Category Archives: Cell Medicine

Mast cells, components of the immune system, are responsible for alleriges and asthma, conditions that debilitate millions. Yet relatively few scientists study them.

Hydar Ali of the University of Pennsylvania is a member of the select group of researchers for whom mast cells are a focus. A professor in the Department of Pathology and director of faculty advancement and diversity in Penns School of Dental Medicine, Ali has spent his career discerning the cells unique qualities and honing in on strategies to modulate their activity to improve health.

Obviously Im biased, but I do think that our findings are critically important, Ali said. These cells are relatively poorly understood, and yet weve been able to identify some of the most sought-after molecular targets to affect diseases like allergies and asthma that have the potential to kill.

Mast cells are part of the immune system and reside in tissues rather than in the blood stream. They are important for protecting the body from pathogens and contribute to wound healing but are most notorious for their involvement in inflammatory and allergic conditions. They are rich in histamine which is released when mast cells are activated and can lead to the quintessential signs of an allergic reaction: hives, itching and even anaphylaxis.

No living human has ever been shown to lack mast cells, and mutant mice that lack them are unable to fight microbial infection, said Ali, so its pretty clear that mast cells are there to protect us from infection. But the other side of the coin is that people who have too many mast cells can develop skin rashes, itch, nausea, vomiting, diarrhea and abdominal pain.

Because mast cells are present only in low numbers and cannot be extracted from the tissue, they are considered difficult to work with, and thus the pool of researchers who do so is limited.

Despite these hurdles, Ali started working with mast cells while pursuing his doctorate at University College London. His dissertation examined the diversity of mast cell types.

I looked at mast cells from different tissues and found tremendous heterogeneity, he said. So, for example, if you took a mast cell from the gut, that cell is different from one in the skin. Theres also variability when you go to different species, so there are major differences between mouse mast cells, rat mast cells and human mast cells.

These differences make translational work, moving from animal models to human treatments, a challenge, as Ali and many of his colleauges in the field have discovered.

After earning his Ph.D., Ali moved into a postdoctoral position at the National Institutes of Health, where a handful of labs focused on mast cells. He recalls headline-making news when scientists in a neighboring lab cloned the gene for the IgE receptor. This receptor binds IgE antibodies and triggers a signaling pathway associated with allergic diseases, eczema and other condtions.

I remember The New York Times said that a therapy for asthma was on the way, Ali said. You read so many things like this and they never come, but this was different.

Indeed, by the 2000s an asthma drug came on the market to target this receptor

Ali saw that the field was ripe for discovery. Wanting to continue his rearch in academica, he took a position at Duke University, working with Ralph Snyderman, who was then chancellor of health affairs. Snydermans research portfolio primarily examined white blood cells other than mast cells, notably neutrophils and macrophages, but Ali helped discover that mast cells could be used as a model system to study properties of neutrophil receptors in a different context.

In 1998, Ali was ready to run his own lab. He had had the good fortune of being awarded grants, from the NIH, American Lung Association and American Heart Association, all to study G protein coupled receptors, which, like IgE receptors, are present in large numbers on mast cells.

At Duke, he had discovered that one of these G-protein coupled receptors, or GPCRs, was activated by a protein called C3a, part of the complement pathway that can often promote inflammation. High levels of C3a was also known to be associated with an increased risk of asthma in humans.

After coming to Penn, Ali serendipitously discovered the presence of a new GPCR, known as MRGPRX2, which is found only on mast cells and not other immune cells.

Pursuing this finding led Ali and colleagues to find that small proteins called antimicrobial peptides, which were believed to only kill microbes directly, could activate mast cells through MRGPRX2 to harness the protective function of mast cells to help clear the invading microbes.

Working with Penn Dentals Henry Daniell, a professor in the Department of Biochemistry,Ali showed that a couple of these antimicrobial peptides, manufactured through Daniells patented biopharmaceutical plant-production platform, were able to activate the mast cells through MRGPRX2, showcasing the positive role of mast cells in defending the body against pathogens.

I think this highlights the fact that mast cells are playing a role in host defense, said Ali.

On the other side of this fine line, mast cells involvement in pathogenic conditions such as asthma, Alis lab has been at the forefront in discoveries with the potential to translate to human therapies.

Earlier researchers had found that a key receptor involved in chronic asthma and anaphylaxis in mice did not function the same way in humans. Thus much energy that was poured into developing inhibitors of that receptor in mice ended up being fruitless in the pursuit of human therapies.

Yet, Ali and colleagues showed that, in humans, similar effects were elicited by signaling through MRGPRX2. While they had also shown that activating this receptor led to improved antimicrobial effects, in the context of allergic response, blocking this receptor could inhibit the harmful inflammatory effects.

Its two sides of the same coin, Ali said.

With a new set of grants, Alis lab is working with the Fox Chase Chemical Diversity Center to screen for small molecules that mimic known antimicrobial peptides in activating mast cells through the MRGPRX2 and operate with a similar dual function, direct killing and activating mast cells to help in fending off the attack. Theyre also looking for potential drugs that block this receptors activity to reduce the effects of allergic and chronic inflammatory conditions.

In addition, theyre using mouse models that use human version of molecular receptors to continue unraveling the mysteries of mast cells. One project is looking at the association between MRGPRX2 actviation and worsening asthma, while another is looking at the connection between chronic heart and lung diseases and genetic variations in mast cell receptors.

The goal is keeping the work relevant to humans.

With animal models, Ali said, if you think a gene is important, you knock it out, you over express it, you generate a ton of data and can publish it in a very high-impact journal. And when you submit a grant, it looks like youre a very productive investigator, you have impressive results in mice. But the question is, does it relate to humans?

In May, Ali will present his recent findings on the mysteries of controlling mast cells through MRGPRX2 in a keynote lecture at the European Mast Cell and Basophil Research Network International Meeting in Prague.

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Penn Dental Medicine Professor Unlocks the Mysteries of Mast Cells - Penn: Office of University Communications

"Any exercise is better than being sedentary," said Dr. Sreekumaran Nair, senior author of the study and a diabetes researcher at the Mayo Clinic in Rochester, Minnesota. However, Nair noted that high-intensity interval training (HIIT), in particular, is "highly efficient" when it comes to reversing many age-related changes.

High intensity interval training involves short bursts of intense aerobic activity within a stretch of more moderate exercise: intermittently sprinting for 30 seconds, for example, in the middle of a moderate-pace jog.

For the National Institutes of Health-funded study, Nair and his colleagues enlisted the help of both men and women from two age groups: The "young" volunteers ranged in age from 18 to 30; "older" volunteers ranged in age between 65 and 80. Next, the researchers divided these participants into three mixed-age groups and assigned each a different supervised exercise training program lasting three months.

The high-intensity interval training training group did three days a week of cycling, with high-intensity bouts sandwiched between low-intensity pedaling, and two days a week of moderately difficult treadmill walking. The strength training group performed repetitions targeting both lower and upper body muscles just two days each week. Finally, the combined training group cycled (less strenuously than the first group) and lifted weights (fewer repetitions than the second group) for a total of five days a week.

There were clear differences, then, in the amount of time different participants spent in the gym.

Before and after each training session, the researchers assessed various aspects of each volunteer's physiology, including body mass index, quantity of lean muscle mass and insulin sensitivity, one indication of diabetes. The researchers also did routine biopsies of each volunteer's thigh muscles and performed a biochemical analysis in order to establish a comprehensive fingerprint of the muscle.

Analyzing the gathered data, Nair and his colleagues found that all forms of exercise improved overall fitness, as measured by cardiorespiration, and increased insulin sensitivity, which translates into a lower likelihood of developing diabetes. Although all exercise helped with musculature, strength training was most effective for building muscle mass and for improving strength, which typically declines with age.

Meanwhile, at the cellular level, high-intensity interval training yielded the biggest benefits.

Specifically, in the HIIT group, younger participants saw a 49% increase in mitochondrial capacity, while older participants saw a 69% increase. Most cells in our bodies contain infrastructure known as mitochondria. These "organelles" -- a mini-version of an organ within a cell -- perform as tiny batteries do, producing much-needed energy.

Interval training also improved volunteers' insulin sensitivity more than other forms of exercise. Drilling down deeper, Nair and his colleagues compared the protein-level data gathered from participants to understand why exercise provided these benefits.

If we think of the cell as a corporate hierarchy, genes (DNA) are the executives issuing orders to their middle managers: messenger RNA. Tasked with transcribing this order, the RNA turns to ribosomes, which perform a supervisory role by linking amino acids in order to assemble protein molecules. Finally, the proteins, cellular work horses, carry out the task originally dictated by the gene.

"Proteins sustain environmental damage and the damaged proteins have to be ... replaced with newly synthesized (produced) proteins," explained Nair in an email. "With aging in sedentary people, production of many protein molecules decline. ... Gradually the quantity of these protein molecules decrease causing functional decline."

Analyzing the muscle biopsies, the researchers discovered that exercise boosts cellular production of mitochondrial proteins and the proteins responsible for muscle growth.

"Exercise training, especially high intensity interval training, enhanced the machinery (ribosomes) to produce proteins, increased the production of proteins and enhanced protein abundance in muscle," Nair said. He said the results also showed that "the substantial increase in mitochondrial function that occurred, especially in the older people, is due to increase in protein abundance of muscle."

In some cases, the high-intensity regimen actually seemed to reverse the age-related decline in both mitochondrial function and muscle-building proteins.

Exercise's ability to transform mitochondria could explain why it benefits our health in so many different ways, according to the authors. Muscle cells, like brain and heart cells, are unusual in that they divide only rarely compared with most cells in the body. Because muscle, brain and heart cells do wear out yet are not easily replaced, the function of all three of these tissues are known to decline with age, noted Nair.

If exercise restores or prevents deterioration of mitochondria and ribosomes in muscle cells, exercise possibly performs the same magic in other tissues, too. And, although it is important simply to understand how exercise impacts the mechanics of cells, these insights may also allow researchers "to develop targeted drugs to achieve some of the benefits that we derive from the exercise in people who cannot exercise," Nair said.

"We cannot have enough studies surrounding this information because of how impactful it is for health," said Trilk, who was not involved in the research. She explained that if younger people boost mitochondrial function when they're young, they would be preventing disease, while for an older population, they would also be preventing disease while maintaining skeletal muscle, which wanes in older age.

"Mitochondrial function is important to almost every cell in the human body," Trilk said. "So when you don't have mitochondrial function or when you have mitochondrial dysfunction, you have dysfunction of cells, so from a molecular standpoint, you start seeing cellular dysfunction years before you start seeing the global effect, which ends up coming out as symptoms of diseases: diabetes, cancers and cardiovascular disease."

"A strength is that they studied males and females," Zierath said, though she noted that the number of participants in each group was "quite small." Still, this is a minor flaw.

"It teases out some of the training regimes that might be leading to greater effects on what they call mitochondrial fitness," she said. Compared with the other two exercise programs, interval training "really had a more robust effect" on the machinery of cells, she said.

"It boosted the proteins that are important for mitochondrial function -- the oxygen powerhouse of the cells," Zierath said. "It reversed many of what we call age-related differences in mitochondrial function and oxidative metabolism."

"Part of what happens with HIIT is, you disturb homeostasis, you exercise at a really high level, and the body needs to cope with that," she explained.

Even though one program had superior effects, "every single exercise protocol they tested had positive effects," said Zierath, who is looking forward to future research in this vein.

"We need to understand even more about how the human body adapts to different exercise regimes and how this can be important for mitigating what we see as sort of aging-related changes that occur in the functionality of muscle and the ability of the muscle to metabolize fuel, sugar and fat," she said.

"Exercise is almost a medicine in some respects," Zierath said. "It's never too late to start exercising."

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Interval training exercise could be a fountain of youth - CNN

Targeting cancer stem cells may be a more effective way to overcome cancer resistance and prevent the spread of squamous cell carcinoma the most common head and neck cancer and the second-most common skin cancer, according to a new study by cancer researchers at the UCLA School of Dentistry.

Head and neck squamous cell carcinoma is a highly invasive form of cancer and frequently spreads to the cervical lymph nodes. Currently, cisplatin is the standard therapeutic drug used for people with HNSCC. Yet, more than 50 percent of people who take cisplatin demonstrate resistance to the drug, and they experience a recurrence of the cancer. The five-year survival rates remain sorely low and researchers still dont understand the underlying mechanisms behind head and neck squamous carcinoma. Therefore, said UCLA cancer biologist Dr. Cun-Yu Wang, who led the study, theres an urgent need to understand why people with this type of cancer are resistant to therapy and to develop new approaches for treating it.

Wangs researchis published online today in the peer-reviewed journal Cell Stem Cell.

Cancer stem cells are known to be responsible for tumor formation and development; they also self-renew and tend to be unresponsive to cancer therapy. These cells have been found in head and neck squamous cell carcinoma. Given the unique challenges that cancer stem cells pose for oncologists, it remains unclear what the optimal therapeutic strategy is for treating HNSCC.

To address this, Wang, who holds the Dr. No-Hee Park Endowed Chair in Dentistry at UCLA and holds a joint appointment in the UCLA Department of Bioengineering, and his research team first developed a mouse model of head and neck squamous cell carcinoma that allowed them to identity the rare cancer stem cells present in HNSCC usingin vivolineage tracing, a method to identify all progeny of a single cell in tissues.

The researchers found that the cancer stem cells expressed the stem cell protein Bmi1 and had increased activator protein-1, known as AP-1, a transcription factor that controls the expression of multiple cancer-associated genes. Based on these new findings, the UCLA team developed and compared different therapeutic strategies for treating head and neck squamous cell carcinoma. They found that a combination of targeting cancer stem cells and killing the tumor mass, consisting of high proliferating cells, with chemotherapy drugs resulted in better outcomes.

The team further discovered that cancer stem cells were not only responsible for squamous cell carcinoma development, but that they also cause cervical lymph node metastasis.

This study shows that for the first time, targeting the proliferating tumor mass and dormant cancer stem cells with combination therapy effectively inhibited tumor growth and prevented metastasis compared to monotherapy in mice, said Wang, who is a member of the UCLA Jonsson Comprehensive Cancer Center and of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. Our discovery could be applied to other solid tumors such as breast and colon cancer, which also frequently metastasizes to lymph nodes or distant organs.

With this new and exciting study, Dr. Wang and his team have provided the building blocks for understanding the cellular and genetic mechanisms behind squamous cell carcinoma, said Dr. Paul Krebsbach, dean of the UCLA School of Dentistry. The work has important translational values. Small molecule inhibitors for cancer stem cells in this study are available or being utilized in clinical trials for other diseases. It will be interesting to conduct a clinical trial to test these inhibitors for head and neck squamous cell carcinoma.

Additional authors of the study include Demeng Cheng, first author and postdoctoral scholar in Wangs lab; Mansi Wu, Yang Li, Dr. Insoon Chang, Yuan Quan, Mari Salvo, Peng Deng, Dr. Bo Yu, Yongxin Yu, Jiaqiang Dong, John M. Szymanski, Sivakumar Ramadoss and Jiong Li who are all from the laboratory of molecular signaling in the division of oral biology and medicine at the UCLA School of Dentistry.

This work was supported in part by the National Institute of Dental and Craniofacial Research grants R37DE13848, R01DE15964 and R01DE043110.

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Targeting cancer stem cells improves treatment effectiveness and ... - UCLA Newsroom

March 9, 2017 Rohit Kulkarni, M.D., Ph.D., Senior Investigator at Joslin Diabetes Center, and Professor of Medicine at Harvard Medical School. Credit: John Soares

If you become resistant to insulin, a condition that is a precursor to type 2 diabetes, your body tries to compensate by producing more of the "beta" cells in the pancreas that produce the critical hormone. Researchers have long sought to understand why these cells often fail to proliferate in people who go on to develop the disease. Studying both humans and mice, scientists at Joslin Diabetes Center now have pinpointed one key biological mechanism that can prevent the cells from dividing successfully.

Better understanding of the beta-cell proliferation process eventually may lead toward therapies for diabetes patients, whose supplies of these cells often shrink over time, says Rohit Kulkarni, M.D., Ph.D., a Joslin Senior Investigator and senior author on a paper about the work published in the journal Cell Metabolism.

Previous studies of beta cell proliferation generally have focused on mechanisms that kick off the cell cycle that leads to successful cell division. "Most adult mammalian beta cells are in a quiescent phase, and so if you want to push them into the cell cycle, you need to shake them out of their sleep," explains Kulkarni, who is also a Professor of Medicine at Harvard Medical School. Over the years, scientists have discovered a number of biological mechanisms that help to initiate the cell cycle.

"However, very often many of the beta cells that begin the cell cycle don't complete it, because the regulatory signals aren't appropriate," Kulkarni notes. "The cells choose to die because that's an easier route than completing the cell cycle."

Seeking to understand this failure to divide, his lab previously analyzed beta cells that were modified to lack an insulin receptor and didn't divide as easily as normal beta cells. Among their findings, the scientists saw that these cells generated significantly smaller amounts than normal beta cells of two proteins that partner to help separate the cell's chromosomes just before the cell divides.

In their latest research, the Joslin team performed many experiments to explore the actions of these two proteins, called centromere protein A (CENP-A) and polo-like kinase-1 (PLK1), in mice and in cells from humans and mice.

Among their experiments, the researchers studied beta cell signaling in mice that were modified to lack expression of the proteins and experienced insulin resistance by being placed on a high-fat diet, or aging, or becoming pregnant. "We showed that mice that lacked the CENP-A protein could not compensate for insulin resistance by making more insulin-secreting cells," Kulkarni says.

Additionally, his team examined human beta cells and found lower levels of CENP-A and PLK-1 proteins in cells from donors with diabetes compared to cells from healthy donors.

To better understand how insulin signaling affects beta-cell growth, the Joslin scientists next studied a pathway involving a protein called FOXM1. This protein acts as a "transcription factor" that regulates genes by binding to their DNA regions. FOXM1 helps to drive cell proliferation, and it can promote the expression of CENP-A and PLK-1.

"We found that insulin signaling can initiate the binding of this transcription factor with PLK-1 and CENP-A, in both mouse and human beta cells," Kulkarni says. "This binding is lost in beta cells lacking the insulin receptor, and the loss of binding leads to cell death rather than division."

"We also discovered that this type of regulation is, interestingly, specific to beta cells, and not seen in other metabolic cell types such as liver and fat cells," he says.

Given this new insight into how beta cells divide or fail to divide, "our next step will be to begin to ask whether we can target FOXM1 or other proteins in the pathway to enable a better progression through the cell cycle and to generate more beta cells," Kulkarni says.

The research may hold the eventual promise of treatments not only for type 2 diabetes but for type 1 diabetes, in which beta cells are wiped out by autoimmune attack, he adds.

Joslin's Jun Shirakawa was first author on the paper. Other contributors, all from Joslin, included Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin Okawa, Wei Zhang, Peng Yi and Alessandro Doria. The National Institutes of Health provided lead funding for the study.

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Researchers at the Universities of Dundee and Edinburgh in Scotland are looking to work with the pharmaceutical industry to improve understanding of the biological processes that could form the basis of new therapies to support tissue regeneration or repair.

The National Phenotypic Screening Centre (NPSC) at the University of Dundee and the Medical Research Council (MRC) Centre for Regenerative Medicine (CRM) at the University of Edinburgh have signed a Memorandum of Understanding to work more closely together on translating novel biological discoveries into new stem cell therapies that could address a wide range of conditions.

The UK Regenerative Medicine Platform-funded Engineering and exploiting the stem cell niche Hub, led by the CRM, is dedicated to increase understanding of the biology of stem cell niches and to exploiting this knowledge therapeutically to improve organ regeneration through endogenous repair and cell transplantation.

Finding new drugs which can activate endogenous regenerative pathways requires the development of cell-based assays able to reproduce the complex behaviour of the cells and tissues in patients; the NPSC specialises in developing such assays so they can be systematically screened using large libraries of drug-like molecules to uncover agents that can alter cell and tissue behaviour.

The alliance between the two centres will allow novel biological discoveries from CRM to benefit from the expertise and industrial drug screening infrastructure provided by the NPSC, which, it is hoped, will lead to new therapies.

Stem cell medicine is coming of age. This is a great opportunity for Scottish Universities to partner with industry to ensure we can translate excellent science to new therapies that can help patients with chronic disease, noted Professor Stuart Forbes, Director of the Centre for Regenerative Medicine and co-director of the Niche Hub.

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Scottish universities link to develop stem cell therapies - PharmaTimes - PharmaTimes

It is common knowledge that exercise imparts a smorgasbord of health benefits. What is not yet understood is how physical activity manages to reduce aging on a cellular level. New research into mitochondria lifts the lid on the processes involved.

Regular exercise has been shown to boost the immune system, heighten cognitive abilities, improve sleep, increase lifespan, and maintain muscle tone. Its benefits are proven; the research is conclusive.

However, the mechanisms that lie beneath exercise's positive effects remain in the shadows. How do physical activities translate into rebuilding organelles that degrade as we age? Which activities are best?

A new study, published this week in Cell Metabolism, takes a look under the hood and provides clues as to how these benefits might be produced.

The current study's senior author is Dr. Sreekumaran Nair, a diabetes researcher at the Mayo Clinic in Rochester, MN, and the research team was led by Matthew Robinson, who now works at the University of Oregon in Eugene.

In all, the study included 36 men and 36 women, split into two age groups: "young" (aged between 18 and 30) and "older" (aged between 65 and 80). These participants were further split into three exercise programs:

Taking a biopsy from the volunteer's thigh muscles, they compared the molecular makeup with a control group of sedentary volunteers. Lean muscle mass and insulin sensitivity were also assessed.

The team found that, although strength training was effective at building muscle mass, high-intensity interval training had the greatest effect at a cellular level, specifically on mitochondria.

Mitochondria are commonly referred to as the powerhouses of the cell; their primary function is to produce adenosine triphosphate - the molecule that transports chemical energy within cells. As we age, the capacity of mitochondria to generate energy slowly decreases.

By comparing proteomic and RNA-sequencing data across the exercise groups, the team found that exercise encourages cells to make more RNA copies of the genes that code for mitochondrial proteins and proteins responsible for muscle growth.

Younger volunteers carrying out interval training showed a 49 percent increase in mitochondrial capacity and, even more impressively, the older group saw a 69 percent increase.

High-intensity biking effectively reversed age-related decline in mitochondrial function.

Ribosomes, vital players in the synthesis of proteins, also received a boost from exercise - it increased their ability to build mitochondrial proteins, which explains the rise in both mitochondrial function and muscle hypertrophy.

Physical activity's ability to bolster protein production is important. Muscle cells, like brain and heart cells, do not divide frequently. This means that, as we age, function declines. As Dr. Nair explains: "Unlike liver, muscle is not readily regrown. The cells can accumulate a lot of damage." If exercise can restore or minimize the deterioration of ribosomes and mitochondria in muscle cells, there is a good chance that it does the same in other tissues.

In addition to the increase in mitochondrial capacity, the interval training also improved the participant's insulin sensitivity, lowering the risk of developing diabetes. However, this exercise type was less effective at improving muscle strength.

"Based on everything we know, there's no substitute for these exercise programs when it comes to delaying the aging process. These things we are seeing cannot be done by any medicine."

Dr. Sreekumaran Nair

Although this study was not focused on making recommendations about duration or exercise type, Dr. Nair says: "If people have to pick one exercise, I would recommend high-intensity interval training, but I think it would be more beneficial if they could do 3-4 days of interval training and then a couple of days of strength training."

The study clearly demonstrates how exercise can increase the output of specific organelles. This relationship is likely to play a key part in slowing cellular aging.

Dr. Nair and his team plan to extend their deep dive into the cellular benefits of exercise in other tissue types. In the future, these findings could potentially be used to target specific pathways and reduce the impact of aging. In time, perhaps these positive changes could be triggered artificially, but as Dr. Nair says: "There are substantial basic science data to support the idea that exercise is critically important to prevent or delay aging. There's no substitute for that."

Learn how just 20 minutes of exercise can reduce inflammation.

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Exercise prevents cellular aging by boosting mitochondria - Medical News Today

Three Medicine-Related Advances Make MIT's List of Breakthrough Technologies Managed Care magazine ... each type of cell a ZIP code in the three-dimensional space of the human body, according to the report. In September 2016, Facebook CEO Mark Zuckerberg and his wife made the cell atlas the inaugural target of a $3 billion donation to medical ... and more »

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Three Medicine-Related Advances Make MIT's List of Breakthrough Technologies - Managed Care magazine

In the United States, about 90,000 people, mostly blacks, suffer from the sickle cell disease, and worldwide, an estimated 275,000 babies are born with it each year. Photo credit: the Guardian

A new groundbreaking medical procedure by a team of researchers at Necker Childrens Hospitalin France promises hope for sickle cell disease patients.

Using pioneering treatment, scientists at Necker Childrens Hospital in Paris have succeeded in reversing the disease in a French teenager, reports BBC.

According to the doctors, they were successfully able to alter the genetic instructions in the bone marrow of the teenager to get it to produce healthy red blood cells.

Doctors removed his bone marrow, which manufactures blood. They then genetically altered it in a lab to compensate for the defect in his DNA that caused the disease.

The teenager now 15 underwent the procedure at the hospital in 2014, and scientists say the results so far have been very encouraging with about half of his red blood cells having normal haemoglobin.

Results published by the researchers in the New England Journal of Medicine show the teenager has been making normal blood in the months following the procedure.

Professor Philippe Leboulch, one of the lead scientists on the groundbreaking medical procedure, said that while it is too early to call the procedure a cure for sickle cell disease, it does provide a necessary respite for the teenager.

So far the patient has no sign of the disease, no pain, no hospitalization. He no longer requires a transfusion so we are quite pleased with that.

But of course we need to perform the same therapy in many patients to feel confident that it is robust enough to propose it as a mainstream therapy.

Before the treatment, the teen had to visit the hospital every month to have a transfusion to dilute his defective blood. He also suffered significant internal damage that caused his spleen to be removed and his hips to be replaced.

Dr. Deborah Gill, gene researcher at the University of Oxford, believes the results are a huge step forward and opens new frontiers in treatment for sickle cell sufferers.

Ive worked in gene therapy for a long time and we make small steps and know theres years more work.

But here you have someone who has received gene therapy and has complete clinical remission thats a huge step forward, Dr. Gill said.

Another reported setback is the fact that the expensive procedure can only be carried out in cutting-edge hospitals and laboratories far away from the countries in sub-Saharan Africa where the majority of sickle cell sufferers live with Keith Wailooadding in the New England Journal of Medicine that vexing questions of race and stigma have shadowed the history of the medical treatment of the disease.

Sickle cell disease mainly affects people with African, Caribbean, or Middle Eastern ancestry. In the United States, mostly African Americans are affected, and worldwide, about 275,000 babies are born with it each year.

Illustration showing the difference between normal and sickled red blood cell formations. Photo credit: General Health

In sickle cell sufferers, normally round red blood cells, which carry oxygen around the body, are defective and shaped like a sickle. Those cells can sometimes lock together, clogging tiny blood vessels and causing bouts of extreme pain, organ damage, and even death.

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New Medical Procedure Promises Hope for Sickle Cell Patients - Face2Face Africa

Bacteria and antibiotics have been in an arms race since the drugs were invented. But for economic reasons, fewer and fewer of these drugs are being developed today, while the fear of antibiotic-resistant bacteria is ever-growing. This, and the potential threat of a bioterror attack, where say an epidemic-causing bacteria is released into the general population, makes the need for countermeasures obvious. Johns Hopkins researchers have come up with a new way to eliminate dangerous bacteria, using beefed up cells who seek out and destroy dangerous pathogens, all on their own.

Researchers from the John Hopkins Whiting School of Engineering and the School of Medicine teamed up on this four-year project. They received a grant of $5.7 million, awarded by the federal agency DARPA (Defense Advanced Research Projects Agency). The point of the study is to create a biocontrol system that can send out single-cell enforcers to find and eliminate certain pathogens. Researchers will program amoeba cells to do so, each one micron long, about one-tenth the width of a human hair.

These amoeba are independent and travel on their own surfaces--meaning they can get potentially deadly pathogens wherever they may be. In the event they are needed, they would be emitted through a spray. As a first step, scientists hope to program the cells to go after the bacteria which causes Legionnaires disease.

It could also be used to target Pseudomonas aeruginosa, a dangerous, potentially deadly, treatment-resistant strain of pneumonia. In another scenario, specially engineered amoeba cells are unleashed by health officials if an outbreak occurs. There are other uses too. They could sterilize instruments, and studying them may even reap benefits for cancer research.

So whats DARPAs interest? These biochemical warriors may someday help dampen down or even counteract a bioterror attack. They could also be used to render contaminated soil harmless. The innovation here is that each cellular soldier is self-directed. It does not depend on an outside human operator. Principal investigator Pablo A. Iglesias likened it to a self-driving car. Iglesias is a professor of electrical and computer engineering at Johns Hopkins.

Amoebas.By C.G. Ehrenberg (Die Infusionthierchen, 1830) [Public domain], via Wikimedia Commons

Just as cruise control slows down or speeds up a car, Iglesias said, In a similar way, the biocontrol systems were developing must be able to sense where the pathogens are, move their cells toward the bacterial targets, and then engulf them to prevent infections among people who might otherwise be exposed to the harmful microbes.

Iglesias started looking into biocontrol systems 15 years ago. To develop this particular type of synthetic biology, he is teaming up with four colleagues at the school of medicine. Each is a biological chemistry expert. Douglas N. Robinson, a professor of cell biology is on the team. He likened what these amoebas do to bacteria to what humans do when they encounter freshly baked cookies. They seek to gorge themselves unabashedly.

Though the technique has a lot of potential, Iglesias admitted to the Baltimore Sun, that past experiments in the field havent actually gone very well. "People manage to do things but it takes huge amounts of effort and it's more or less random, he said. There has to be a lot of iterations before it works." Other experts say, this teams efforts are heartening, particularly due to the growing menace of antibiotic-resistant bacteria.

Researchers are using amoeba cells called Dictyostelium discoideum in their experiments. This species is commonly studied. It can be found in the damp soil of riverbeds. These microbes surround bacteria and devour them. Turns out the bacteria let off a biochemical scent that the amoeba, using a specific type of receptor, pick up.

Robinson said that their experiments must adhere to the strictest operating protocols, lest such amoeba escape into the environment and wreak havoc. If this project bears fruit, researchers believe theyll have a new tool to fight infection in hospitals, and protect society against bioterror and ecological disasters. So far, scientists are targeting only pathogens lurking outside the human body. In this contract, we are not targeting bacteria in human blood, Iglesias said. But the hope is that the techniques we develop would ultimately be useful for that.

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Researchers Engineer Enforcer Cells That Will Take out Lethal Bacteria - Big Think

Time to Supply Private Stem Cell Clinics?

Boston, MA (PRWEB) March 07, 2017

Recent scientific reports put the number of private clinics offering stem cell medical treatments in the U.S. at greater than 400. More than 300 of these clinics emerged since 2009. They mirror the rapid increase in FDA-approved clinical trials during the same period at a rate of about 300 new therapy-focused adult tissue stem cell trials each year. However, because of the inherently small number of patients enrolled in early clinical trials and the much larger number of patients seen in medical clinics, the number of stem cell treatments performed in private clinics dwarfs the number in clinical trials by more than 10-fold.

In both settings, treatment cell transplants per se appear generally safe, as long as proper care is given to other routine safety factors, which include mainly keeping treatments free of infectious agents and chemical contaminants and avoiding immune reactions. These safety procedures fall well within the training and expertise of physicians in private clinics, as well as in hospital-based clinical trials.

The rapid growth of private stem cell clinics has alarmed some stem cell scientists and their member organizations. The clinics are accused of making false claims, exploiting patients pain and distress for financial gain, and generally harming the reputation of stem cell science. In contrast, in FDA-approved clinical trials, patient volunteers are necessarily informed that their treatments are experimental, and therefore may bring them no medical benefit. Generally, trial subjects do not pay for their treatment, though often treatment costs are covered by their personal health insurance.

Asymmetrexs founder and director, James L. Sherley, M.D., Ph.D., recently began a public discourse, in which he argues that in the important respects private stem cell clinics are not all that different than FDA-approved clinical trials. First, he says that glibly painting all several hundred or more private stem cell clinics as exploitive is an unsubstantiated claim itself. Generally, physicians in both settings are diligently looking for ways to improve the health of patients clinical trial physicians in the more distant future and private clinic physicians immediately. Sherley, a physician scientist, stresses the importance of recognizing medical empiricism as an important contributor to the advance of modern medicine and medical science.

At the conference, Sherley is scheduled to lead a panel discussion on the topic on March 8 at 15:50 PM (EDT) and give a talk on March 9 at 13:30 PM (EDT). A major new position he will present is that the volume of stem cell treatments now occurring in private clinics is much too large to simply disparage and attempt to shut down. Working to improve the quality of private stem cell clinic treatments for patients and to improve their documentation towards accelerating progress in stem cell medicine is a better goal.

To attendees at this weeks Clinical Trials Supply conference, Sherley will suggest that the supply of private stem cell clinics with high quality, certified sources of stem cells is an underappreciated crucial need for advancing stem cell medicine. The companies that are able to mobilize to fill in this supply gap could have a 10-fold greater impact on advancing stem cell medicine compared to their current minimal impact in FDA-approved stem cell clinical trials.

About Asymmetrex

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrexs founder and director, James L. Sherley, M.D., Ph.D. is an internationally recognized expert on the unique properties of adult tissue stem cells. The companys patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Currently, Asymmetrexs focus is employing its technological advantages to develop and market facile methods for monitoring adult stem cell number and function in stem cell transplantation treatments and in pre-clinical assays for drug safety.

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Asymmetrex's Head Will Lead Discussion on Supplying Private Stem Cell Clinics at the 6th Annual Clinical Trial ... - PR Web (press release)