Scientists have developed safer way to alternative to embryonic stem cells

Scientists have developed what appears to be a safer way to create a promising alternative to embryonic stem cells, boosting hopes that such cells could sidestep the moral and political quagmire that has hindered the development of a new generation of cures.

The researchers 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.

"It's a leap forward in the safe application of these cells," said Andras Nagy of Mount Sinai Hospital in Toronto, who helped lead the international team of researchers that described the work in two papers being published online today by the journal Nature. "We expect this to have a massive impact on this field."

In addition to the scientific implications, the work comes at a politically sensitive moment. Scientists are anxiously waiting for President Obama to follow through on his promise to lift restrictions on federal funding for research on human embryonic stem cells. Critics of such a move immediately pointed to the work as the latest evidence that the alternative cells make such research unnecessary.

"Stem cell research that requires destroying embryos is going the way of the Model T," Richard M. Doerflinger of the U.S. Conference of Catholic Bishops said. "No administration that values science and medical progress over politics will want to divert funds now toward that increasingly obsolete and needlessly divisive approach."

Scientists, however, while praising the work as a potentially important advance, said it remains crucial to work on both types of cells because it is far from clear which will turn out to be more useful.

"The point is, we don't know yet what the end potential of either of these approaches will be," said Mark A. Kay of Stanford University. "No one has cured any disease in people with any of these approaches yet. We don't know enough yet to know which approach will be better."

Because embryonic stem cells are believed capable of becoming any kind of tissue in the body, scientists believe they could eventually lead to treatments or even cures for a host of ailments, including heart disease, diabetes, and Alzheimer's and Parkinson's diseases. In 2001, President George W. Bush restricted federal funding for human embryonic stem cell research to prevent taxpayer money from encouraging the destruction of human embryos, which is necessary to obtain the cells.

The alternative cells, known as induced pluripotent stem cells, or iPS cells, appear to have many of the same characteristics as embryonic stem cells but are produced by activating genes in adult cells to "reprogram" them into a more primitive state, bypassing the moral, political and ethical issues surrounding embryonic cells. Until now, however, their use has been limited because the genetic manipulation required the use of viruses, raising concerns the cells could cause cancer if placed in a patient. That has triggered a race to develop alternative approaches.

"These viral insertions are quite dangerous," Nagy said.

In the new work, Nagy and his colleagues in Toronto and at the University of Edinburgh in Scotland instead used a sequence of DNA known as a transposon, which can insert itself into the genetic machinery of a cell. In this case, the researchers used a transposon called "piggyBac" to carry four genes that can transform mouse and human embryonic skin cells into iPS cells. After the conversion took place, the researchers removed the added DNA from the transformed cells using a specific enzyme.

"PiggyBac carries the four genes into the cells and reprograms the cells into stem cells. After they have reprogrammed the cells, they are no longer required, and in fact they are dangerous," Nagy said. "After they do their job they can be removed seamlessly, with no trace left behind. The ability for seamless removal opens up a huge possibility."
A series of tests showed that the transformed cells had many of the properties of embryonic stem cells, Nagy said.

The researchers did their initial work on skin cells from embryos but say the approach should work just as efficiently in adult cells, and they plan to start those experiments.

"We do not expect that adult cells would behave significantly differently than the ones we are using currently," Nagy said.

In addition to producing safer cell lines that would be less likely to cause cancer in patients, the advance will enable many more scientists to begin working on such cells because they require no expertise or special laboratories necessary for working with viruses, he said.

"This opens up the possibility of working in this field for laboratories that don't have viral labs attached to them. A much larger number of laboratories will be able to push this field forward," Nagy said.

Other researchers praised the work.

"It's very significant," said George Q. Daley, a stem cell researcher at Children's Hospital in Boston. "I think it's a major step forward in realizing the value of these cells for medical research."

"It's very exciting work," agreed Robert Lanza, a stem cell researcher at Advanced Cell Technology in Worcester, Mass. "With the new work, we're only a hair's breadth away from the biggest prize in regenerative medicine -- a way to create patient-specific cells that are safe enough to use clinically."

Kay agreed that the work is promising but cautioned that much more research will be needed to prove that cells produced this way are safe. Many scientists are working on other approaches that may turn out to be safer and more efficient, he said.

"This is a step forward. The research is heading in the right direction. But there still may be room for improvement," he said.

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New Method For Creating Stem Cells
Mount Sinai Hospital's Dr. Andras Nagy discovered a new method of creating stem cells that could lead to possible cures for devastating diseases including spinal cord injury, macular degeneration, diabetes and Parkinson's disease. The study, published by Nature, accelerates stem cell technology and provides a road map for new clinical approaches to regenerative medicine.

Complicated Nano-structures Assembled With Magnets

Duke University and the University of Massachusetts have created a unique set of conditions in which tiny particles within a solution will consistently assemble themselves into these and other complex shapes.
By manipulating the magnetization of a liquid solution, the researchers have for the first time coaxed magnetic and non-magnetic materials to form intricate nano-structures. The resulting structures can be "fixed," meaning they can be permanently linked together. This raises the possibility of using these structures as basic building blocks for such diverse applications as advanced optics, cloaking devices, data storage and bioengineering.

Changing the levels of magnetization of the fluid controls how the particles are attracted to or repelled by each other. By appropriately tuning these interactions, the magnetic and non-magnetic particles form around each other much like a snowflake forms around a microscopic dust particle.

"We have demonstrated that subtle changes in the magnetization of a fluid can create an environment where a mixture of different particles will self-assemble into complex superstructures," said Randall Erb, fourth-year graduate student. He performed these experiments in conjunction with another graduate student Hui Son, in the laboratory of Benjamin Yellen, assistant professor of mechanical engineering and materials science and lead member of the research team.

The results of the Duke experiments appear in Feb. 19 issue of the journal Nature.

The nano-structures are formed inside a liquid known as a ferrofluid, which is a solution consisting of suspensions of nanoparticles composed of iron-containing compounds. One of the unique properties of these fluids is that they become highly magnetized in the presence of external magnetic fields. The unique ferrofluids used in these experiments were developed with colleagues Bappaditya Samanta and Vincent Rotello at the University of Massachusetts.

"The key to the assembly of these nano-structures is to fine-tune the interactions between positively and negatively magnetized particles," Erb said. "This is achieved through varying the concentration of ferrofluid particles in the solution. The Saturn and flower shapes are just the first published examples of a range of potential structures that can be formed using this technique."

According to Yellen, researchers have long been able to create tiny structures made up of a single particle type, but the demonstration of sophisticated structures assembling in solutions containing multiple types of particles has never before been achieved. The complexity of these nano-structures determines how they can ultimately be used.

"It appears that a rich variety of different particle structures are possible by changing the size, type and or degree of magnetism of the particles," Yellen said.

Yellen foresees the use of these nano-structures in advanced optical devices, such as sensors, where different nano-structures could be designed to possess custom-made optical properties. Yellen also envisions that rings composed of metal particles could be used for antenna designs, and perhaps as one of the key components in the construction of materials that display artificial "optical magnetism" and negative magnetic permeability.

In the Duke experiments, the nano-structures were created by applying a uniform magnetic field to a liquid containing various types of magnetic and non-magnetic colloidal particles contained between transparent glass slides to enable real-time microscopic observations of the assembly process. Because of the unique nature of this "bulk" assembly technique, Yellen believes that the process could easily be scaled up to create large quantities of custom-designed nano-structures in high-volume reaction vessels. However, the trick is to also be able to glue the structures together, because they will fall apart when the external field is turned off, he said.

"The magnetic forces assembling these particles are reversible," Yellen said. "We were able to lock these nano-structures in their intended shapes both by using chemical glues and by simple heating."

The Duke team plans to test different combinations of particles and ferrofluids developed by the University of Massachusetts team to create new types of nano-structures. They also want to try to make even smaller nano-structures to find the limitations of the assembly process, and study the interesting optical properties which are expected from these structures.



The Ethics of Nanotechnology
What kind of world do we wish to inhabit and leave for following generations? Our planet is in trouble if current trends continue into the future: environmental degradation, extinction of species, rampant diseases, chronic warfare, poverty, starvation and social injustice.

Are suffering and despair humanity's fate? Not necessarily. We have within our grasp the technology to help bring about great progress in elevating humanity. Or we can use our evolving knowledge for destructive ends. We are already immersed in fiery debates on genetic engineering, cloning, nuclear physics and the science of warfare. Nanotechnology, with its staggering implications, will create a whole new set of ethical quandaries. A strong set of operating principles is needed -- standards by which we can guide ourselves to a healthier destiny.

The following are some ethical guidelines gleaned from both Foresight and our own philosophy and experience in this field:

* Nanotechnology's highest and best use should be to create a world of abundance where no one is lacking for their basic needs. Those needs include adequate food, safe water, a clean environment, housing, medical care, education, public safety, fair labor, unrestricted travel, artistic expression and freedom from fear and oppression.

* High priority must be given to the efficient and economical global distribution of the products and services created by nanotechnology. We recognize the need for reasonable return on investment, but we must also recognize that our planet is small and we all depend upon each other for safety, stability, even survival.

* Military research and applications of nanotechnology must be limited to defense and security systems, and not for political purposes or aggression. And any government-funded research that generates useful non-military technological advances must be made available to the public.

* Scientists developing and experimenting with nanotechnology must have a solid grounding in ecology and public safety, or have someone on their team who does. Scientists and their organizations must also be held accountable for the willful, fraudulent or irresponsible misuse of the science.

* All published research and discussion of nanotechnology should be accurate as possible, adhere to the scientific method, and give due credit to sources. Labeling of products should be clear and accurate, and promotion of services, including consulting, should disclose any conflicts of interest.

* Published debates over nanotechnology, including chat room discussions, should focus on advancing the merits of the arguments rather than personal attacks, such as questioning the motives of opponents.

* Business models in the field should incorporate long-term, sustainable practices, such as the efficient use of resources, recycling of toxic materials, adequate compensation for workers and other fair labor practices.

* Industry leaders should be collaborative and self-regulating, but also support public education in the sciences and reasonable legislation to deal with legal and social issues associated with nanotechnology.

silicon chips used to repair damaged tissue in the human body.

Computer chips may 'revamp nerve

Researchers have enthused closer to creation silicon chips which could one day be used to fix damaged tissue in the human body.

Edinburgh University has developed a technique, which allows neurons to grow in fine, detailed patterns on the surface of tiny computer chips.

Neurons are the basic cells of the human nervous system.
The scientists said the development may eventually enable chips to replace damaged nerve or muscle fibres.
They also said the development could possibly be used in the development of prosthetics in the future.
During the chip manufacturing process, the scientists printed patterns on the smooth silicon surface.

The chip was then dipped in a patented mixture of proteins, and neurons grew along the patterns on the surface.
The technique also works with stem cells.
It is hoped the method will eventually enable any type of tissue to be grown on a tailor-made pathway and implanted as prosthetic tissue in the body.
Professor Alan Murray, head of Edinburgh University's School of Engineering and Electronics, who led the research, said: "This is a small but important step on the path towards the long-term goal of many scientists and medical experts - to develop surgical implants using silicon chips.
"We can now make silicon chips with circuitry as well as pathways where cells can grow in the body.
"One of the areas this could be used in is prosthetics - if we can cause cells from damaged tissues to grow where we want.
"It is going towards the realms of science fiction - there is a definite Incredible Hulk feel about it."
He added: "We also hope that, rather sooner than this, the technique will allow better methods of drug discovery and reduce the need for animal testing, as new medicines could be tested on chips rather than in live creatures."
The research was funded by the Engineering and Physical Sciences Research Council.

Victory of MS stem-cell treatment

Stem cells are showing more and more potential in the treatment of MS and the challenge we now face is proving their effectiveness in trials involving large numbers of people.

Not one of 21 adults with relapsing-remitting MS who had stem cells transplanted from their own bone marrow deteriorated over three years.
And 81% improved by at least one point on a scale of neurological disability, The Lancet Neurology reported.
Further tests are now planned, and a UK expert called the work "encouraging".
MS is an autoimmune disease which affects about 85,000 people in the UK.
It is caused by a defect in the body's immune system, which turns in on itself, causing damage to the nerves which can lead to symptoms including blurred vision, loss of balance and paralysis.

At first, the condition mostly causes intermittent symptoms that are partly reversible.
Over a 10-15 year period after onset, most patients develop secondary-progressive MS, with gradual but irreversible neurological impairment.
It is not the first time this treatment - known as autologous non-myeloablative haemopoietic stem-cell transplantation - has been tried in people with MS, but there has not been a great deal of success.
The researchers at Northwestern University School of Medicine in Chicago said most other studies had tried the transplants in people with secondary-progressive MS where the damage had already been done.
In the latest trial patients with earlier stage disease who, despite treatment had had two relapses in the past year, were offered the transplant.
Immune system
Stem cells were harvested from the patients and frozen while drugs were given to remove the immune cells or lymphocytes causing the damage.
The stem cells were then transplanted back to replenish the immune system - effectively resetting it.
Five patients in the study relapsed, but went into remission after receiving other therapy.
The researchers are now doing a randomised controlled trial in a larger number of patients to compare the treatment with standard therapy.
Study leader Professor Richard Burt said this was the first MS study of any treatment to show reversal of damage.
"You don't want to wait until the horse has left the barn before you close the barn door - you want to treat early.
"I think the reversal is the brain repairing itself.
"Once you're at the progressive stage you have exceeded the ability of the brain to repair itself," he said.
However, he cautioned that it was important to wait for the results of the larger trial.
And that he would not call it a cure but "changing the natural history of the disease".
Dr Doug Brown, research manager at the MS Society, said the results were very encouraging.
"It's exciting to see that in this trial not only is progression of disability halted, but damage appears to be reversed.
"Stem cells are showing more and more potential in the treatment of MS and the challenge we now face is proving their effectiveness in trials involving large numbers of people."