aluminum sites and a water molecule, then two hydrogen atoms are available, which then can join to become hydrogen gas (H2).

The team found that the aluminum clusters react differently when exposed to water, depending on the sizes of the clusters and their unique geometric structures. Three of the aluminum clusters produced hydrogen from water at room temperature. "The ability to produce hydrogen at room temperature is significant because it means that we did not use any heat or energy to trigger the reaction," said Khanna. "Traditional techniques for splitting water to produce hydrogen generally require a lot of energy at the time the hydrogen is generated. But our method allows us to produce hydrogen without supplying heat, connecting to a battery, or adding electricity. Once the aluminum clusters are synthesized, they can generate hydrogen on demand without the need to store it."

Khanna hopes that the team's findings will pave the way toward investigating how the aluminum clusters can be recycled for continual usage and how the conditions for the release of hydrogen can be controlled. "It looks as though we might be able to come up with ways to remove the hydroxyl group (OH-) that remains attached to the aluminum clusters after they generate hydrogen so that we can reuse the aluminum clusters again and again," he said.

The team plans to continue their research with a goal of refining their new method. This research was supported by the Air Force Office of Scientific Research.

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Tiny lasers get a notch up

<p>Tiny lasers get a notch up</p>

A new theoretical analysis could help design better microlasers

WASHINGTON, Jan. 22—Tiny disk-shaped lasers as small as a speck of dust could one day beam information through optical computers. Unfortunately, a perfect disk will spray light out, not as a beam, but in all directions. New theoretical results, reported in the Optical Society (OSA) journal Optics Letters, explain how adding a small notch to the disk edge provides a single outlet for laser light to stream out.

To increase the speed of computers and telecommunication networks, researchers are looking to replace electrical currents with beams of light that would originate from small semiconductor lasers. However, shrinking lasers down to a few micrometers in size is not easy. The typical laser builds up its concentrated light beam by bouncing light rays, or modes, back and forth inside a reflective cavity. This linear design is not practical for microlasers. Instead, scientists discovered in 1992 that they could get light amplification by having rays bounce around in a circle inside a small flat disk. These light rays are called "whispering gallery modes" because they are similar to sound waves that travel across a room by skimming along a curved wall or ceiling.

The problem is that a disk is rotationally invariant, so there is no preferred direction for the amplified light to escape. Many microlaser designs end up shooting light out in multiple directions within the plane of the disk. "The experimentalists have a holy grail of unidirectional emission in microlasers," says Martina Hentschel of the Max Planck Institute for the Physics of Complex Systems. In the past few years, some progress has been made with so-called spiral microlasers, which have a tiny notch that resembles the outer opening of a snail shell. Certain experiments have shown that light tends to propagate in a single direction from the notch. But other experiments have not been so lucky. In order to understand these contrasting results, Hentschel and her colleague Tae-Yoon Kwon have performed a systematic study of spiral microlasers using a state-of-the-art theoretical description.

Physicists typically treat the light rays trapped inside a cavity as if they were billiard balls bouncing off walls, Hentschel explains. Some light rays escape, but those rays that just barely graze the inside surface are fully reflected back into the cavity (this being the same effect that channels light beams along optical fibers). Unfortunately, this simple "billiard" model is not sufficient for explaining spiral microlasers, Hentschel says.

Hentschel and Kwon therefore chose a more sophisticated model based on the electromagnetic wave and laser equations. This framework allowed the researchers to control what part of the semiconductor material would be excited, or "pumped," to a light-emitting state. Numerical calculations showed that the two whispering gallery modes inside a spiral cavity—one traveling clockwise, the other counterclockwise—are coupled together, but only one of these modes is able to escape out through the spiral's notch. To maximize this unidirectional emission, the researchers found that the notch size should be roughly twice the wavelength of the light. Moreover, the pumping needs to be confined to the rim of the spiral, specifically the outer 10 percent. These parameters could aid in the design of better-collimated microlasers. "The optimal geometry and boundary pumping is very useful to know for an experimentalist," Hentschel says.

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UW has no right to portion of surgeon's huge royalty payments

Todd Finkelmeyer  —  1/21/2009 1:50 pm

University of Wisconsin-Madison orthopedic surgeon and researcher Dr. Thomas Zdeblick has received millions of dollars in royalty payments from a medical device company for a variety of spinal implants he helped invent, according to an investigation recently made public by Sen. Charles Grassley, R-Iowa.

But a review by The Capital Times finds that the university has no legal right to share in Zdeblick's  windfall. University policy only requires its researchers to patent inventions through the Wisconsin Alumni Research Foundation if their discoveries are funded with federal money.

"The policy at the university is you start with the presumption that faculty and staff own their own intellectual property," said Carl Gulbrandsen, managing director of WARF. "Then it becomes an issue of funding source. And if it's not federally funded research, they don't have to go through WARF. We try to be user-friendly and add value, but not everyone goes through us."

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Argonne scientists prove unconventional superconductivity in new iron arsenide compounds

Inelastic neutron scattering is sensitive to sign of superconducting gap

ARGONNE, Ill. (Jan. 9, 2009) — Scientists at U.S. Department of Energy's Argonne National Laboratory used inelastic neutron scattering to show that superconductivity in a new family of iron arsenide superconductors cannot be explained by conventional theories.


"The normal techniques for revealing unconventional superconductivity don't work with these compounds," physicist Ray Osborn said. "Inelastic neutron scattering is so far the only technique that does."

Conventional superconductivity can be explained by a theory developed by Bardeen, Cooper and Schrieffer (BCS) in 1957. In BCS theory, electrons in a superconductor combine to form pairs, called Cooper pairs, which are able to move through the crystal lattice without resistance when an electric voltage is applied. Even when the voltage is removed, the current continues to flow indefinitely, the most remarkable property of superconductivity, and one that explains the keen interest in their technological potential.

Normally, electrons repel each other because of their similar charge, but, in superconductors, they coordinate with vibrations of the crystal lattice to overcome this repulsion. But scientists don't believe the vibrational mechanism in the iron arsenides is strong enough to make them superconducting. This has led theorists to propose that this superconductivity has an unconventional mechanism, perhaps like high-temperature copper-oxide superconductors. Some iron arsenides are antiferromagnetic, rather than superconducting, so magnetism rather than atomic vibrations might provide the electron glue.

In BCS superconductors, the energy gap between the superconducting and normal electronic states is constant, but in unconventional superconductors the gap varies with the direction the electrons are moving. In some directions, the gap may be zero. The puzzle is that the gap does not seem to vary with direction in the iron arsenides. Theorists have argued that, while the size of the gap shows no directional dependence in these new compounds, the sign of the gap is opposite for different electronic states. The standard techniques to measure the gap, such as photoemission, are not sensitive to this change in sign.

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