Full-sized human-like ear grown from animal tissue

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Main Category: Cosmetic Medicine / Plastic Surgery
Also Included In: Ear, Nose and Throat;  Biology / Biochemistry
Article Date: 01 Aug 2013 - 3:00 PDT Current ratings for:
Full-sized human-like ear grown from animal tissue

A team led by researchers at Massachusetts General Hospital (MGH) in Boston has engineered an artificial ear from animal structural tissue and cells. It looks and flexes like a human one and distorts only minimally during growth, thanks to the incorporation of a thin wire frame.

The researchers hope their techniques, once fine-tuned and adapted to use patients' own cells, could one day help people with missing or deformed outer ears.

They write about their work in a July 31st online issue of the Journal of the Royal Society Interface. Lead author Dr. Thomas Cervantes of the Department of Surgery at MGH told the press:

"This is the first demonstration of a full-size human ear that maintains shape and flexibility after 3 months."

Previously, the team had engineered an ear on a smaller scale, the size of a baby's, implanted on the back of a mouse.

This time they grew a full-sized adult ear, and they showed that it developed with minimal distortion when implanted on a rat.

The full-sized artificial ear contains a titanium wire frame to hold its shape, as did the earlier small one.

Appearance of the engineered ear with embedded wire framework implanted in a rat for 12 weeks (a) Before explant. (b) After explant. (c) Image of explanted engineered ear without an embedded wire framework. (d) The explanted engineered ear with wire framework maintained its shape and could be elastically deformed. Photo credit: Royal Society Publishing

The team used collagen from cows to make a 3D tissue scaffold, held in shape with the wire frame, to "maintain the gross dimensions of the engineered ear after implantation," and populated it with ear cartilage cells from sheep.

The combination of the wire frame and collagen scaffold was able to resist the forces that would otherwise deform the structure during the reconstruction processes of making new cartilage tissue and wound healing, note the authors.

An improvement on the earlier model was that they also redesigned the ear geometry to achieve "a more accurate aesthetic" shape.

After three months embedded in the backs of nude male rats, the ears containing the titanium wire support showed much less distortion of the initial ear shape than ears without the wire frame.

All the implants were well tolerated over the 12 weeks in the live rats and showed no exposure or extrusions.

But when they removed the artificial ears, the researchers found the ones without the titanium frame were flattened and lost their shape, whereas the ones containing the wire framework held their shape and also showed similar flexibility to the human ear.

To assess changes to shape over the 12 weeks, the team took CT scans of the titanium framework before and after implantation. They analyzed several measures, including overall length, width and depth, and curvature values for each section within the framework.

Using such measures, they were able to work out changes to the various dimensions and better understand the bending forces experienced by the framework.

"These quantitative shape analysis results have identified opportunities to improve shape fidelity of engineered ear constructs," they conclude.

Cervantes explains that:

"Shape and flexibility are key; tissue engineered constructs tend to distort in shape during growth, which is obviously a problem for the ear, because we are aiming to recreate a very specific shape."

He told BBC News that their study is a "significant step forward in preparing the tissue-engineered ear for human clinical trials," which he anticipates could start in about 5 years.

The study follows a succession of breakthroughs in engineered tissue.

Earlier this year, we heard how a two-year-old girl born without a windpipe received an artificial trachea grown from her own stem cells.

And another team has bioengineered an artificial ovary that makes sex hormones in the same proportions as a healthy one, offering women a more natural way of having hormone replacement therapy.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our cosmetic medicine / plastic surgery section for the latest news on this subject. "Design of composite scaffolds and three-dimensional shape analysis for tissue-engineered ear"; Thomas M. Cervantes, Erik K. Bassett, Alan Tseng, Anya Kimura, Nick Roscioli, Mark A. Randolph, Joseph P. Vacanti, Theresa A. Hadlock, Rajiv Gupta, Irina Pomerantseva, and Cathryn A. Sundback; J. R. Soc. Interface 6 October 2013 vol. 10 no. 87 20130413, published online 31 July 2013; DOI: 10.1098/rsif.2013.0413; Link to Abstract. Additional sources: The Royal Society; BBC News. Please use one of the following formats to cite this article in your essay, paper or report:

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First-ever small animal model of norovirus provides tool for future drug studies

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: GastroIntestinal / Gastroenterology
Article Date: 24 Jul 2013 - 1:00 PDT Current ratings for:
First-ever small animal model of norovirus provides tool for future drug studies

An animal model of the human norovirus created at the University of Michigan Health System lays the groundwork for understanding the biology of the pesky virus and developing antiviral drug treatment.

Well-known as the virus that impacts cruise ship vacations, norovirus leads to misery on land too. The virus spreads quickly from person to person in any closed-in space, such as schools, nursing homes, or day-care centers.

"The first virus in this group was discovered in 1972 following a disease outbreak at a school in Norwalk, Ohio in 1968. Since then research has been underway to culture noroviruses in the laboratory and develop animal models," says lead researcher Christiane Wobus, Ph.D., assistant professor in the Department of Microbiology and Immunology at the University of Michigan Medical School.

An international group of scientists from the U.S. and Germany authored the study published in mBIO, a journal of the American Society of Microbiology.

"Norovirus research has been hampered by the absence of a norovirus cell culture and a genetically manipulable small animal model," Wobus says. "This new model gives us the tool to test potential antiviral compounds and may lay the foundation to culture these viruses in the lab."

The new model was developed by determining whether human noroviruses can infect "humanized" mice, this is mice containing human immune cells. These mice are widely used for study of the human immunodeficiency virus (HIV), a virus which can only infect human cells.

As a control researchers also included the same mice without human immune cells. In the study, both groups of mice were infected by human norovirus.

Additional studies determined that the immunodeficient background of this particular mouse strain is important in permitting human norovirus infection and identified macrophages, a vital immune cell in the body, as the cell type infected by the virus.

Very few particles of the virus can lead to infection. Estimates are as few as 18 particles can cause gastroenteritis (inflammation of the stomach and intestines) and lead to diarrhea, vomiting and stomach pain. In the U.S. norovirus causes approximately 21 million cases of acute gastroenteritis a year, and 800 deaths.

"Most people can cope with the symptoms, but deaths are more likely among the elderly mainly because of dehydration," Wobus says.

Only the common cold is more widespread than the norovirus, which can remain on surfaces for weeks, ready to cause more infections. Because it lacks a lipid envelope, norovirus is not susceptible to common disinfectants and alcohol-based sanitizers.

The economic impact of these infections is staggering with an economic cost for norovirus associated food-borne outbreaks alone of $5.8 billion in the U.S.

There is no vaccine for preventing norovirus infection and no drug to treat it. But the Centers for Disease Control and Prevention offers some tips for prevention, including handwashing with soap and water, washing fruits and vegetables properly and cleaning and disinfecting surfaces, and if you are sick not preparing food or caring for others.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject.

Additional authors: Taube, S.*, Kolawole, A.O.*, Höhne, M., Wilkinson, J.E., Handley, S.A., Perry, J.W., Thackray, LB., Akkina, R. *Both authors contributed equally.

Reference: "A Mouse Model for Human Norovirus,” mBIO 4:e00450-13.

Funding: National Institutes of Health grants AI080611; AI073255; AI0544483, U54 AI057160 and AI084887.

University of Michigan Health System

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Animal Study Finds Estrogen Enables Females To Respond Better To Stress

Main Category: Anxiety / Stress
Also Included In: Women's Health / Gynecology;  Psychology / Psychiatry
Article Date: 11 Jul 2013 - 1:00 PDT Current ratings for:
Animal Study Finds Estrogen Enables Females To Respond Better To Stress

The idea that females are more resilient than males in responding to stress is a popular view, and now University at Buffalo researchers have found a scientific explanation. The paper describing their study is published online in the high-impact journal, Molecular Psychiatry.

"We have examined the molecular mechanism underlying gender-specific effects of stress," says senior author Zhen Yan, PhD, a professor in the Department of Physiology and Biophysics in the UB School of Medicine and Biomedical Sciences. "Previous studies have found that females are more resilient to chronic stress and now our research has found the reason why."

The research shows that in rats exposed to repeated episodes of stress, females respond better than males because of the protective effect of estrogen. In the UB study, young female rats exposed to one week of periodic physical restraint stress showed no impairment in their ability to remember and recognize objects they had previously been shown. In contrast, young males exposed to the same stress were impaired in their short-term memory.

An impairment in the ability to correctly remember a familiar object signifies some disturbance in the signaling ability of the glutamate receptor in the prefrontal cortex, the brain region that controls working memory, attention, decision-making, emotion and other high-level "executive" processes.

Last year, Yan and UB colleagues published in Neuron a paper showing that repeated stress results in loss of the glutamate receptor in the prefrontal cortex of young males.

The current paper shows that the glutamate receptor in the prefrontal cortex of stressed females is intact. The findings provide more support for a growing body of research demonstrating that the glutamate receptor is the molecular target of stress, which mediates the stress response. The stressors used in the experiments mimic challenging and stressful, but not dangerous, experiences that humans face, such as those causing frustration and feelings of being under pressure, Yan says.

By manipulating the amount of estrogen produced in the brain, the UB researchers were able to make the males respond to stress more like females and the females respond more like males.

"When estrogen signaling in the brains of females was blocked, stress exhibited detrimental effects on them," explains Yan. "When estrogen signaling was activated in males, the detrimental effects of stress were blocked.

"We still found the protective effect of estrogen in female rats whose ovaries were removed," says Yan. "It suggests that it might be estrogen produced in the brain that protects against the detrimental effects of stress." In the current study, Yan and her colleagues found that the enzyme aromatase, which produces estradiol, an estrogen hormone, in the brain, is responsible for female stress resilience. They found that aromatase levels are significantly higher in the prefrontal cortex of female rats.

"If we could find compounds similar to estrogen that could be administered without causing hormonal side effects, they could prove to be a very effective treatment for stress-related problems in males," she says. She notes that while stress itself is not a psychiatric disorder, it can be a trigger for the development of psychiatric disorders in vulnerable individuals.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our anxiety / stress section for the latest news on this subject.

Jing Wei, PhD, postdoctoral associate in the UB Department of Physiology and Biophysics, is first author and Eunice Y. Yuen, PhD, former research assistant professor in the same department, contributed equally. Other co-authors are Xiangning Li, PhD, postdoctoral associate, and Ping Zhong, PhD, research scientist in the same department; Ilia N. Karatsoreos of Washington State University; and Bruce S. McEwen of Rockefeller University.

The research was funded by the National Institute of Mental Health of the National Institutes of Health.

University at Buffalo

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