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BreakThrough Digest Medical News

BreakThrough Digest Medical News


Research supports promise of cell therapy for bowel disease

Posted: 27 Feb 2013 09:00 PM PST

Researchers at Wake Forest Baptist Medical Center and colleagues have identified a special population of adult stem cells in bone marrow that have the natural ability to migrate to the intestine and produce intestinal cells, suggesting their potential to restore healthy tissue in patients with inflammatory bowel disease (IBD).

Up to 1 million Americans have IBD, which is characterized by frequent diarrhea and abdominal pain. IBD actually refers to two conditions ? ulcerative colitis and Crohn’s disease ? in which the intestines become red and swollen and develop ulcers, probably as the result of the body having an immune response to its own tissue.

While there is currently no cure for IBD, there are drug therapies aimed at reducing inflammation and preventing the immune response. Because these therapies aren’t always effective, scientists hope to use stem cells to develop an injectable cell therapy to treat IBD.

The research findings are reported online in the FASEB Journal (the journal of the Federation of American Societies for Experimental Biology) by senior researcher Graca Almeida-Porada, M.D., Ph.D., professor of regenerative medicine at Wake Forest Baptist’s Institute for Regenerative Medicine, and colleagues.

The new research complements a 2012 report by Almeida-Porada’s team that identified stem cells in cord blood that are involved in blood vessel formation and also have the ability to migrate to the intestine.

“We’ve identified two populations of human cells that migrate to the intestine ? one involved in blood vessel formation and the other that can replenish intestinal cells and modulates inflammation,” said Almeida-Porada. “Our hope is that a mixture of these cells could be used as an injectable therapy to treat IBD.”

The cells would theoretically induce tissue recovery by contributing to a pool of cells within the intestine. The lining of the intestine has one of the highest cellular turnover rates in the body, with all cell types being renewed weekly from this pool of cells, located in an area of the intestine known as the crypt.

In the current study, the team used cell markers to identify a population of stem cells in human bone marrow with the highest potential to migrate to the intestine and thrive. The cells express high levels of a receptor (ephrin type B) that is involved in tissue repair and wound closure.

The cells also known to modulate inflammation were injected into fetal sheep at 55 to 62 days gestation. At 75 days post-gestation, the researchers found that most of the transplanted cells were positioned in the crypt area, replenishing the stem cells in the intestine.

“Previous studies in animals have shown that the transplantation of bone-marrow-derived cells can contribute to the regeneration of the gastrointestinal tract in IBD,” said Almeida-Porada. “However, only small numbers of cells were successfully transplanted using this method. Our goal with the current study was to identify populations of cells that naturally migrate to the intestine and have the intrinsic ability to restore tissue health.”

Almeida-Porada said that while the two studies show that the cells can migrate to and survive in a healthy intestine, the next step will be to determine whether they can survive in an inflamed intestine.

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The research was supported by the National Heart, Lung, and Blood Institute under award number NHL097623 and HL073737 and grant P20 RR-016464 from the Idea Network of Biological Research Excellence Program of the National Center for Research Resources.

Co-authors were Saloomeh Mokhtari, Christopher D. Porada, and Melisa Soland, Wake Forest Baptist; and Evan Colletti, Craig Osborne, Karen Schlauch, Deena El Shabrawy, Takashi Yamagami, and Esmail D. Zanjani, University of Nevada. The two projects were performed while Almeida-Porada was at the University of Nevada prior to joining Wake Forest Baptist.

Media Contacts: Karen Richardson, krchrdsn@wakehealth.edu, (336) 716-4453 or Main Number (336) 716-4587.

About the Wake Forest Institute for Regenerative Medicine

The Wake Forest Institute for Regenerative Medicine is dedicated to the discovery, development and clinical translation of regenerative medicine technologies. The institute has used biomaterials alone, cell therapies, and engineered tissues and organs for the treatment of patients with injury or disease. Institute scientists were the first in the world to engineer a replacement organ in the laboratory that was successfully implanted in patients. The Institute is based at Wake Forest Baptist Medical Center, a fully integrated academic medical center located in Winston-Salem, North Carolina. The institution comprises the medical education and research components of Wake Forest School of Medicine, the integrated clinical structure and consumer brand Wake Forest Baptist Health, which includes North Carolina Baptist Hospital and Brenner Children’s Hospital, the commercialization of research discoveries through the Piedmont Triad Research Park, as well a network of affiliated community based hospitals, physician practices, outpatient services and other medical facilities.

Contact: Karen Richardson
krchrdsn@wakehealth.edu
336-716-4453
Wake Forest Baptist Medical Center

UCLA study could explain why some people get zits and others don’t

Posted: 27 Feb 2013 09:00 PM PST

The bacteria that cause acne live on everyone’s skin, yet one in five people is lucky enough to develop only an occasional pimple over a lifetime. What’s their secret?

In a boon for teenagers everywhere, a UCLA study conducted with researchers at Washington University in St. Louis and the Los Angeles Biomedical Research Institute has discovered that acne bacteria contain “bad” strains associated with pimples and “good” strains that may protect the skin.

The findings, published in the Feb. 28 edition of the Journal of Investigative Dermatology, could lead to a myriad of new therapies to prevent and treat the disfiguring skin disorder.

“We learned that not all acne bacteria trigger pimples ? one strain may help keep skin healthy,” said principal investigator Huiying Li, an assistant professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA. “We hope to apply our findings to develop new strategies that stop blemishes before they start, and enable dermatologists to customize treatment to each patient’s unique cocktail of skin bacteria.”

The scientists looked at a tiny microbe with a big name: Propionibacterium acnes, bacteria that thrive in the oily depths of our pores. When the bacteria aggravate the immune system, they cause the swollen, red bumps associated with acne.

Using over-the-counter pore-cleansing strips, LA BioMed and UCLA researchers lifted P. acnes bacteria from the noses of 49 pimply and 52 clear-skinned volunteers. After extracting the microbial DNA from the strips, Li’s laboratory tracked a genetic marker to identify the bacterial strains in each volunteer’s pores and recorded whether the person suffered from acne.

Next, Li’s lab cultured the bacteria from the strips to isolate more than 1,000 strains. Washington University scientists sequenced the genomes of 66 of the P. acnes strains, enabling UCLA co-first author Shuta Tomida to zero in on genes unique to each strain.

“We were interested to learn that the bacterial strains looked very different when taken from diseased skin, compared to healthy skin,” said co-author Dr. Noah Craft, a dermatologist and director of the Center for Immunotherapeutics Research at LA BioMed at Harbor?UCLA Medical Center. “Two unique strains of P. acnes appeared in one out of five volunteers with acne but rarely occurred in clear-skinned people.”

The biggest discovery was still to come.

“We were extremely excited to uncover a third strain of P. acnes that’s common in healthy skin yet rarely found when acne is present,” said Li, who is also a member of UCLA’s Crump Institute for Molecular Imaging. “We suspect that this strain contains a natural defense mechanism that enables it to recognize attackers and destroy them before they infect the bacterial cell.”

Offering new hope to acne sufferers, the researchers believe that increasing the body’s friendly strain of P. acnes through the use of a simple cream or lotion may help calm spotty complexions.

“This P. acnes strain may protect the skin, much like yogurt’s live bacteria help defend the gut from harmful bugs,” Li said. “Our next step will be to investigate whether a probiotic cream can block bad bacteria from invading the skin and prevent pimples before they start.”

Additional studies will focus on exploring new drugs that kill bad strains of P. acnes while preserving the good ones; the use of viruses to kill acne-related bacteria; and a simple skin test to predict whether a person will develop aggressive acne in the future.

“Our research underscores the importance of strain-level analysis of the world of human microbes to define the role of bacteria in health and disease,” said George Weinstock, associate director of the Genome Institute and professor of genetics at Washington University in St. Louis. “This type of analysis has a much higher resolution than prior studies that relied on bacterial cultures or only made distinctions between bacterial species.”

Acne affects 80 percent of Americans at some point in their lives, yet scientists know little about what causes the disorder and have made limited progress in developing new strategies for treating it. Dermatologists’ arsenal of anti-acne tools ? benzoyl peroxide, antibiotics and Accutane (isotretinoin) ? hasn’t expanded in decades. Most severe cases of acne don’t respond to antibiotics, and Accutane can produce serious side effects.

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The research was supported by a grant (UH2AR057503) from the National Institutes of Health’s Human Microbiome Project through the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Co-authors include co-first author Sorel Fitz-Gibbon, Bor-Han Chiu, Lin Nguyen, Christine Du, Dr. Minghsun Liu, David Elashoff, Dr. Jenny Kim, Anya Loncaric, Dr. Robert Modlin and Jeff F. Miller of UCLA; Erica Sodergren of Washington University; and Dr. Marie Erfe of LA BioMed.

Washington University: Caroline Arbanas, arbanasc@wustl.edu 

314-286-0109

LA BioMed: Laura Mecoy, lmecoy@labiomed.org
310-546-5860

Contact: Elaine Schmidt
eschmidt@mednet.ucla.edu
310-794-2272
University of California – Los Angeles Health Sciences

Human trials for Streptococcus A vaccine

Posted: 27 Feb 2013 09:00 PM PST

Griffith University’s Institute for Glycomics has launched human trials for a vaccine against Streptococcus A, the germ that causes rheumatic fever.

Severe damage to a patient’s heart is just one of the possible long term consequences of rheumatic fever. Former Prime Minister Kevin Rudd has twice had heart surgery to repair damage suffered from rheumatic fever when he was a child.

Professor Michael Good, Principal Research Leader at the Institute for Glycomics has devoted more than 20 years to beating this disease. The key to the vaccine lies in targeting a particular protein found on the surface of Strep A bacteria.

“Previous studies have shown that the vaccine induces a very effective immune response in rabbits and mice,” Professor Good said.

“The next important step is to ensure that it is safe and does not cause any adverse effects in people, in particular that the vaccine itself doesn’t cause any heart damage.”

Professor James McCarthy, Head of the Infectious Diseases program at the Queensland Institute of Medical Research will carry out the year-long trial involving 20 healthy adults.

“Participants will be monitored very closely for the next 12 months,” Professor McCarthy said.

“Each volunteer will be given two doses of the vaccine and we’ll be watching carefully for any signs of heart problems.”

Rheumatic fever is a major issue in remote Aboriginal and Torres Strait Islander communities in northern Australia.

“Infection rates in these remote Queensland communities are among the highest in the world. Nine out of every ten sufferers in this State are Aboriginal or Torres Strait Islander people,” Professor Good said.

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The vaccine trial is funded by the Co-operative Research Centre for Aboriginal and Torres Strait Islander Health.

Much of Professor Good’s early work was backed by the National Heart Foundation, The Prince Charles Hospital Research Foundation, the United States National Institutes of Health, the Co-operative Research Centre for Vaccine Technology, the Perpetual Foundation and the NHMRC

Contact: Helen Wright
helen.wright@griffith.edu.au
07-373-54288
Griffith University