PUBLIC RELEASE DATE:

20-Apr-2014

Contact: Craig Brierley craig.brierley@admin.cam.ac.uk 44-012-237-66205 University of Cambridge

Stem cells the body's master cells demonstrate a bizarre property never before seen at a cellular level, according to a study published today from scientists at the University of Cambridge. The property known as auxeticity is one which may have application as wide-ranging as soundproofing, super-absorbent sponges and bulletproof vests.

Most materials when stretched will contract. For example, if one pulls on an elastic band, the elastic itself will get thinner. The opposite is also true: squeeze a material and it will expand for example, if one squeezes a tennis ball between both hands, the circumference around the ball gets larger. However, material scientists have begun to explore auxeticity, an unusual property which has the opposite effect squeeze it and it will contract, stretch it and it will expand. This means that auxetic materials act as excellent shock absorbers or sponges, a fact that is being explored for various uses.

Until now, auxeticity has only been demonstrated in manmade materials and very rarely in nature, such as some species of sponge. But today, in a paper published in the journal Nature Materials, a team of University of Cambridge researchers including biologists, engineers and physicists, report having observed auxeticity in the nuclei of embryonic stem cells, master cells within the body which can turn into any other type of cell.

Dr Kevin Chalut from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, who led the study, says: "This is a pretty bizarre finding and very unexpected. When the stem cell is in the process of transforming into a particular type of cell, its nucleus takes on an auxetic property, allowing it to 'sponge up' essential materials from its surrounding. This property has not, to my knowledge, been seen before at a cellular level and is highly unusual in the natural world."

The auxetic properties only appear in the stem cell's nucleus when it is in the transition stage, changing from an embryonic, non-specific stem cell into a differentiated, tissue-specific cell, such as a heart tissue cell. Dr Chalut and colleagues treated the transitioning cell's cytoplasm, the fluid surrounding the nucleus, with a coloured dye and found that when they stretched the nucleus, it absorbed the dye, suggesting that it had expanded to become porous. It is possible that it does so to absorb molecules from the cytoplasm or environment which would help the cell differentiate.

Auxetic materials are of great interest to material scientists and engineers and this new discovery may provide clues to different methods of manufacture. The vast majority of known auxetic materials are highly ordered, such as the auxetic honeycomb. However, some examples of disordered auxetic materials are known for example, if one pulls both ends of a scrunched up ball of paper, the circumference around the ball expands. The nucleus of the transitional stem cell is likewise disordered.

"There is clearly a lot we can learn from nature," adds Dr Chalut. "We are already seeing auxeticity explored for its super-absorption properties, but despite great technological effort, auxetic materials are still rare and there is still much to discover about them in order to manufacture them better. To overcome this, materials scientists can do what has become de rigueur in their discipline: they can learn from nature. Studying how auxeticity has evolved in nature will guide research into new ways to produce auxetic materials, which might have many diverse applications in our everyday life."

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Bulletproof nuclei? Stem cells exhibit unusual absorption property

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Newswise Most drugs used to treat lung, breast and pancreatic cancers also promote drug-resistance and ultimately spur tumor growth. Researchers at the University of California, San Diego School of Medicine have discovered a molecule, or biomarker, called CD61 on the surface of drug-resistant tumors that appears responsible for inducing tumor metastasis by enhancing the stem cell-like properties of cancer cells.

The findings, published in the April 20, 2014 online issue of Nature Cell Biology, may point to new therapeutic opportunities for reversing drug resistance in a range of cancers, including those in the lung, pancreas and breast.

There are a number of drugs that patients respond to during their initial cancer treatment, but relapse occurs when cancer cells become drug-resistant, said David Cheresh, PhD, Distinguished Professor of Pathology and UC San Diego Moores Cancer Center associate director for Innovation and Industry Alliances. We looked at the cells before and after they became resistant and asked, What has changed in the cells?

Cheresh and colleagues investigated how tumor cells become resistant to drugs like erlotinib or lapatinib, known as receptor tyrosine kinase inhibitors and commonly used in standard cancer therapies. They found that as drug resistance occurs, tumor cells acquire stem cell-like properties that give them the capacity to survive throughout the body and essentially ignore the drugs.

Specifically, the scientists delineated the molecular pathway that facilitates both cancer stemness and drug resistance, and were able to identify existing drugs that exploit this pathway. These drugs not only reverse stem cell-like properties of tumors, but also appear to re-sensitize tumors to drugs that the cancer cells had developed resistance to.

The good news is that weve uncovered a previously undefined pathway that the tumor cells use to transform into cancer stem cells and that enable tumors to become resistant to commonly used cancer drugs, said Cheresh.

Based on these findings, Hatim Husain, MD, an assistant professor who treats lung and brain cancer patients at Moores Cancer Center, has designed a clinical trial to attack this pathway in patients whose tumors are drug-resistant. The trial will be open to patients with lung cancer who have experienced cancer progression and drug resistance to erlotinib. It is expected to begin in the next year.

Resistance builds to targeted therapies against cancer, and we have furthered our understanding of the mechanisms by which that happens, said Husain. Based on these research findings we now better understand how to exploit the Achilles heel of these drug-resistant tumors. Treatments will evolve into combinational therapies where one may keep the disease under control and delay resistance mechanisms from occurring for extended periods of time.

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Cancer Stem Cells Linked to Drug Resistance

Scientists have replicated one of the most significant accomplishments in stem cell research by creating human embryos that were clones of two men.

The lab-engineered embryos were harvested within days and used to create lines of infinitely reproducing embryonic stem cells, which are capable of growing into any type of human tissue.

The work, reported Thursday in the journal Cell Stem Cell, comes 11 months after researchers in Oregon said they had produced the world's first human embryo clones and used them to make stem cells. Their study, published in Cell, aroused skepticism after critics pointed out multiple errors and duplicated images.

In addition, the entire effort to clone human embryos and then dismantle them in the name of science troubles some people on moral grounds.

MORE: Medicines and machines, inspired by nature

The scientists in Oregon and the authors of the new report acknowledged that the clones they created could develop into babies if implanted in surrogate wombs. But like others in the field, they have said reproductive cloning would be unethical and irresponsible.

The process used to create cloned embryos is called somatic cell nuclear transfer, or SCNT. It involves removing the nucleus from an egg cell and replacing it with a nucleus from a cell of the person to be cloned. The same method was used to create Dolly the sheep in 1996, along with numerous animals from other species.

Human cloning was a particular challenge, in part because scientists had trouble getting enough donor eggs to carry out their experiments. Some scientists said SCNT in humans would be impossible.

Dr. Robert Lanza, the chief scientific officer for Advanced Cell Technology Inc. in Marlborough, Mass., has been working on SCNT off and on for about 15 years. He and his colleagues finally achieved success with a modified version of the recipe used by the Oregon team and skin cells donated by two men who were 35 and 75.

After swapping out the nucleus in the egg cell, both groups used caffeine to delay the onset of cell division a technique that has been called "the Starbucks effect." But instead of waiting 30 minutes to prompt cell division, as was done in the Oregon experiment, Lanza and his team waited two hours.

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Scientists use cloning to make stem cells matched to two adults