Editor's Choice Academic Journal Main Category: Huntingtons Disease Also Included In: Stem Cell Research Article Date: 19 Mar 2012 - 10:00 PDT

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However, according to a study published March 15 in the journal Cell Stem Cell, a special type of brain cell created from stem cells could help restore the muscle coordination deficits that are responsible for uncontrollable spasms, a characteristic of the disease. The researchers demonstrated that movement in mice with a Huntington's-like condition could be restored.

Su-Chun Zhang, a University of Wisconsin-Madison neuroscientist and the senior author of the study, said:

In the study Zhang, who is an expert in creating various types of brain cells from human embryonic or induce pluripotent stem cells, and his team focused on GABA neurons. The degradation of GABA cells causes the breakdown of a vital neural circuit and loss of motor function in individuals suffering from Huntington's disease.

According to Zhang, GABA neurons generate a vital neurotransmitter, a chemical that helps support the communication network in the brain that coordinates movement.

Zhang and his team at the UW-Madison Waisman Center, discovered how to generate large quantities of GABA neurons from human embryonic stem cells. The team's goal was to determine whether these cells would safely integrate into the brain of a mouse model of Huntington's disease.

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Huntington's Disease - Stem Cell Therapy Potential

LOS ANGELES, Calif. - The creation of California's stem cell agency in 2004 was greeted by scientists and patients as a turning point in a field mired in debates about the destruction of embryos and hampered by federal research restrictions.

The taxpayer-funded institute wielded the extraordinary power to dole out $3 billion in bond proceeds to fund embryonic stem cell work with an eye toward treatments for a host of crippling diseases. Midway through its mission, with several high-tech labs constructed, but little to show on the medicine front beyond basic research, the California Institute for Regenerative Medicine faces an uncertain future.

Is it still relevant nearly eight years later? And will it still exist when the money dries up?

The answers could depend once again on voters and whether they're willing to extend the life of the agency.

Several camps that support stem cell research think taxpayers should not pay another cent given the state's budget woes.

"It would be so wrong to ask Californians to pony up more money," said Marcy Darnovsky of the Center for Genetics and Society, a pro-stem cell research group that opposed Proposition 71, the state ballot initiative that formed CIRM.

Last December, CIRM's former chairman, Robert Klein, who used his fortune and political connections to create Prop 71, floated the possibility of another referendum.

CIRM leaders have shelved the idea of going back to voters for now, but may consider it down the road. The institute recently submitted a transition plan to Gov. Jerry Brown and the Legislature that assumes it will no longer be taxpayer-supported after the bond money runs out. CIRM is exploring creating a non-profit version of itself and tapping other players to carry on its work.

"The goal is to keep the momentum going," board Chairman Jonathan Thomas said in an interview.

So far, CIRM has spent some $1.3 billion on infrastructure and research. At the current pace, it will earmark the last grants in 2016 or 2017. Since most are multi-year awards, it is expected to stay in business until 2021.

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California's stem cell agency ponders a future without taxpayer support

14 March 2012 Last updated at 09:00 ET By Jane O'Brien BBC News, Maine

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One of Doreen Flynn's daughters, 13-year-old Jordan, says the whole transplant process scares her

A mother in the US is desperate to find bone marrow donors to save the lives of her three daughters who are critically ill from a rare blood disorder. Now, she is challenging a federal law barring her from compensating prospective donors.

Thousands of Americans who need transplants die every year because they cannot find a suitable donor, advocates say.

They propose a controversial way to encourage more people to come forward: Pay them.

"It is widening the donor pool. A lot of times employers don't pay for the time off that these donors take from work," says Doreen Flynn of Lewiston, Maine.

"So I think in those instances those people can say, 'you know I can do that,' knowing that there will be a support system for them at the end."

Ms Flynn's three daughters have a rare genetic blood disorder called Fanconi Anaemia. Their bone marrow does not make enough blood cells to keep them healthy and their only hope for survival is a transplant.

It is against US law to sell body parts - including bone marrow. But last year, Ms Flynn won a court ruling in favour of compensating donors whose blood stem cells are collected using a process called aphaeresis.

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Should it be legal to pay for bone marrow donations?

Public release date: 12-Mar-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

Researchers at the UCLA stem cell center and the departments of chemistry and biochemistry and pathology and laboratory medicine have identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs, a finding with implications for treating a host of mitochondrial diseases.

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects and aging. There currently are no methods to successfully repair or compensate for these mutations, said study co-senior author Dr. Michael Teitell, a professor of pathology and laboratory medicine and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Between 1,000 and 4,000 children per year in the United States are born with a mitochondrial disease and up to one in 4,000 children in the U.S. will develop a mitochondrial disease by the age of 10, according to Mito Action, a nonprofit organization supporting research into mitochondrial diseases. In adults, many diseases of aging have been associated with defects of mitochondrial function, including diabetes, Parkinson's disease, heart disease, stroke, Alzheimer's disease and cancer.

"I think this is a finding that could change the field," Teitell said. "We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing. Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans."

The study appears March 12, 2012 in the peer-reviewed journal Proceedings of the National Academy of Sciences.

The current study builds on previous work published in 2010 in the peer-reviewed journal Cell, in which Teitell, Carla Koehler, a professor of chemistry and biochemistry and a Broad Stem Cell Research Center scientist, and their team uncovered a role for an essential protein that acts to shuttle RNA into the mitochondria, the energy-producing "power plant" of a cell.

Mitochondria are described as cellular power plants because they generate most of the energy supply within a cell. In addition to supplying energy, mitochondria also are involved in a broad range of other cellular processes including signaling, differentiation, death, control of the cell cycle and growth.

The import of nucleus-encoded small RNAs into mitochondria is essential for the replication, transcription and translation of the mitochondrial genome, but the mechanisms that deliver RNA into mitochondria have remained poorly understood.

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Correcting human mitochondrial mutations

OKLAHOMA -- An Oklahoma House subcommittee recently approved a bill that would provide state funding for an umbilical cord blood bank. Doctors say the cord blood provides a source of stem cells without causing harm to an unborn child.

Oklahoma State Representative John Enns nearly lost his life after the Tracker he was driving rolled over, breaking his back in 3 places and leaving him paralyzed.

"Before my accident which was in 2004, I was a microbiology professor I taught about these stemcells and I taught the difference between embryonic and adult stem cells, which is huge," Enns said. "My accident happened and then I got even more involved in because this is something that may help a paralyzed person in the future with spinal cord injuries help them to actually get up and walk."

Enns now spends most his time in a wheelchair but continues to research the benefits of umbilical cord blood. He recently authored a bill that would fund a public umbilical cord blood bank for the state.

"What we will do with that is because it is pretty expensive to get it started, we will increase the amount that you pay when you get a birth certificate by $5. This will have a 5 year sunset on it which means in 5 years it will go away," Enns said.

"After the baby is delivered and the placenta is about to be thrown a way the cells can save the life of someone who has luekemia or a genetic problem where replacing their existing bone marrow is important to their cure."

OBI's president, Dr. John Armitage, says the benefits of having an umbilical cord blood bank greatly outweighs its cost..

"There is this future benefit that cant be underestimated," Armitage said. "These cells are going to eventually be used by biotechnology firms to do amazing things in terms of new tissue generation and repairing anything from hearts to any tissue in the body."

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Oklahoma bill proposes umbilical cord blood bank

A new type of stem cell-seeded patch has shown promising results in promoting healing after a heart attack, according to a study released today in the journal STEM CELLS Translational Medicine.

Durham, NC (PRWEB) March 07, 2012

Ischemic heart disease, caused by vessel blockage, is a leading cause of death in many western countries. Studies have shown the potential of stem cells in regenerating heart tissue damaged during an attack. But even as the list of candidate cells for cardiac regeneration has expanded, none has emerged as the obvious choice, possibly because several cell types are needed to regenerate both the hearts muscles and its vascular components.

Aside from the choice of the right cell source for tissue regeneration, the best way to deliver the stem cells is up for debate, too, as intravenous delivery and injections can be inefficient and possibly harmful. While embryonic stem cells have shown great promise for heart repairs due to their ability to differentiate into virtually any cell type, less than 10 percent of injected cells typically survive the engraftment and of that number generally only 2 percent actually colonize the heart.

In order for this type of treatment is to be clinically effective, researchers need to find ways to deliver large numbers of stem cells in a supportive environment that can help cells survive and differentiate.

In the current cardiopatch study, conducted by researchers from the Faculty of Medicine of the Geneva University in collaboration with colleagues at the Ecole Polytechnique Federale de Lausanne (EPFL), cardiac-committed mouse embryonic stem cell (mESC) were committed toward the cardiac fate using a protein growth factor called BMP2 and then embedded into a fibrin hydrogel that is both biocompatible and biodegradable. The cells were loaded with superparamagnetic iron oxide nanoparticles so they could be tracked using magnetic resonance imaging, which also enabled the researchers to more accurately assess regional and global heart function.

The patches were engrafted onto the hearts of laboratory rats that had induced heart attacks. Six weeks later, the hearts of the animals receiving the mESC-seeded patches showed significant improvement over those receiving patches loaded with iron oxide nanoparticles alone. The patches had degraded, the cells had colonized the infarcted tissue and new blood vessels were forming in the vicinity of the transplanted patch. Improvements reached beyond the part of the heart where the patch had been applied to manifest globally.

Marisa Jaconi, PhD, of the Geneva University Department of Pathology and Immunology, and Jeffrey Hubbell, PhD, professor of bioengineering at the EPFL, were leaders on the investigative team. Their findings could make a significant impact on how heart patients are treated in the future. Altogether our data provide evidence that stem-cell based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction, said Jaconi.

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The full article, Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats, can be accessed at: http://www.stemcellstm.com/content/early/recent.

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Stem Cell-Seeded Cardiopatch Could Deliver Results for Damaged Hearts

By Fiona Macrae

Last updated at 1:55 AM on 8th March 2012

Important breakthrough: One in ten glaucoma sufferers go blind, due to late diagnosis, drugs not working or the disease being particularly severe (file picture)

A treatment for one of the most common causes of blindness could soon be available.

British researchers have used stem cells to heal the damage caused by glaucoma.

The treatment has only been tested on rats, but scientists say it could be tested on humans by 2015 and in widespread use four years later.

At present one in ten glaucoma sufferers go blind, due to late diagnosis, drugs not working or the disease being particularly severe.

Researchers at University College London took healthy stem cells master cells capable of turning into other types of cell and widely seen as a repair kit for the body from human eyes.

They used a cocktail of chemicals to turn them into retinal ganglion cells those that die in glaucoma. They then injected these into the eyes of rats with glaucoma-like damage.

After just four weeks, the cells had connected with existing nerve cells, and the animals eyes worked 50 per cent better, the journal Stem Cells Translational Medicine reports.

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Stem cell repair kit for glaucoma could mean a treatment for the most common cause of blindness

GAYVILLE When it came to helping his brother, Jason Selchert was willing to do a lot more than give the shirt off his back. In January, he became a bone marrow donor for his sibling, Jeff Selchert.

Jason, 39, superintendent of the Gayville-Volin School, said he had plenty of time to prepare for the procedure.

A little over two years ago, my brother, who is four years older than I am, was diagnosed with leukemia, he stated. When he was diagnosed, they determined that probably at some point in his illness, he was going to have to undergo a bone marrow transplant. Luckily enough, he has five siblings, and we were all tested. Two of the five were a match. I was one of the two.

Since the chance that a sibling will be a match is about one in four, the fact that two were a match was fortuitous, Jason said.

Jason and his oldest brother were both perfect matches, according to the blood and DNA testing.

However, Jason was selected as the best candidate.

After undergoing treatment following the initial diagnosis, Jeffs leukemia went into remission. But a few days prior to last Thanksgiving, the cancer had returned.

It was pretty well advanced, and they determined that the only way to treat it was going to be a transplant, Jason said. I had known for more than two years that it was maybe going to be an option. Its a pretty lengthy psychological process you go through to make sure that you are mentally stable enough to go through it, and understand what is going to happen and what could be the end result for me and my brother.

Jason donated his bone marrow stem cells Jan. 30. A successful transplant to his brother occurred the next day.

The worst part of the process was the time leading up to the donation, according to Jason. During the four previous days, he was given medication that caused his body to overproduce bone marrow stem cells. The process made Jason ache and feel nauseated, similar to the flu.

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Selchert Undergoes Transplant For Brother

ScienceDaily (Mar. 6, 2012) Northwestern University scientists have developed a powerful analytical method that they have used to direct stem cell differentiation. Out of millions of possibilities, they rapidly identified the chemical and physical structures that can cue stem cells to become osteocytes, cells found in mature bone.

Researchers can use the method, called nanocombinatorics, to build enormous libraries of physical structures varying in size from a few nanometers to many micrometers for addressing problems within and outside biology.

Those in the fields of chemistry, materials engineering and nanotechnology could use this invaluable tool to assess which chemical and physical structures -- including size, shape and composition -- work best for a desired process or function.

Nanocombinatorics holds promise for screening catalysts for energy conversion, understanding properties conferred by nanostructures, identifying active molecules for drug discovery or even optimizing materials for tissue regeneration, among other applications.

Details of the method and proof of concept is published in the Proceedings of the National Academy of Sciences.

"With further development, researchers might be able to use this approach to prepare cells of any lineage on command," said Chad A. Mirkin, who led the work. "Insight into such a process is important for understanding cancer development and for developing novel cancer treatment methodologies."

Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwestern's International Institute for Nanotechnology (IIN).

The new analytical method utilizes a technique invented at Northwestern called polymer pen lithography, where basically a rubber stamp having as many as 11 million sharp pyramids is mounted on a transparent glass backing and precisely controlled by an atomic force microscope to generate desired patterns on a surface. Each pyramid -- a polymeric pen -- is coated with molecules for a particular purpose.

In this work, the researchers used molecules that bind proteins found in the natural cell environment, such as fibronectin, which could then be attached onto a substrate in various patterns. (Fibronectin is a protein that mediates cell adhesion.) The team rapidly prepared millions of textured features over a large area, which they call a library. The library consisted of approximately 10,000 fibronectin patterns having as many as 25 million features ranging in size from a couple hundred nanometers to several micrometers.

To make these surfaces, they intentionally tilt the stamp and its array of pens as the stamp is brought down onto the substrate, each pen delivering a spot of molecules that could then bind fibronectin. The tilt results in different amounts of pressure on the polymeric pens, which dictates the feature size of each spot. Because the pressure varies across a broad range, so does the feature size.

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Influencing stem cell fate: New screening method helps scientists identify key information rapidly

ScienceDaily (Mar. 1, 2012) UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individual's lifetime.

The placental niche, a stem cell "safe zone," supports blood stem cell generation and expansion without promoting differentiation into mature blood cells, allowing the establishment of a pool of precursor cells that provide blood cells for later fetal and post-natal life, said study senior author Dr. Hanna Mikkola, an associate professor of molecular cell and developmental biology and a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Mikkola and her team found that PDGF-B signaling in trophoblasts, specialized cells of the placenta that facilitate embryo implantation and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique microenvironment needed for the blood precursors. When PDGF-B signaling is halted, the blood precursors differentiate prematurely, creating red blood cells in the placenta, Mikkola said.

The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.

"We had previously discovered that the placenta provides a home for a large supply of blood stem cells that are maintained in an undifferentiated state. We now found that, by switching off one signaling pathway, the blood precursors in the placenta start to differentiate into red blood cells," Mikkola said. "We learned that the trophoblasts act as powerful signaling centers that govern the niche safe zone."

The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.

"When PDGF-B signaling is lost, excessive amounts of EPO are produced in the placenta, which triggers differentiation of red blood cells in the placental vasculature," said Akanksha Chhabra, study first author and a post-doctoral fellow in Mikkola's lab.

Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.

"The idea was, if we mess up the home where the blood stem cells live, how do these cells respond to the altered environment," Chhabra said. "We found that it was important to suppress EPO where blood stem cell expansion is desired and to restrict its expression to areas where red blood cell differentiation should occur."

The finding, Chhabra said, was exciting in that one single molecular change "was enough to change the function of an important blood stem cell niche."

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Cell and signaling pathway that regulates the placental blood stem cell niche identified

London, Feb 29 (IANS) Children shot with their own stem cells, for the very first time in a rare immune disorder, have shown improvement.

The condition, known as X-CGD, is caused by faulty genes. Doctors were able to take a sample of the children's stem cells, manipulate them in the lab and reintroduce them. This gave the children a working copy of the faulty gene and their condition improved, enabling them to temporarily fight off infections.

It is the third immune disorder that doctors at Great Ormond Street Hospital have successfully tackled. The others were the life-threatening conditions, X-SCID and ada-SCID, and 90 percent of treated children have improved, with some showing signs that their immune system has been normalised for good.

Remy Helbawi, 16, from South London, was the first child with X-CGD to be treated. The condition only affects boys and means that while his body produces the white blood cells to fight viruses it does not have the correct cells to fight off bacterial or fungal infections, The Telegraph reports.

The resulting infections can be life-threatening. Up until now the only treatment has been a bone marrow transplant which would offer a permanent cure.

Remy's brother who also had the disease was found a bone marrow match and was successfully treated that way but no match has been found for Remy and a serious lung infection was threatening his life.

Remy said: "Until I was 10 I had the same life as anyone else, except I had eczema a lot of the time. I didn't have a fungal infection until about ten, but when I got my first fungal infection my life changed. I missed a lot of school, I had lots of tests and was in hospital. I would get exhausted after climbing stairs."

Before undergoing the gene therapy, Remy had to have chemotherapy which made his hair fall out and he was kept in isolation for a month.

Remy's nurse Helen Braggins said: "Remy had been unwell for last two years and began to miss school. He had significant fungal lung disease in January of last year, which was getting worse. Without some radical treatment intervention, Remy would not have survived and was becoming increasingly short of breath."

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Children improve in rare disorder with own stem cells

SILVER SPRING, Md.--(BUSINESS WIRE)--

Nuvilex, Inc. (OTCQB:NVLX), an emerging biotechnology provider of cell and gene therapy solutions, announced today Goldman Small Cap Research has reissued its buy recommendation on Nuvilex with a short term price target of $0.50 per share.

According to the research report prepared by Goldman, The current share price represents but a fraction of its true value, in our view. With recently increased interest and valuation in the pancreatic cancer treatment arena, we believe that Nuvilex is worth $0.20 just on the oncology therapies alone and that the shares will reach $0.50 in the next six months. Looking ahead, as milestone events occur, $1.00 per share is within reach over the next 12-18 months.

Goldman bases this value projection, in part, on the pending acquisition of SG Austria assets, and with it complete control over the cell encapsulation technology that forms the backbone of Nuvilexs planned biotechnology development. The report states in part the following:

Following execution of the SG Austria asset acquisition, we expect to see a flurry of events and progress on the development side which will serve as catalysts, including when management submits its protocol for the next stage pancreatic cancer trial. We would not be surprised to see the stock break through the $0.50 price on such news as well as progress on the next stage of trials for other therapies.

One reason we are so convinced of the great buying opportunity is the fact that pancreatic cancer treatments are currently at the forefront of the biotech space and are enjoying very high valuations. Although Nuvilex is a not a drug producer, but an existing therapy enhancer through the use of its live cell encapsulation enhancement platform, the timing of these milestone events could not be better for Nuvilex and a re-valuation of its offering.

The Goldman report also compares alternative oncology therapies, including Gemzar from Threshold Pharmaceuticals and Merrimack Pharmaceuticals drug encapsulation technology, noting that, contrary to these treatments, the Nuvilex live-cell encapsulation technology is not limited to one specific use, but can be adapted to use for a host of cell types. The report states, Its difficult to compare apples-to-apples in this space as Nuvilex is the only firm utilizing live-cell encapsulation therapy for cancer, while all the other treatments are based upon a particular drug usage. Contrasting the results of different Phase II clinical trials, the Goldman report comments that the pancreatic cancer therapy, based on completed Phase 1/2 data, appears to have yielded statistically greater results than competing technologies.

Commenting on The Goldman Report, Nuvilex Chief Executive Officer, Dr. Robert Ryan, stated, The report did an excellent job highlighting the value and capabilities of our cell encapsulation technology, not just for cancer therapy, but also for the vast array of treatments where live-cell encapsulation can aid multiple diseases. In the case of the completed cancer trials, it generated superior results with lower drug dosages, and reduced chemotherapeutic side effects. As we move forward with diabetes and stem cell therapy treatments, we are confident our success will, as Goldman predicts prompt leaders in multiple treatment segments to partner with Nuvilex in order to maintain their respective market shares.

Investors are recommended to study the Goldman Research Report for a detailed review and valuation methodology regarding Nuvilex.

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Nuvilex Reveals Goldman Small Cap Research Cites Groundbreaking Cancer Therapy in Updating Buy Recommendation

28-02-2012 14:48 Albert Rodriguez, MD administers stem cell therapy for Hereditary Spastic Paraplegia. stemcelldrR.com, email airpainmd@aol.com

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Stem Cell Therapy Procedure and Outcome - Video

February 27, 2012

Japanese scientists have recently discovered that hydrogen sulfide (H2S) – the chemical responsible for such malodorous phenomena as human flatulence, bad breath and rotten eggs – can be used to efficiently convert stem cells from human teeth into liver cells.

While the fetid chemical compound is produced in small quantities by the human body for use in a variety of biological signaling mechanisms, at high concentrations it is highly poisonous and extremely flammable.

A team of researchers at the Nippon Dental University in Tokyo collected stem cells from the teeth of patients undergoing extractions. The cells were harvested from the central part of the tooth known as the pulp which is made up predominantly of connective tissue and cells.

Stem cells recovered from the pulp were then divided into two groups and incubated in sealed chambers, one filled with hydrogen sulfide and the other a control group.

The cells from each chamber were then examined at three-day intervals to look for signs of transformation into liver cells. One such indicator is the ability to store glycogen, a compound that can be converted to glucose when the body needs energy.

According to a report of their findings that appeared this week in the Journal of Breath Research, the team was able to convert the stem cells to liver cells in relatively high numbers. And what’s more, said the team, H2S appears to help produce comparatively high quality, functional liver cells.

Lead researcher Ken Yaegaki explained that “[h]igh purity means there are less ‘wrong cells’ that are being differentiated to other tissues, or remaining as stem cells … These facts suggest that patients undergoing transplantation with the hepatic cells may have almost no possibility of developing teratomas (malignant tumors) or cancers.”

For the thousands of people around the world with chronic liver disease, this is a most welcome discovery, one that Yaegaki believes could potentially revolutionize this field of medicine.

“Until now, nobody has produced the protocol to regenerate such a huge number of hepatic cells for human transplantation,” added Yaegaki.

“Compared to the traditional method or suing fetal bovine serum to produce the cells, our method is productive and, most importantly, safe.”

Yaegaki’s hope is that his team’s discovery may eventually be fine-tuned to allow scientists to produce ample liver cells in a lab for use in repairing liver damage in human patients.

Moreover, this and similar studies in recent years have also gotten researchers in other fields questioning the possibilities for using hydrogen sulfide with other types of stem cells.

A team of researchers in China, for instance, recently reported using H2S to increase the survival rate of mesenchymal stem cells extracted from the bone marrow of rats.

—

On the Net:

Source: RedOrbit Staff & Wire Reports

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Researchers Use Noxious Gas To Convert Stem Cells To Liver Cells

For 60 years, doctors have believed women were born with all the eggs they'll ever have. Now Harvard scientists are challenging that dogma, saying they've discovered the ovaries of young women harbour very rare stem cells capable of producing new eggs.

If the report is confirmed, harnessing those stem cells might one day lead to better treatments for women left infertile because of disease — or simply because they're getting older.

"Our current views of ovarian aging are incomplete. There's much more to the story than simply the trickling away of a fixed pool of eggs," said lead researcher Jonathan Tilly of Harvard's Massachusetts General Hospital, who has long hunted these cells in a series of controversial studies.

Tilly's previous work drew fierce skepticism, and independent experts urged caution about the latest findings.

A key next step is to see whether other laboratories can verify the work. If so, then it would take years of additional research to learn how to use the cells, said Teresa Woodruff, fertility preservation chief at Northwestern University's Feinberg School of Medicine.

Still, even a leading critic said such research may help dispel some of the enduring mystery surrounding how human eggs are born and mature.

"This is going to spark renewed interest, and more than anything else it's giving us some new directions to work in," said David Albertini, director of the University of Kansas' Center for Reproductive Sciences. While he has plenty of questions about the latest work, "I'm less skeptical," he said.

Scientists have long taught that all female mammals are born with a finite supply of egg cells, called ooctyes, that runs out in middle age. Tilly, Mass General's reproductive biology director, first challenged that notion in 2004, reporting that the ovaries of adult mice harbour some egg-producing stem cells. Recently, Tilly noted, a lab in China and another in the U.S. also have reported finding those rare cells in mice.

But do they exist in women? Enter the new work, reported Sunday in the journal Nature Medicine.

First Tilly had to find healthy human ovaries to study. He collaborated with scientists at Japan's Saitama Medical University, who were freezing ovaries donated for research by healthy 20-somethings who underwent a sex-change operation.

Egg quality questions

Tilly also had to address a criticism: How to tell if he was finding true stem cells or just very immature eggs. His team latched onto a protein believed to sit on the surface of only those purported stem cells and fished them out. To track what happened next, the researchers inserted a gene that makes some jellyfish glow green into those cells. If the cells made eggs, those would glow, too.

"Bang, it worked — cells popped right out" of the human tissue, Tilly said.

Researchers watched through a microscope as new eggs grew in a lab dish. Then came the pivotal experiment: They injected the stem cells into pieces of human ovary. They transplanted the human tissue under the skin of mice, to provide it a nourishing blood supply.

Within two weeks, they reported telltale green-tinged egg cells forming.

That's still a long way from showing they'll mature into usable, quality eggs, Albertini said.

And more work is needed to tell exactly what these cells are, cautioned reproductive biologist Kyle Orwig of the University of Pittsburgh Medical Center, who has watched Tilly's work with great interest.

But if they're really competent stem cells, Orwig asked, then why would women undergo menopause? Indeed, something so rare wouldn't contribute much to a woman's natural reproductive capacity, added Northwestern's Woodruff.

Tilly argues that using stem cells to grow eggs in lab dishes might one day help preserve cancer patients' fertility. Today, Woodruff's lab and others freeze pieces of girls' ovaries before they undergo fertility-destroying chemotherapy or radiation. They're studying how to coax the immature eggs inside to mature so they could be used for in vitro fertilization years later when the girls are grown. If that eventually works, Tilly says stem cells might offer a better egg supply.

Further down the road, he wonders if it also might be possible to recharge an aging woman's ovaries.

The new research was funded largely by the U.S. National Institutes of Health. Tilly co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments.

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Egg-producing stem cells found in women's ovaries

Public release date: 26-Feb-2012
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital

For the first time, Massachusetts General Hospital (MGH) researchers have isolated egg-producing stem cells from the ovaries of reproductive age women and shown these cells can produce what appear to be normal egg cells or oocytes. In the March issue of Nature Medicine, the team from the Vincent Center for Reproductive Biology at MGH reports the latest follow-up study to their now-landmark 2004 Nature paper that first suggested female mammals continue producing egg cells into adulthood.

"The primary objective of the current study was to prove that oocyte-producing stem cells do in fact exist in the ovaries of women during reproductive life, which we feel this study demonstrates very clearly," says Jonathan Tilly, PhD, director of the Vincent Center for Reproductive Biology in the MGH Vincent Department of Obstetrics and Gynecology, who led the study. "The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure."

The 2004 report from Tilly's team challenged the fundamental belief, held since the 1950s, that female mammals are born with a finite supply of eggs that is depleted throughout life and exhausted at menopause. That paper and a 2005 follow-up published in Cell showing that bone marrow or blood cell transplants could restore oocyte production in adult female mice after fertility-destroying chemotherapy were controversial; but in the intervening years, several studies from the MGH-Vincent group and other researchers around the world have supported Tilly's work and conclusions.

These supporting studies include a 2007 Journal of Clinical Oncology report from the MGH-Vincent team that showed female mice receiving bone marrow transplants after oocyte-destroying chemotherapy were able to have successful pregnancies, delivering pups that were their genetic offspring and not of the marrow donors. A 2009 study from a team at Shanghai Jiao Tong University in China, published in Nature Cell Biology, not only isolated and cultured oocyte-producing stem cells (OSCs) from adult mice but also showed that those OSCs, after transplantation into the ovaries of chemotherapy-treated female mice, gave rise to mature oocytes that were ovulated, fertilized and developed into healthy offspring.

"That study singlehandedly deflated many of the arguments from critics of our earlier Nature paper by showing that oocyte-producing stem cells exist in mice and could develop into fully functional eggs," says Tilly. Another paper from a west-coast biotechnology company, published in Differentiation in 2010, provided further independent confirmation of Tilly's earlier conclusions regarding the presence of oocyte-producing stem cells in ovaries of adult mice.

Tilly is quick to point out, however, "These follow-up studies, while providing definitive evidence that oocyte-producing stem cells exist in ovaries of adult female mammals, were not without their limitations, leaving the question open in some scientific circles of whether the adult oocyte pool can be renewed. For example, the protocol used to isolate OSCs in the 2009 Nature Cell Biology study is a relatively crude approach that often results in the contamination of desired cells by other cell types." To address this, the MGH-Vincent team developed and validated a much more precise cell-sorting technique to isolate OSCs without contamination from other cells.

The 2009 study from China also had isolated OSCs based on cell-surface expression of a marker protein called Ddx4 or Mvh, which previously had been found only in the cytoplasm of oocytes. This apparent contradiction with earlier studies raised concerns over the validity of the protocol. Using their state-of-the-art fluorescence-activated cell sorting techniques, the MGH-Vincent team verified that, while the marker protein Ddx4 was indeed located inside oocytes, it was expressed on the surface of a rare and distinct population of ovarian cells identified by numerous genetic markers and functional tests as OSCs.

To examine the functional capabilities of the cells isolated with their new protocol, the investigators injected green fluorescent protein (GFP)-labeled mouse OSCs into the ovaries of normal adult mice. Several months later, examination of the recipient mouse ovaries revealed follicles containing oocytes with and without the marker protein. GFP-labeled and unlabeled oocytes also were found in cell clusters flushed from the animals' oviducts after induced ovulation. The GFP-labeled mouse eggs retrieved from the oviducts were successfully fertilized in vitro and produced embryos that progressed to the hatching blastocyst stage, a sign of normal developmental potential. Additionally, although the Chinese team had transplanted OSCs into ovaries of mice previously treated with chemotherapy, the MGH-Vincent team showed that it was not necessary to damage the recipient mouse ovaries with toxic drugs before introducing OSCs.

In their last two experiments, which Tilly considers to be the most groundbreaking, the MGH-Vincent team used their new cell-sorting techniques to isolate potential OSCs from adult human ovaries. The cells obtained shared all of the genetic and growth properties of the equivalent cells isolated from adult mouse ovaries, and like mouse OSCs, were able to spontaneously form cells with characteristic features of oocytes. Not only did these oocytes formed in culture dishes have the physical appearance and gene expression patterns of oocytes seen in human ovaries ? as was the case in parallel mouse experiments ? but some of these in-vitro-formed cells had only half of the genetic material normally found in all other cells of the body. That observation indicates that these oocytes had progressed through meiosis, a cell-division process unique to the formation of mature eggs and sperm.

The researchers next injected GFP-labeled human OSCs into biopsied human ovarian tissue that was then grafted beneath the skin of immune-system-deficient mice. Examination of the human tissue grafts 7 to 14 days later revealed immature human follicles with GFP-negative oocytes, probably present in the human tissue before OSC injection and grafting, as well as numerous immature human follicles with GFP-positive oocytes that would have originated from the injected human OSCs.

"These experiments provide pivotal proof-of-concept that human OSCs reintroduced into adult human ovarian tissue performed their expected function of generating new oocytes that become enclosed by host cells to form new follicles," says Tilly, a professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School and chief of Research at the MGH Vincent Department of Obstetrics and Gynecology. "These outcomes are exactly what we see if we perform the same experiments using GFP-expressing mouse OSCs, and GFP-expressing mouse oocytes formed that way go on to develop into fully functional eggs.

"In this paper we provide the three key pieces of evidence requested by those who have been skeptical of our previous work," he adds. "We developed and extensively validated a cell-sorting protocol to reliably purify OSCs from adult mammalian ovaries, proving once again that these very special cells exist. We tested the function of mouse oocytes produced by these OSCs and showed that they can be fertilized to produce healthy embryos. And we identified and characterized an equivalent population of oocyte-producing stem cells isolated from adult human ovaries."

Among the many potential clinical applications for these findings that Tilly's team is currently exploring are the establishment of human OSC banks ? since these cells, unlike human oocytes, can be frozen and thawed without damage ? the identification of hormones and factors that accelerate the formation of oocytes from human OSCs, the development of mature human oocytes from OSCs for in vitro fertilization, and other approaches to improve the outcomes of IVF and other infertility treatments.

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Tilly notes that an essential part of his group's accomplishment was collaboration with study co-author Yasushi Takai, MD, PhD, a former MGH research fellow on Tilly's team and now a faculty member at Saitama Medical University in Japan. Working with his clinical colleagues at Saitama, Takai was able to provide healthy ovarian tissue from consenting patients undergoing sex reassignment surgery, many in their 20s and early 30s. Co-lead authors of the Nature Medicine report are Yvonne White, PhD, and Dori Woods, PhD, of the Vincent Center for Reproductive Biology at MGH. Additional co-authors are Osamu Ishihara, MD, PhD, and Hiroyuki Seki, MD, PhD, of Saitama Medical University.

The study was supported by a 10-year MERIT Award to Tilly from the National Institute on Aging, a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, and Vincent Memorial Hospital Research Funds. Tilly is a co-founder of OvaScience, Inc. (www.ovascience.com), which has licensed the commercial potential of these and other patent-protected findings of the MGH-Vincent team for development of new fertility-enhancing procedures.

Massachusetts General Hospital (www.massgeneral.org), founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

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Mass. General researchers isolate egg-producing stem cells from adult human ovaries

Breakthrough stem cell research at Scripps Research Institute in La Jolla, Calif. has the potential to revive endangered species. Researchers at the Center for Regenerative Medicine are aiming to turn stem cells into gametes. Once new eggs and sperm are created, “test tube babies” can be born, possibly preserving a species.

In 1972, researchers preserved skin cells of certain endangered species at the Frozen Zoo, hoping that future technology would help to revive populations, and today Scripps researchers are combining the frozen skin cells with human stem cells to generate stem cells specific to the animal. Stem cells are turned into gametes through re-programming, a process in which retroviruses are used to bring the cells back to earlier stages of development. Last month, scientists created mouse sperm cells through this process.

Scientists view this method of species preservation as a last resort when cheaper, simpler means have failed. For instance, the white rhino, whose population is numbered at seven in the world, would benefit immensely since other methods of trying to save the species have failed. Scientists also hope to help the drill, a West African primate threatened by hunting and habitat degradation.

—compiled by Michelle Lim

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Bar Harbor – Yijun Ruan, Ph.D., an American geneticist who has pioneered new techniques to sequence and map DNA to better understand cancer growth and stem cell properties, will be the first scientist to join the new Jackson Laboratory for Genomic Medicine (JAX Genomic Medicine) in Farmington, Conn.

Ruan is currently associate director and senior group leader at the Genome Institute of Singapore and professor of biochemistry at the National University of Singapore. He is also an investigator with the Encyclopedia of DNA Elements (ENCODE) project, an international consortium of research groups funded by the National Human Genome Research Institute.
Ruan said he was attracted by The Jackson Laboratory’s famously collaborative research environment, and plans to “take a community approach to tackle genomic questions through intensive collaboration.” Through innovating new technologies and studying how the human and mouse genomes are regulated, he said his goal is to translate research findings into personalized medicine. Ruan has also been appointed director of JAX Genomic Sciences, and will be bringing his current research program and team with him to JAX Genomic Medicine.
JAX Genomic Medicine will unite doctors, patients, scientists and industry to find new ways to tailor disease diagnosis, prevention and treatment to each person’s unique genetic makeup, or genome. Ruan and other recruits will begin initial operations this year in leased space while a 173,000-square-foot permanent facility is designed and built. Construction will begin in 2013, and the new facility will open in 2014.
“Yijun’s broad interests in genome biology, coupled with his innovative approach to developing new research techniques, make him an ideal member of the new JAX Genomic Medicine research team,” said Bob Braun, Ph.D., Jackson’s associate director and chair of research.
After earning BS and MS degrees in microbiology from Huazhong Agricultural University in Wuhan, China, Ruan obtained his Ph.D. in plant molecular biology from the University of Maryland, College Park, where he also conducted postgraduate research. Following scientific appointments at Monsanto Co. in St. Louis and Large Scale Biology Corp. in Vacaville, Calif., Ruan was recruited to the Genome Institute of Singapore (GIS) in 2002. Edison Liu, M.D., former director of GIS and now president and CEO of The Jackson Laboratory, credits Ruan for building the institute’s state-of-the-art genomic technology platforms and its award-winning genome biology programs.
Ruan is an author of 70 research papers and holds patents in Japan, Singapore and the United Kingdom for the DNA analysis techniques he helped to develop. A U.S. citizen, Ruan is married and has two children.
In addition to recruiting research faculty, JAX Genomic Medicine is currently hiring a site director, science coordinator, senior human resources manager, facilities manager and senior financial analyst in Connecticut. Job announcements are on The Jackson Laboratory’s website at http://www.jax.org/careers/connecticut.html.
Braun notes that The Jackson Laboratory is expanding the research faculty at its headquarters campus in Bar Harbor, Maine, as well as recruiting faculty in Connecticut.
The Jackson Laboratory is an independent, nonprofit biomedical research institution and National Cancer Institute-designated Cancer Center based in Bar Harbor, Maine, with a facility in Sacramento, Calif., afuture institute in Farmington, Conn., and a total staff of about 1,400. Its mission is to discover the genetic basis for preventing, treating and curing human disease, and to enable research and education for the global biomedical community.

For more health news, pick up a copy of the Mount Desert Islander.

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First researcher joins The Jackson Lab for Genomic Medicine in Conn.

Newswise — The International Society for Stem Cell Research (ISSCR) is pleased to announce the winner of the 2012 McEwen Award for Innovation, a coveted prize in the field of stem cell research and regenerative medicine. The 2012 recipient is Rudolf Jaenisch, MD, Founding Member of the Whitehead Institute for Biomedical Research and Professor of Biology at the Massachusetts Institute of Technology in recognition of his pioneering discoveries in the areas of genetic and epigenetic control of development in mice that directly impact the future potential of embryonic stem cells and induced pluripotent stem cells for therapeutic utility.

The McEwen Award for Innovation is supported by the McEwen Centre for Regenerative Medicine in Toronto, Ontario, Canada. The $100,000 award honors original thinking and groundbreaking research pertaining to stem cells or regenerative medicine that opens new avenues of exploration towards the understanding or treatment of human disease or affliction.

“Rudolf Jaenisch has consistently contributed new and groundbreaking discoveries to stem cell biology and regenerative medicines that have changed the way stem cell research is conducted, said Fred H. Gage, PhD, ISSCR President. “Importantly, Rudolf not only has an uncanny sense of the next big question, but also conducts his experiments with such thoughtful and critical experimental design that his results have an immediate impact. This critical attention to detail and experimental design has greatly benefited the many gifted students that have passed through his lab and now populate many of the major stem cell centers throughout the world. Rudolf is very deserving of this award.”

Winner of the inaugural McEwen Award for Innovation in 2011, Shinya Yamanaka, MD, PhD, ISSCR President-Elect agrees. “Dr. Rudolf Jaenisch has always been on the cutting-edge of our field and his research has been a source of inspiration not only for myself, but has influenced the careers of some of our most esteemed colleagues.”

Dr. Jaenisch will be presented with the award at the ISSCR 10th Annual Meeting, in Yokohama, Japan, on Wednesday, June 13, 2012.
***
The International Society for Stem Cell Research is an independent, nonprofit membership organization established to promote and foster the exchange and dissemination of information and ideas relating to stem cells, to encourage the general field of research involving stem cells and to promote professional and public education in all areas of stem cell research and application.

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ISSCR Honors Stem Cell Research Pioneer with Prestigious McEwen Award for Innovation

An important new study by a team of scientists at RhinoCyte™ Inc., Louisville, Ky., details promising results on the effectiveness of olfactory (nasal) stem cells in repairing spinal cord damage resulting from the most common cause of these injuries — contusions (bruising) due to major trauma such as is seen in auto accidents, falls or combat. This could have major implication for the estimated 5 million people worldwide affected by spinal cord injuries – 1.275 million of them in the United States alone, where the cost of treatment exceeds $40.5 billion each year.

Louisville, Kentucky (PRWEB) February 22, 2012

An important new study released by a team of scientists at RhinoCyte™ Inc., Louisville, Ky., details promising results on the effectiveness of olfactory (nasal) stem cells in repairing spinal cord damage resulting from the most common cause of these injuries — contusions (bruising) due to major trauma. Their study is featured in the current issue of the Journal of Neurodegeneration and Regeneration.

The study, led by Dr. Fred Roisen, has great implication for the estimated 5 million people worldwide affected by spinal cord injuries – 1.275 million of them in the United States alone, where the cost of treatment exceeds $40.5 billion each year. Current treatment options are limited to retaining and retraining mobility; no drug therapies are available, but studies pertaining to stem cell treatments are showing great promise for these as well as other neurodegenerative conditions.

A previous study by the group made national headlines when lab rats whose spinal cords had been partially cut in the region of the animal’s neck in a way that disabled their front right paws were able to regain significant use of their paws after being injected with olfactory stem cells. The investigative team took the cells from the olfactory neurosensory epithelium — the part of the nose that controls the sense of smell — in adult volunteer donors who were already undergoing elective sinus surgery. The removal of the stem cells has no effect on the patients’ ability to smell. Also, the minimally invasive surgery is frequently done on an outpatient basis so the cells are readily available and, as such, are a potentially promising source of therapeutic stem cells.

The researchers isolated the stem cells and increased their numbers in the laboratory by growing them in an enriched solution. The cells were then injected into a group of lab rats. Twelve weeks later, these animals had regained control of their affected paws while a control group that received no cells had not.

This latest study continued that original work, by concentrating on contusions caused by blunt force trauma such as that resulting from an automobile accident or a fall. Spinal cord and head trauma are common among soldiers suffering serious combat injuries, too.

Two independent sets of experiments were conducted, beginning two weeks after the rats had received contusions administered in a computer-controlled surgery. In the first group, 27 out of 41 rats were injected with olfactory stem cells, while the remainder received none. In the second group, 16 rats were treated with olfactory stem cells, 11 received no treatment and 10 received stem cells grown from human skin to see how the olfactory cells compared with another stem cell source.

The results once again showed great promise, with 40 percent of the rats treated with the olfactory-derived stem cells showing significant improvement after just six weeks, compared to 30 percent of those treated with human skin-derived cells and only 9 percent of those receiving no treatment. In addition, the olfactory stem cell-treated rats showing the highest rate of improvement recovered much faster than the other groups.

“This is very exciting on numerous levels,” said Dr. Roisen. “As an autologous cell source — that is, the patient is both the donor and the recipient — olfactory stem cells bypass the time a patient must wait while a suitable donor is found, which can be critical to the outcome of the patient’s treatment. They also eliminate the need for immunosuppressive drugs, which have numerous negative side effects.

“And just as importantly, stem cells taken from the nose of an adult do away with the ethical concerns associated with using embryonic stem cells.”

The researchers are in the final stages of their enabling studies, which are scheduled to be completed by summer; Phase 1 safety studies could begin as soon as early next year.

Dr. Roisen is chief science officer and co-founder of RhinoCtye™, and a professor and chair of the University of Louisville School of Medicine’s Department of Anatomical Sciences and Neurobiology. The original work forming the basis for the contusion study was conducted by Dr. Roisen’s group at UofL and has been licensed to RhinoCtye™ (http://www.rhinocyte.com), a company he co-founded in 2005 with Dr. Chengliang Lu and Dr. Kathleen Klueber to develop and commercialize diagnostic tools and therapies for stem cell treatment of multiple degenerative and traumatic neurological diseases. RhinoCyte™ currently has three patents for olfactory stem cell treatments approved in the United States, Australia and Israel, with others pending worldwide.

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Laurel Harper
Laurel92@msn.com
502-550-0089
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Nasal Stem Cells Show Promise in Repairing Spinal Cord Damage Caused by Contusion