Stem Cell Clinic

Mouse model of human immune system inadequate for stem cell … – Medical Xpress

By Stem Cell Medicine

August 22, 2017 Credit: Martha Sexton/public domain

A type of mouse widely used to assess how the human immune system responds to transplanted stem cells does not reflect what is likely to occur in patients, according to a study by researchers at the Stanford University School of Medicine. The researchers urge further optimization of this animal model before making decisions about whether and when to begin wide-scale stem cell transplants in humans.

Known as "humanized" mice, the animals have been engineered to have a human, rather than a murine, immune system. Researchers have relied upon the animals for decades to study, among other things, the immune response to the transplantation of pancreatic islet cells for diabetes and skin grafts for burn victims.

However, the Stanford researchers found that, unlike what would occur in a human patient, the humanized mice are unable to robustly reject the transplantation of genetically mismatched human stem cells. As a result, they can't be used to study the immunosuppressive drugs that patients will likely require after transplant. The researchers conclude that the humanized mouse model is not suitable for studying the human immune response to transplanted stem cells or cells derived from them.

"In an ideal situation, these humanized mice would reject foreign stem cells just as a human patient would," said Joseph Wu, MD, PhD, director of Stanford's Cardiovascular Institute and professor of cardiovascular medicine and of radiology. "We could then test a variety of immunosuppressive drugs to learn which might work best in patients, or to screen for new drugs that could inhibit this rejection. We can't do that with these animals."

Wu shares senior authorship of the research, which will be published Aug. 22 in Cell Reports, with Dale Greiner, PhD, professor in the Program in Molecular Medicine at the University of Massachusetts Medical School, and Leonard Shultz, PhD, professor at the Jackson Laboratory. Former postdoctoral scholars Nigel Kooreman, MD, and Patricia de Almeida, PhD, and graduate student Jonathan Stack, DVM, share lead authorship of the study.

"Although these mice are fully functional in their immune response to HIV infection or after transplantation of other tissues, they are unable to completely reject the stem cells," said Kooreman. "Understanding why this is, and whether we can overcome this deficiency, is a critical step in advancing stem cell therapies in humans."

"Humanized mice are critical preclinical models in many biomedical fields helping to bring basic science into the clinic, but as this work shows, it is critical to frame the question properly," said Greiner. "Multiple laboratories remain committed to advancing our understanding and enhancing the function of engrafted human immune systems."

Greiner and Shultz helped to pioneer the use of humanized mice in the 1990s to model human diseases and they provided the mice used in the study.

Understanding stem cell transplants

The researchers were studying pluripotent stem cells, which can become any tissue in the body. They tested the animals' immune response to human embryonic stem cells, which are naturally pluripotent, and to induced pluripotent stem cells. Although iPS cells can be made from a patient's own tissues, future clinical applications will likely rely on pre-screened, FDA-approved banks of stem cell-derived products developed for specific clinical situations, such as heart muscle cells to repair tissue damaged by a heart attack, or endothelial cells to stimulate new blood vessel growth. Unlike patient-specific iPS cells, these cells would be reliable and immediately available for clinical use. But because they won't genetically match each patient, it's likely that they would be rejected without giving the recipients immunosuppressive drugs.

Humanized mice were first developed in the 1980s. Researchers genetically engineered the mice to be unable to develop their own immune system. They then used human immune and bone marrow precursor cells to reconstitute the animals' immune system. Over the years subsequent studies have shown that the human immune cells survive better when fragments of the human thymus and liver are also implanted into the animals.

Kooreman and his colleagues found that two varieties of humanized mice were unable to completely reject unrelated human embryonic stem cells or iPS cells, despite the fact that some human immune cells homed to and were active in the transplanted stem cell grafts. In some cases, the cells not only thrived, but grew rapidly to form cancers called teratomas. In contrast, mice with unaltered immune systems quickly dispatched both forms of human pluripotent stem cells.

The researchers obtained similar results when they transplanted endothelial cells derived from the pluripotent stem cells.

A new mouse model

To understand more about what was happening, Kooreman and his colleagues created a new mouse model similar to the humanized mice. Instead of reconstituting the animals' nonexistent immune systems with human cells, however, they used immune and bone marrow cells from a different strain of mice. They then performed the same set of experiments again.

Unlike the humanized mice, these new mice robustly rejected human pluripotent stem cells as well as mouse stem cells from a genetically mismatched strain of mice. In other words, their newly acquired immune systems appeared to be in much better working order.

Although more research needs to be done to identify the cause of the discrepancy between the two types of animals, the researchers speculate it may have something to do with the complexity of the immune system and the need to further optimize the humanized mouse model to perhaps include other types of cells or signaling molecules. In the meantime, they are warning other researchers of potential pitfalls in using this model to screen for immunosuppressive drugs that could be effective after human stem cell transplants.

"Many in the fields of pluripotent stem cell research and regenerative medicine are pushing the use of the humanized mice to study the human immune response," said Kooreman. "But if we start to make claims using this model, assuming that these cells won't be rejected by patients, it could be worrisome. Our work clearly shows that, although there is some human immune cell activity, these animals don't fully reconstitute the human immune system."

The researchers are hopeful that recent advances may overcome some of the current model's limitations.

"The immune system is highly complex and there still remains much we need to learn," said Shultz. "Each roadblock we identify will only serve as a landmark as we navigate the future. Already, we've seen recent improvements in humanized mouse models that foster enhancement of human immune function."

Explore further: Study provides hope for some human stem cell therapies

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Stem Cell Treatments for Lung Diseases Advance – Healthline – Healthline

By Stem Cell Medicine

Two new studies look at using stem cells from lungs to combat fibrosis and other lung-related diseases.

Stem cell treatments for lung diseases may have taken a big step forward according to a pair of studies published earlier this month.

In one animal study, researchers did transbronchial biopsies, sending miniscule tweezers down the throats of rats in order to obtain lung cells.

The researchers were able to culture tens of millions of cells and inject them into rats that had a condition similar to idiopathic pulmonary fibrosis.

Rats that received the injected cells showed less lung inflammation and overall healthier lung cells than those that didnt receive the cells.

Both studies, published in the journals Respiratory Research and Stem Cells Translational Medicine, built upon research into stem cell therapies for heart diseases, and less successful work on lung diseases like emphysema.

Both offer new hope for fibrosis patients, whose current treatment options are medications to reduce symptoms, or a lung transplant.

The new research raises the possibility of reversing the impacts of fibrosis and similar diseases that cause lung inflammation, which gradually damages lung tissue and makes internal organs less able to transfer oxygen to the blood.

Its also the first time stem cells have been gathered and reproduced using the minimally invasive biopsy method, researchers said.

Lung stem cells are most often obtained surgically.

That requires putting the patient on a ventilator and cutting out a small piece of lung, said Dr. Jason Lobo, an assistant professor at the University of North Carolina School of Medicine, and co-author of the new papers.

Using the method employed by the researchers, Lobo told Healthline, medical professionals can tweeze out a few cells and send patients home the same day.

However, minimally invasive may be a relative term.

Its not as invasive as opening up your chest, but if youve ever had a tube stuck down your throat, you wouldnt call it noninvasive, Dr. Norman Edelman, senior scientific advisor to the American Lung Association, told Healthline.

But Edelman calls the new research exceedingly interesting.

Stem cells are hot, he said. People are doing a lot of interesting things with stem cells, and I expect eventually theyll hit on something, and maybe this it.

Edelman cautions, however, that theres been a long history of stem therapy for lung diseases, most of it not very satisfactory.

He points specifically to work using stem cells to fight emphysema. He said the therapies havent been proven to be successful, but have led to a number of clinics outside the United States providing Americans with stem cell treatments not yet approved by the U.S. Food and Drug Administration (FDA).

The American Lung Association has cautioned against these unregulated stem cell therapies.

Lots of interesting things in rats and mice dont turn out, said Edelman, who wasnt involved in the latest studies.

But he expects the University of North Carolina researchers would go through all the necessary safeguards when they start testing in humans and not offer it as something more than experimental.

Lobo said they hope to have FDA approval to begin human trials by the end of the year. Those would start within six months after the approval.

We might have to do more mouse trials, but the last time we met with the FDA, we got the feeling they werent leaning that way, Lobo said.

They would join about a dozen other clinical trials looking into the use of various types of stem cells to combat pulmonary fibrosis.

Stem cells are young enough that they can still grow up to become any number of specialized cells, potentially including mature lung tissue cells.

Other research into stem cell therapies has largely focused on mesenchymal stromal cells, which have immunosuppressive qualities but arent necessarily obtained from lungs.

Lobo and his co-authors focused on resident lung cells, which they figured would more easily graft to the lungs and survive a hypothesis backed up in a 2015 paper.

While their current research is focused on idiopathic pulmonary fibrosis, they hope the therapies, if successful, may eventually help people with related diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis. and fibro-cavernous pulmonary tuberculosis.

Asked whether a cure for lung cancer could be on the horizon, Lobo said probably not, due to the different nature of the disease.

But hopefully we will be able to extend into other diseases... any chronic lung disease, he said.

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Stem Cell Treatments for Lung Diseases Advance - Healthline - Healthline

UTMB lung experiment flies into space – Austin American-Statesman

By Stem Cell Medicine

GALVESTON

Two hundred and fifty miles above the Earths surface, scientists have begun testing the limits of human biology. In the sterile environment of the International Space Station, cells are being prodded to grow and multiply.

The goal is to grow human body parts, without the rest of the human attached.

The experiment sounds like a plot for a science fiction movie. But its actually one of the newest experiments to be conducted on the space station. The experiment, launched this month, was designed by a University of Texas Medical Branch team.

Researchers aim to study how stem cells develop in a zero-gravity environment. The results could lead to new possibilities to help with long-distance space flight and terrestrial medical treatments, said Joan Nichols, a professor of internal medicine, and microbiology and immunology and the associate director of the Galveston National Laboratory.

The experiment was developed over the past five years. It was launched as part of the payload aboard a SpaceX Dragon Cargo ship. The ship carried 6,400 pounds of equipment, experiments and supplies, including a freezer with Blue Bell ice cream cups.

Nichols and her team spent the week before the launch in Florida, preparing the experiment. It went off without a hitch, and the capsule arrived at the space station.

Everything went smoothly, Nichols said.

Nichols has studied lungs and their development on a cellular level for 15 years. The lab, which is focused on studying how lungs grow and heal, is no stranger to pushing scientific boundaries. In 2015, researchers from the lab successfully transplanted a bioengineered lung into a living pig.

Over time, the limits of growing cells on Earth has become apparent, she said. Studies have already shown that stems cells grow and multiply better in a zero-gravity environment than they do down below, she said.

The results could be used to develop treatments for problems astronauts develop on a long space flight, such as lung disease or traumatic injury.

Weve discovered what our limits are for doing large tissue constructs is the fact that the stem cells dont proliferate very well, Nichols said. Stem cells stay stemmy in space, she said, they dont mature and become other types of cells as fast.

If the cells stay stemmier and produce better, thats a huge thing that we cant do here on Earth, Nichols said. It will answer some questions about these cells.

Nichols and her team will be in communication with NASA and the astronauts on the space station over the six-week course of the experiment. While tests are done in space, her team will replicate the experiment at the Galveston National Laboratory, to provide a control sample to compare the results.

Being able to expand the UTMB program to the stars has been a dream come true, Nichols said.

Being at Kennedy and Cape Canaveral, and working at the lab there, at the building where all the Apollo missions happened I grew up with that, Nichols said. We worked hard and there were really long days, but it really was the most amazing experience ever.

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UTMB lung experiment flies into space - Austin American-Statesman

These Six Startups From Y Combinator’s Demo Day 1 Are Ready to Transform Our World – Futurism

By Stem Cell Medicine

A Room Full of Ideas

Great ideas,given the proper support, can change the world. Thats one of the reasons seed funding provider Y Combinator helps innovative startups acquire the financial resources they need to put their ideas into action. Since 2005, theyvefunded about 1,500 startups, and two times every year, they present some of those companies to investors via a three-day event known as Demo Day.

For the firstdayof Y Combinators Summer 2017Demo Day event, the startup accelerator presented 50 companies that all have remarkable potential. While you can check them all out on TechCrunch,the following six startups earn our vote as the most futuristic of them all.

Founded by a group of medical doctors and biomedical research scientists, Forever Labs combines two of the most advanced fields in modern medicine: stem cells and anti-aging research.

The startups current staff of 20 doctors wants to take a different approach to fighting age-related diseases by cryogenically freezing stem cells that can be used to combat such diseases when a person is older.

According to the company, stem cell storage couldgrow into a $56 billion market, and the figure doesnt seem outlandish considering the rapid pace at which anti-aging studies and stem cell research have been advancing lately.

Sunuisanother startup with a health-focus, only instead of combatting aging, their goal is to help those who suffer from visual impairments.

The company wants to help blind people navigate streets without having to depend on a cane or a guide dog. To do this, the startup has developed a sonar bracelet or smartwatch that vibrates to alert visually impaired people of nearby objects.

Sunu band combines sonar or echolocation with gentle precise vibrations to inform the user about objects or obstacles within their environment, according to the companys website. After beta-testing the device for six months, Sunu says it managed to reduce the chances that their vision-impaired users got into accidents by 90 percent.

Not all of the startups featured at Demo Day were focused on health and medicine, though this next one combines materials engineering withtextile science.

Kestrel Materialshas designed a fabric thats a step-up from breathable and waterproof types, and their goal is simple enough: reduce the need for bulky layers. To do this, the startup has created an adaptive material that reacts to cold and warmth.

When exposed to cold surroundings, the fabric flexes and creates air pockets that trap heat and keep people warm. During warmer weather, the air pockets collapse and prevent heat from being trapped in the clothing. Since the material uses common fibers, such as nylon and polyester, the applications for such an adaptive fabric are as plentiful as the styles of clothes people wear.

Few things scream future quite likeflying cars, and the next two startups are looking to extend their reach into that space.

First is Skyways, a startup based in Austin, Texas, thats building vertical take-off and landing (VTOL) delivery drones. While they arent exactly the kinds of flying cars you may expect to one day operate yourself, delivery drones like Skyways are positioned to be just as big a part of that flying future.

Skyways drones are capable of hauling loads of up to roughly 20 kilograms (45 pounds), and the company wants to use them to provide the military with a transportation service that doesnt put peoples lives at risk.

Now, this startup takes flying cars to the next level.

Pykawants to make autonomous single-person aircraft a part of our reality, and theyve already built a 181 kilogram (400 pound) one that can fly itself.

While theyre ironing out the tons of regulations requiredfor commercial use of this transportation system, Pykas taken on a side gig in New Zealand as an autonomous crop duster.

Speaking of autonomous tech and farming, thisstartup wants to employ robots as vegetable farmers.

Modular Science, as their name suggests, is into building modular machines for agriculture, and one of their products is a specialized plant-farming robot. The companys goal is to automate 99 percent of the vegetable farming process in the next six months.

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These Six Startups From Y Combinator's Demo Day 1 Are Ready to Transform Our World - Futurism

Can Sirolimus Help Patients with Fibrodysplasia Ossificans Progressiva? – Rare Disease Report

By Induced Pluripotent Stem Cells

Fibrodysplasia ossificans progressiva (FOP) is a devastating disease that has no treatment and very few options on the horizon, but that could change soon. As early as September, a clinical trial testing rapamycin (also known as sirolimus) in FOPpatients could begin.

FOP is a very rare genetic condition, striking about 1 in every 2 million people. The disease involves the growth of a second skeletal in the body as the child ages. As the skeletal growth continues, most patients will die as a result of the chest being unable to move and the person stops breathing.

Sirolimus is an immunosuppressive drug currently approved for treating patients with another rare disease, lymphangioleiomyomatosis(LAM) that largely affects the lungs.

Rapamycin was chosen from studies involving induced pluripotent stem cells(iPS) being grown to mimic FOP cells, and using those cells to test a number of drugs to see if they are effective. The researchers at the Kyoto Universitys Center for iPS Cell Research and Application (CiRA) tested 6,800 substances and found 1 drug that drug inhibited abnormal bone formation rapamycin.

The clinical trial may also trigger a greater appreciation for the value that iPS cells can provide in the drug discovery process.

Shinya Yamanaka, director of the CiRA and co-recipient of the 2012 Nobel Prize in Physiology or Medicine for the creation of iPS cells said, I hope the clinical trial will become the start of wider drug development using iPS cells, and lead to cures for many rare diseases.

For more clinical trial news, follow Rare Disease Report at FacebookandTwitter.

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Can Sirolimus Help Patients with Fibrodysplasia Ossificans Progressiva? - Rare Disease Report

Reprogramming ‘Fixes’ Trisomic Sperm – Asian Scientist Magazine

By Induced Pluripotent Stem Cells

AsianScientist (Aug. 22, 2017) - Scientists have found a way to remove extra sex chromosomes that cause genetic infertility to produce healthy offspring. These findings, published in Science, offer a potential new approach to tackling a common genetic cause of human infertility.

Our sex is determined by the X and Y chromosomes. Usually, girls have two X chromosomes (XX) and boys have one X and one Y (XY), but approximately 1 in 500 boys are born with an extra X or Y, a condition known as trisomy. Men with Klinefelter syndrome have an extra X chromosome (XXY) while men with double Y syndrome are XYY.

In the present study, researchers from Kyoto University, the Japan Science and Technology Agency, the Japan Society for the Promotion of Science and the Francis Crick Institute have found that reprogramming cells from trisomic mice can cause the loss of the extra chromosome. Sperm generated from the resulting corrected induced pluripotent stem (iPS) cells could be used to create healthy, fertile offspring.

Firstly, the team took small pieces of ear tissue from XXY and XYY mice, cultured them and collected connective tissue cells known as fibroblasts. They turned the fibroblasts into stem cells and noticed that in the process, some of the cells lost the extra sex chromosome.

With an existing method, they used specific chemical signals to guide the stem cells into becoming cells that have the potential to become sperm. These cells developed into mature sperm when injected into the testes of a host mouse. The researchers then harvested these mature sperm and used them through assisted reproduction to create healthy, fertile offspring.

Our approach allowed us to create offspring from sterile XXY and XYY mice, said first author Dr. Takayuki Hirota from the Francis Crick Institute. It would be interesting to see whether the same approach could one day be used as a fertility treatment for men with three sex chromosomes.

In a preliminary experiment, the team found that stem cells produced from fibroblasts of men with Klinefelter syndrome also lost the extra sex chromosome. However, lots more research is needed before this approach could ever be used in humans, the researchers said.

There is currently no way to make mature sperm outside of the body, explained study senior author Dr. James Turner, Group Leader at the Francis Crick Institute.

In our mouse experiments we have to inject cells that have the potential to become sperm back into the testes to help them finish developing. But we found that this caused tumours in some of the mouse recipients. So reducing the risk of tumour formation or discovering a way to produce mature sperm in a test tube will have to be developed before we can even consider this in humans.

The article can be found at: Hirota et al. (2017) Fertile Offspring from Sterile Sex Chromosome Trisomic Mice.

Source: Francis Crick Institute; Photo: Shutterstock. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Reprogramming 'Fixes' Trisomic Sperm - Asian Scientist Magazine

Link between cells associated with aging and bone loss – Medical Xpress

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August 21, 2017 Osteoblasts actively synthesizing osteoid. Credit: Robert M. Hunt; Wikipedia.

Mayo Clinic researchers have reported a causal link between senescent cells - the cells associated with aging and age-related disease - and bone loss in mice. Targeting these cells led to an increase in bone mass and strength. The findings appear online in Nature Medicine.

Low bone mass and osteoporosis are estimated to be a major public health threat for almost 44 million U.S. women and men 50 and older, according to the National Osteoporosis Foundation. Bone is a living tissue that is constantly being broken down and replaced. Osteoporosis occurs when the creation of new bone doesn't keep up with the removal of old bone.

"While we know from previous work that the accumulation of senescent cells causes tissue dysfunction, the role of cell senescence in osteoporosis up to this point has been unclear," says Sundeep Khosla, M.D., director of the Aging Bone and Muscle program at Mayo Clinic's Robert and Arlene Kogod Center on Aging. "The novelty of this work for the bone field lies in the fact that, rather than targeting a bone-specific pathway, as is the case for all current treatments for osteoporosis, we targeted a fundamental aging process that has the potential to improve not only bone mass, but also alleviate other age-related conditions as a group."

In the study, researchers used multiple approaches to target senescent cells in mice with established bone loss between 20 and 22 months of age. That's the equivalent of over age 70 in humans. Approaches included using:

"The effects of all three approaches on aging bone were strikingly similar," says Dr. Khosla. "They all enhanced bone mass and strength by reducing bone resorption but maintaining or increasing bone formation, which is fundamentally different from all current osteoporosis drugs."

The benefits on bone found in elderly mice were not evident in younger mice. That, coupled with the finding that the senolytic drugs were effective when given only intermittently, supports the link between senescent cells and age-related bone loss. Researchers administered a senolytic drug combination (dasatinib and quercetin) once per month to eliminate senescent cells.

"Even though this senolytic drug combination was only present in the mice for a couple of hours, it eliminated senescent cells and had a long-lasting effect," says James Kirkland, M.D., Ph.D., director of the Kogod Center on Aging and co-corresponding author of the study. "This is another piece of the mounting evidence that senolytic drugs are targeting basic aging processes and could have widespread application in treating multiple chronic diseases."

Drs. Kirkland and Khosla say that being able to administer the drugs intermittently poses less risk for side effects than with drugs that must be taken daily. Also, current therapeutics in the bone field that treat bone loss "work against themselves," meaning that, if they decrease resorption, they also decrease formation. In this study, the senolytic drugs decreased bone resorption, while maintaining or increasing bone formation.

"With the aging of the population in the U.S. and around the world, age-related bone loss is going to continue to be an enormous public health problem, and patients with osteoporosis have a higher risk for other age-related comorbidities," says Dr. Khosla. "By combining the knowledge of three separate labs and enlisting the expertise of several others in a true team science approach, we were able to collaborate and make these findings possible. We need to continue to pursue these potential interventions that target fundamental aging mechanisms as, hopefully, an eventual way to reduce the burden of fractures and other conditions, such as cardiovascular dysfunction, diabetes and frailty."

Explore further: Researchers uncover new agents

More information: Targeting cellular senescence prevents age-related bone loss in mice, Nature Medicine (2017). DOI: 10.1038/nm.4385

Journal reference: Nature Medicine

Provided by: Mayo Clinic

Mayo Clinic researchers have uncovered three new agents to add to the emerging repertoire of drugs that aim to delay the onset of aging by targeting senescent cells - cells that contribute to frailty and other age-related ...

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Study sheds light on why some breast cancers have limited response to immunotherapy – Medical Xpress

By Uncategorized

August 21, 2017 Jonathan Serody, M.D., UNC Lineberger member and the Elizabeth Thomas Professor in the UNC School of Medicine, is first author of a study that investigated why drugs that are designed to unleash the immune system against cancer were ineffective in a type of triple negative breast cancer with a heavy presence of immune cells. Credit: Brian Strickland/UNC Lineberger

UNC Lineberger Comprehensive Cancer Center researchers have identified a possible reason why some aggressive breast cancers are unresponsive to certain immunotherapy treatments, as well as a potential solution.

In the Journal of Clinical Investigation, researchers report on their study that explored a perplexing question: Why were drugs designed to unleash the immune system against cancer ineffective in a type of triple negative breast cancer with a heavy presence of immune cells? Their findings could lead to a strategy to improve immunotherapy responses in the "claudin-low" subtype of breast cancer.

"We were trying to figure out why a tumor made up, in some instances, of half immune cells doesn't respond to a treatment that should ramp up immune cells present in the tumor," said the study's senior author Jonathan Serody, MD, UNC Lineberger member and the Elizabeth Thomas Professor in the UNC School of Medicine. "I think it's important for us to try to start segregating out the types of tumors that don't respond to these treatments at a much granular genomic level, and try to figure out new mechanisms to enhance the response rate to immunotherapy."

The American Cancer Society estimates that approximately 12 percent of breast cancers are "triple negative," meaning they lack three cell surface receptors that are known to help drive the cancer. Triple negative breast cancer tumors typically grow faster and come back sooner than other breast cancer types. There are no targeted treatments for these cancers.

In a subset of triple negative breast cancers known as "claudin low," researchers found an elevated level of immune cells in and around the tumors. They believed this would help the body fight the cancer. However, the researchers found the opposite: "Checkpoint inhibitors," a type of immunotherapy that works by unlocking the immune system's brakes against cancer, were ineffective in this subtype.

They determined with gene expression analysis that, instead of being flooded with immune cells that attack cancer tumors, claudin-low tumors had a high concentration of regulatory T-cells - a type of immune cell that suppresses the body's defenses. Claudin-low tumors were releasing a chemical signal to attract these regulatory T-cells.

"This regulatory T-cell population is preventing the immune system from rejecting the cancer," said UNC Lineberger's Benjamin Vincent, MD, an assistant professor in the UNC School of Medicine. "We thought if we could get rid of those cells, we could help the immune system better fight the breast cancer cells."

In an effort to allow the immune-stimulating cancer treatments to work, the researchers tested an investigational approach to deplete the regulatory T-cells, and they combined the treatment with a checkpoint inhibitor in order to try to improve outcomes. This combination slowed tumor growth. They believe they have identified a key aspect of what is preventing immunotherapy treatments from working.

"This finding may shed some light on why response rates to immunotherapy treatments remain low in triple negative breast cancer," Vincent said. "We are looking to understand why patients who don't respond don't respond, and what we can do to render their tumors immunotherapy responsive."

Vincent is helping to lead a clinical trial testing this strategy to improve responses to checkpoint inhibitors. Researchers also believe these findings may also underscore the need to study other cancer types at a genomic level to understand differences in response rates to immunotherapy treatments.

"This speaks to the mission of UNC Lineberger, which is to conduct groundbreaking basic science research, but always with the mission of extending and improving the lives of patients as our end goal," Vincent said.

Explore further: A molecular subtype of bladder cancer resembles breast cancer

More information: Nicholas A. Taylor et al, Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI90499

Journal reference: Journal of Clinical Investigation

Provided by: UNC Lineberger Comprehensive Cancer Center

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Police: Fugitive’s death ‘breaks’ cell behind Spain attacks – Medicine Hat News

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By Joseph Wilson, Aritz Parra And Lori Hinnant, The Associated Press on August 21, 2017.

SUBIRATS, Spain The lone fugitive from the Spanish cell that killed 15 people in and near Barcelona was shot to death Monday after he flashed what turned out to be a fake suicide belt at two troopers who confronted him in a vineyard not far from the city he terrorized, authorities said.

Police said they had scientific evidence that Younes Abouyaaqoub, 22, drove the van that barrelled through Barcelonas crowded Las Ramblas promenade, killing 13 people on Thursday, then hijacked a car and fatally stabbed its driver while making his getaway.

Abouyaaqoubs brother and friends made up the rest of the 12-man extremist cell, along with an imam who was one of two people killed in what police said was a botched bomb-making operation.

After four days on the run, Abouyaaqoub was spotted outside a train station west of Barcelona on Monday afternoon. A second witness told police she was certain she had seen the man whose photo has gone around the world as part of an international manhunt.

Two officers found him hiding in a nearby vineyard and asked for his identification, according to the head of the Catalan police. He was shot to death when he opened his shirt to reveal what looked to be explosives and cried out Allah is great in Arabic, regional police chief Josep Luis Trapero said.

A bomb disposal robot was dispatched to examine the downed suspect before police determined the bomb belt was not real, Trapero said. A bag full of knives was found with his body, police said.

A police photo of the body seen by The Associated Press showed his bloodied face, bearing several days stubble on the chin.

With Abouyaaqoubs death, the group responsible for last weeks fatal van attacks has now been broken, Trapero said.

The arrest of this person was the priority for the police because it closed the detention and dismantling of the group that we had identified, he said.

Four are under arrest, and eight are dead: five shot by police in the seaside town of Cambrils, where a second van attack left one pedestrian dead early Friday; two others killed on the eve of the Barcelona attack in a botched bomb-making operation; and Abouyaaqoub.

The Islamic State group has claimed responsibility for both the Cambrils and Barcelona attacks.

Roser Ventura, whose father owns a vineyard between the towns of Sadurni dAnoia and Subirats, said she alerted the regional Catalan police when they spotted a car crossing their property at high speed.

The police told us to leave the premises and go home. We heard a helicopter flying around and many police cars coming toward the gas station that is some 600 metres from the property, Ventura said.

The search for Abouyaaqoub ended on the same day that Catalan police confirmed that he was the last remaining cell member thought to still be at large and provided a timeline of his movements.

Authorities said earlier Monday they had evidence that pinpointed Abouyaaqoub as the driver of the van that plowed down the Las Ramblas promenade, killing 13 pedestrians and injuring more than 120 others.

Trapero said that after abandoning the vehicle, Abouyaaqoub walked through Barcelona for about 90 minutes, through the famed La Boqueria market and nearly to Barcelona University.

The Spanish newspaper El Pais published images Monday of what it said was Abouyaaqoub leaving the van attack site on foot. The three images show a slim man wearing sunglasses walking through La Boqueria.

In a parking lot often used by university students, he then hijacked a Ford Focus belonging to Pau Perez, stabbing Perez to death and taking the wheel with his final victims body in the backseat. Minutes later, Abouyaaqoub plowed through a police checkpoint with the stolen car and abandoned the vehicle, disappearing into the night.

The manhunt for him reached well beyond Spains borders, but in the end, Abouyaaqoub died about 30 kilometres (18 miles) from where he was last spotted.

After the carnage in Barcelona, authorities took a closer look at an explosion the night before in a house south of the city. Police initially had dismissed it as a household accident.

Along with two bodies, the more exhaustive search turned up remnants of over 100 butane gas tanks and materials needed for the TATP explosive, which has been used previously by Islamic State militants for attacks in Paris and Brussels, among others.

The equipment, along with reports that Abouyaaqoub had rented three vans, suggested the militant cell was making plans for an even more massive attack on the city.

Family and friends of the young men, nearly all with roots in Morocco, described them as well-integrated members of the community in Ripoll, a quintessentially Catalan town nestled into the foothills of the Pyrenees.

I knew everyone implicated in the attacks. These were people who avoided problems, kept their distance when they saw a fight, Saber Oukabir, a cousin of two of the attackers, said.

The group members started spending time with the imam who police think was their ideological leader about six months ago, Oukabir said. I dont know what could have happened, if he manipulated them, if he drugged them or what.

Fernando Reinares, director of the program on global terrorism at Spains Elcano Royal Institute, said imams such as Abdelbaki Es Satty have made strong inroads into the regions community of North African immigrants, often reaching their Spanish-born children.

He successfully exploited the dense, overlapping, pre-existing kinship, friendship and neighbourhood ties between these young Muslims, Reinares said in an email to The Associated Press. One of the reasons why Catalonia is the main scenario for both jihadist radicalization and involvement in the whole of Spain is certainly related to the extraordinary, unparalleled concentration in the region of Salafist congregations and imams, such as Es Satty.

Regional authorities said Monday that 48 people were still hospitalized from the attacks in Barcelona and Cambrils, eight of them in critical condition.

Catalonias regional president, meanwhile, said regional and local authorities had rejected the Spanish governments suggestion to place traffic barriers to protect the Las Ramblas promenade because they deemed them inefficient.

Carles Puigdemont told La Sexta television the barriers wouldnt have prevented vehicles from entering the promenade at other points and he said closing off Las Ramblas was impractical because emergency vehicles still needed access.

On Monday, crowds of people continued to lay flowers, candles and heart-shaped balloons at the top of the pedestrian promenade where the van struck and at other smaller tributes.

Las Ramblas also regained some normality, with throngs of people walking up and down, tourists arriving and residents going about their daily business.

We have to stand strong in front of these betrayers, assassins, terrorists, said resident Monserrat Mora. Because Barcelona is strong and they will not be able to prevail with us.

_____

Parra contributed from Madrid along with Ciaran Giles. Hinnant contributed from Barcelona. Reda Zeireg in Rabat, Morocco contributed.

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Police: Fugitive's death 'breaks' cell behind Spain attacks - Medicine Hat News

Howard University Hosts ‘Be The Match’ Marrow Registry Drive – Howard Newsroom (press release)

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Howard University Hospital's Dr. Ermias Aytenfisu seeks to clear up misconceptions about marrow donation in the minority community.

WASHINGTON, D.C. (August 21, 2017) Elsa Nega is an Ethiopian-Canadian mother of two young children. She loves her children and wants to watch them grow. However, Nega has a rare form of blood cancer, leukemia, and needs a bone marrow transplant to survive.

Black patients like Nega are the least likely to find their suitable blood marrow match, according to Be The Match which is hosting a Stem Cell/Bone Marrow registry event at the Howard University College of Medicine on Wednesday, Aug. 30 between 11 a.m. and 3 p.m. The exact location for the registry drive is the lobby outside of room 1008 in the Numa P. Adams building.

Negas story began in February when she walked into her local ER and was rushed to intensive care. By the next morning Nega was diagnosed with Acute Lymphoblastic Leukemia (ALL) and started on chemo immediately. Unlike 90 percent of patients who go into remission after the first round of chemo, she did not.

Now, after three rounds of chemo, a bone marrow transplant is her only hope of recovery. Negas siblings were not a match and she is reaching out to the Washington region because of its large population of people of Ethiopian descent.

There are a lot of myths associated with marrow donation, said Amanda Holk, community engagement representative with the Be The Match in Washington, D.C. There is so much fear surrounding the process but most donors are back to work the next day.

ErmiasM. Aytenfisu, M.D., stroke medical director at Howard University Hospital said the most common way to donate bone marrow is through a procedure called peripheral stem cell donation. No surgery is involved. Donors receive medication to increase peripheral stem cells before the donation. On the day of donation, blood is removed through a needle on one arm and passed through a machine that separates out the blood-forming cells. Uncommonly marrow donation involves surgical techniques that use a special needle to take out blood forming cells. During the procedure, the patient is anesthetized and feels no pain.

Joining the bone marrow registry at the Howard University College of Medicine event involves a simple as a cheek swab and an application. A persons chance of being a match at that point is only 1 in 500. But, for a patient like Elsa, you could be the only one. Elsa does not have a single match on the registry although there are 30 million people signed up.

For more information, contact Amanda Holk via email AHolk@nmdp.org or 202-875-9987

For the Howard University registry drive, please note that you must be between the ages of 18 and 44 to join the registry since research has shown that the younger the cells, the better the patient outcomes. And the following conditions prevent you from joining:

Hepatitis B or C

HIV

Organ, marrow or stem cell transplant recipient

Stroke or TIA (transient ischemic attack)

Other upcoming local events to support Elsa Nega:

*Empower the community (The Helen Show)

Date: 08/26/2017 (Sat.)

Location: Washington Convention Center

*Ethiopian Day Festival

Date: 09/03/2017 (Sun.)

Location: Downtown Silver Spring

About Howard University Hospital

Over the course of its roughly 155-year history of providing the finest primary, secondary and tertiary health care services, Howard University Hospital (HUH) remains one of the most comprehensive health care facilities in the Washington, D.C. metropolitan area and designated a DC Level 1 Trauma Center. The hospital is the nation's only teaching hospital located on the campus of a historically Black university. For more information, visit huhealthcare.com

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Howard University Hosts 'Be The Match' Marrow Registry Drive - Howard Newsroom (press release)

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