Lung fibrosis? Stem cell therapy holds promise – The Hindu

A team of scientists from the UNC School of Medicine and North Carolina State University (NCSU), U.S. have developed promising research towards possible stem cell treatment for several lung conditions, such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis, all of which are known to be fatal conditions. In the journal Respiratory Research, the scientists demonstrated that they could harvest lung stem cells from people using a relatively non-invasive, doctors office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy.

In a second study, published in the journal Stem Cells Translational Medicine, the team showed that in rodents they could use the same type of lung cell to successfully treat a model of IPF a chronic, irreversible, and ultimately fatal disease characterised by a progressive decline in lung function. These diseases of the lung involve the build-up of fibrous, scar-like tissue, typically due to chronic lung inflammation. As this fibrous tissue replaces working lung tissue, the lungs become less able to transfer oxygen to the blood. Patients ultimately are at risk of early death from respiratory failure. In the case of IPF, which has been linked to smoking, most patients live for fewer than five years after diagnosis.

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Lung fibrosis? Stem cell therapy holds promise - The Hindu

From one cell to billions: Juan Carlos Izpisa Belmonte studies all stages of life – The San Diego Union-Tribune

Salk Institute researcher Juan Carlos Izpisa Belmonte appears to be everywhere in the field of stem cells and regenerative medicine.

He has helped to invent a new kind of stem cell, performed groundbreaking research in growing human organs in animals and demonstrated in mice how to reverse signs of aging.

In addition, his research has produced mini-kidney organoids from stem cells, pointed to a novel way of preventing mitochondrial disease and most recently, helped to prove that a genetic defect can be efficiently repaired in human embryos. The production of mini-kidneys was chosen by Science magazine in 2013 as a runner-up for its Breakthrough of the Year honor.

Izpisa Belmonte tackles the most difficult problems from conception to old age, including aging itself. Its an interest carried from his youth in Spain, when he became fascinated by the regenerative powers of some animals, powers he would like to confer on humanity.

I am a basic developmental biologist at heart, he said by email from Spain, where he performs research in addition to his Salk lab in La Jolla.

My passion is to study and understand the development of an organism the process by which, after conception, a single cell divides and generates billions of cells and a human being is created. This includes the study of degeneration and regeneration of our cells and organs.

Evan Snyder, a prominent stem cell researcher at the Sanford Burnham Prebys Medical Discovery Institute who has known Izpisa Belmonte since 2003, said: He knows what will be the important questions to answer. The very fact that he can answer them so quickly after theyve been posed means hes been thinking about them already.

Izpisa Belmonte maintains a huge variety of projects in collaboration with colleagues in Europe, the United States and Asia. Snyder and other peers said he succeeds by harnessing imagination with good organizational skills and persistence.

And somehow, while succeeding in the highly competitive field of science, Izpisa Belmonte maintains a courtly, Old World grace and charm, and even humility.

I would say Juan Carlos is one of the most gentle, self-effacing, collaborative, genuinely nice people Ive ever met, Snyder said.

In one instance, Snyder recalled witnessing Izpisa Belmonte encounter a scientist he had beaten to the punch with a discovery. He apologized for having done that and simply said the work just went quicker than expected, Snyder said. It was one of the sweetest things Ive ever seen.

Jun Wu, a Salk researcher in Izpisa Belmontes lab, co-authored the recent study on repairing genetic defects in human embryos. Wu said his first meeting with Izpisa Belmonte was memorable because of that tact and consideration, along with helpful advice.

Hes a good listener, Wu said. He listened to what I had to say about my project. And then he gave me some suggestions. He gave me a lot of freedom to think in my own way, but at the same time he gave me the proper guidance to where I should go.

In other words, Izpisa Belmonte maintains an open-mindedness as a person and scientist, Wu said. Many scientists specialize in particular areas, using a fixed pattern of investigation. Izpisa Belmonte encourages his researchers to explore different paths, and if that path turns out to be wrong, to think about it and learn from that experience.

As scientists, we need to be critical of ourselves, while at the same time we need to be open to the possibility that other people criticizing or saying negative things about us could be right, Wu said.

Izpisa Belmonte was born in 1960 in the small town of Helln in southwestern Spain.

I come from a modest, poor family, he said. My grandfather was a baker, my father left home when I was little and my mother worked in whatever she could to feed me and my brothers.

I left school very early to help earn money for my family by picking almonds, grapes, etc., during harvest time and working as a bellboy before I was even 14, the legal age at that time in my country to start working.

His chief role model was his mother, who taught me the spirit of hard work and fairness, he said.

I remember I used to read a lot, first comics and later on more serious things, mostly classical philosophy. I always remember having a special interest and curiosity to know more about the meaning of life.

But while reading philosophy, Izpisa Belmonte also entertained more worldly fantasies, particularly about being a soccer player.

I even managed to play on a professional soccer team, he said. However, just when I thought that I had a bright future as a player, the coach sat me on the substitutes bench for several months and I realized that perhaps I was not good enough. I then decided that my footballing dream was over and I decided to go back to school. I think the soccer coach that didnt let me play was very decisive for my scientific career.

For that career, Izpisa Belmonte traveled to the big city, Valencia, to enroll in college. Uncertain of his academic path, he chanced on pharmacology.

I am very satisfied with my decision, he said. What I learned there, especially in the subjects of biology and chemistry, was key for me to dedicate my life afterward to try to understand how life, a living organism, is generated.

He earned a series of degrees, including a Ph.D. from the University of Valencia and the University of Bologna in Italy. He did postdoctoral work in Germany and at UCLA.

As a young scientist, he focused on his first big question: How is an embryo formed from one cell, and how does it develop into a complete organism? From that question came early discoveries, including key genes and mechanisms for the formation of organs and limbs, and how they are arranged in the body.

Izpisa Belmonte arrived at the Salk Institute for Biological Studies in 1993, and is now a professor in the Gene Expression Lab. In 2011, he was named as the first holder of the Roger Guillemin Chair, endowed with $3 million by San Diego philanthropists Irwin and Joan Jacobs.

Guillemin, also a Salk professor, received the 1977 Nobel Prize for physiology or medicine.

Guillemin recalls that when he met Izpisa Belmonte, he was struck by the mans purposeful demeanor.

Immediately I knew that this was a very serious young man, that he knew what he was talking about, Guillemin said. From what I understand of the science, hes at the very frontier of whats possible in molecular biology.

In the most recent research, Izpisa Belmonte was one of five senior authors of a study that demonstrated in human embryos that a genetic defect can be corrected. The defect causes a heart disease called hypertrophic cardiomyopathy. It can cause sudden death in apparently healthy people, such as young athletes.

While the embryos werent allowed to develop for more than several days, the study provided proof of principle that such defects can be fixed right around the time of conception.

This is the type of problem that modern molecular biology can look into and become proficient at affecting, Guillemin said.

Last year, Izpisa Belmonte received a grant of at least $2.5 million over five years to study how to generate functional primate organs in pigs, using stem cell technologies he and colleagues developed.

The grant was a Pioneer Award from the National Institutes of Health, given to individual scientists of exceptional creativity who propose pioneering and highly innovative approaches with the potential to produce an unusually high impact on biomedical or behavioral research.

Getting organs of one species to grow in another is difficult, but Izpisa Belmonte said if tissues are implanted at the right time and under the right conditions, a host animals body could provide the proper signaling needed to direct organ development.

Early this year, a team including Izpisa Belmonte reported success in creating a rat-mouse mixture that grew functional organs. They did this by disabling a single gene in single-cell mouse embryos that was needed for development of a specific organ. They then added rat stem cells, which took the place of the vacant mouse organ. This method yielded functional rat eye, heart and pancreas tissue in the mouse.

They tried a somewhat similar experiment in pigs, which proved more difficult. Pigs gestate for about three months and three weeks, while human pregnancies extend for nine months. By experimenting with different kinds of human stem cells, the team finally produced human-pig embryos that grew for about three weeks before they were killed.

While both human and pig cells were present in the embryos, the rate of human cell survival was low. The research team is trying to overcome this challenge by selectively disabling genes in the pig embryos, as they did in the mouse embryos.

Along with the technical challenges, ethical considerations must be met.

For example, allowing human brain tissue to develop in a pig might produce an animal with a partially human consciousness. Thats not likely in the pig-human experiments, because there was no sign that the human cells ever got into the pig brains to begin with.

Izpisa Belmonte downplays his role in the various groundbreaking projects, preferring to give most of the credit to those in his lab.

My role is perhaps the least important of all in our team, he said. I am very fortunate to have many talented junior and senior research scientists working with me. They all have different backgrounds and expertise, not just scientifically, but also culturally, since many of them come from abroad. This has enabled us to think about a problem from different angles and see things more comprehensively.

Equally important, he said, is the scientific and administrative support at the Salk Institute, a true scientific paradise.

I have visited many other institutions and I feel that there is no place that can compare. Most of our best ideas and projects come through interactions with my faculty colleagues and learning from the incredible discoveries and conceptual advances they produce.

Most of his friends come from the world of science, Izpisa Belmonte said, expressing some regret that he let science interfere with some of his relationships.

I had a very close friend who died very young, and I didnt have many other friends in my youth, he said. Friendships are like plants; they need to be fertilized from time to time to grow well, and unfortunately, I did not dedicate time to this.

It was also difficult because I moved from country to country very often during my scientific pursuits. Now I have some colleagues that, after working with them, have become good friends.

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From one cell to billions: Juan Carlos Izpisa Belmonte studies all stages of life - The San Diego Union-Tribune

Got allergies? Scientists may have finally pinpointed the cells that trigger reactions – Science Magazine

Researchers have identified the cells that unleash allergy symptoms such as sneezing.

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By Mitch LeslieAug. 2, 2017 , 2:00 PM

If you sneeze your way through ragweed season or need a restraining order against your neighbors cat, researchers finally know what part of your immune system you should blame. A new study nails down the specific group of cells that orchestrates allergic reactions, a result that could help scientists determine not only why some people have allergies, but also how to block them.

Its exciting for those of us who are looking at potential ways to treat allergic diseases, says Thomas Casale, an allergist and immunologist at the University of South Florida in Tampa who wasnt connected to the study.

Allergies stem from mistaken identity, when some of our immune cells respond to benign substancesknown as allergensthat include pollen, mold spores, and certain foods. Researchers know that the culprits that touch off allergic symptoms belong to a group of T cells known as TH2 cells. But not all TH2 cells are culpable. Some guard us against parasites and other invaders. Sorting the beneficial TH2 cells from the rogues has proveddifficult, however.

In the new study, researchers led by T cell biologist Erik Wambre and immunologist William Kwok of the Benaroya Research Institute at Virginia Mason in Seattle, Washington, obtained blood samples from patients who were sensitive to pollen from alder trees, a common cause of winter and spring allergies. An allergic patients TH2 cells recognize and respond to an allergen because they carry receptors, proteins that match allergen molecules. To tag immune cells carrying receptors for alder pollen, the team added customized fluorescent proteins known as MHCII tetramers to the patients blood samples.

Along with receptors, TH2 cells are dotted with marker proteins. Like sports fans wearing their favorite teams jersey, immune cells proclaim their identity with these marker proteins. The researchers analyzed the tagged cells to determine their combination of markers. Compared with other TH2 cells, one group sported more copies of two marker proteins and fewer copies of four others. Although none of the proteins was exclusive to the cells, together they provided a signature for this clique of TH2 cells, which the researchers dubbed TH2A cells. T cells can sometimes shift identifies, but the researchers found that TH2A cells remained distinct, even after several cellular generations. When these cells are born, they are born to be pathogenic, Wambre says.

As they report online today in Science Translational Medicine, Wambre, Kwok, and colleagues found that the cells were abundant in the blood of patients with allergies to a variety of triggers, including grass pollen and house dust mites. But they were absent from the blood of people who werent sensitive. The team also tested patients undergoing an experimental treatment called oral immunotherapy to alleviate their peanut allergies. Over about 20 weeks, the participants receive larger and larger doses of allergy-inducing peanut proteins, and this repeated exposure eventually allows them to tolerate peanuts.

We saw a dramatic decrease in TH2A cells after the success of the treatment, Wambre says. The number of these cells in the patients that reacted to peanuts fell by about 90%. Kwok says that the evidence he and his colleagues have accumulated suggests that people with allergies make this specific subset of T cells that probably lead to allergic symptoms.

The work could ultimately benefit patients through new treatments and better ways to monitor the disease, says immunologist Andrew Luster of Massachusetts General Hospital in Charlestown. For example, he notes, scientists could assess trials of oral immunotherapywhich attempts to quell patients allergies with edible doses of food allergensby tracking which treatments were eliminating TH2A cells. Another option, Kwok adds, is that if researchers can determine what molecular signals steer certain T cells to become TH2A cells, they may be able to develop ways to prevent formation of the cells. If researchers succeed in that, they might also prevent a lot of sniffling and scratching.

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Got allergies? Scientists may have finally pinpointed the cells that trigger reactions - Science Magazine

Studying Astronaut Health Could Benefit Medicine for All – TrendinTech

Ever since the Apollo missions, the health of astronauts have suffered long after their time in space was over. From reduced bone density to weakened muscles to cardiovascular damage, low gravity environments take a toll on the human body. Many of the astronauts ailments closely resemble conditions suffered by those of advanced age, from back pain to osteoporosis, the research of low gravity healthcare goes beyond astronauts alone.

Fortunately, the University of California at San Francisco (UCSF) researchers are working to understand, develop protocols and treatments that can help astronauts and the general population.

Even with exercise routines developed to maintain muscle mass and bone density, many astronauts complain of back pain lasting for years after their low gravity exposure. Dr. Jeffrey Lotz of UCSF has been studying the vertebrae of astronauts to understand the source of the problem and was surprised by his results.

Although he thought the cause of pain would be water retention in disks, what would normally be pressed out of them by bone compression due to gravity, instead he found a deterioration in the muscles that support the back bone called the multifidus muscles.

Now, he is working in coordination with NASA to design a series of exercises that target these muscles while also considering the limitations of room on a spaceship and low gravity.

The exercises are not for muscle health alone but include improving bone health. However, as Dr. Daniel Bickle discovered in mouse studies exercise alone is not enough to maintain bone density in space.

According to his studies, the low gravity environment disturbs the signal process between osteoclasts and osteoblasts. In normal bone processes, bone is reinforced when damaged or put under the repetitive stress of walking around in Earths gravity. With those stressors gone in low-gravity, osteocyte cells in bone tissue detect decreased stress in certain areas, then sends an activation signal to reabsorb the extra bone tissue thats no longer need to the osteoclasts. Once the work of the osteoclasts is done, another signal is sent to osteoblasts, which then rebuilds necessary bone.

Because the signal interruption is occurring in the later stage of the process, between the osteoclasts and osteoblasts, bone continues being absorbed but does not get rebuilt while in space.

Astronauts with only six months spent on ISS have a reduced bone density loss of six to nine percent, a loss equal to that typically seen annually in postmenopausal women. Although the astronauts may regain the bone density after a year spent in normal gravity, the bone material is redistributed in such a way that their skeletal structures resemble that of an older adult.

Dr. Bickle thinks that further study into why this happens would not only aid astronauts and deep space travel but could also unlock treatments for osteoporosis.

Another factor leading to reduced bone density in astronauts is radiation exposure, but Dr. Bernard Halloran has discovered an interesting solution for this cause of bone loss.

Although it is unclear why Dr. Hallorans experiments with mice have proven that plum powder reduces the loss of bone due to radiation exposure. While further study is needed to concentrate the mysterious active ingredient into pill form, it is a promising discovery for low-gravity healthcare.

Perhaps the most detrimental of all the effects of spaceflight, and aging is the effect on the cardiovascular system. Over the years, Dr. Marlene Grenon has studied the effects of microgravity on astronauts, who often suffer from circulatory issues after returning to Earth and increases the risk of heart attack as they age.

Dr. Grenon and colleagues, Dr. Sonja Schrepfer and Dr. Tobias Deuse, have found multiple factors influenced by the low gravity environment of space, including gene expression, cell function interference, and thinning vascular walls, which contribute to the declining cardiovascular health of astronauts. Similar issues are evident in normal gravity cardiovascular disease sufferers.

Although not a problem on ISS, as astronauts return to normal life on Earth, the effect on their health is detrimental(damaging) and long term. But Dr. Schrepfers team has discovered a molecule that may stop the thinning of vascular walls and hope to begin human trials soon.

Additionally, Dr. Schrepfer will be studying the effects of space on the human immune system similar to the work done by Dr. Millie Hughes-Fulford, whos been studying the subject since 2003.

Currently, Dr. Hughes-Fulford has been studying gene expression in T-cells. Her studies have found that in low gravity five different miRNAs (microRNA), normally responsible for activating the genes of T-cells, were not functioning. These alterations, normally seen in the elderly over a period of 30 years, starting in astronauts, typically at the height of health, after only 30 minutes in space.

So far, the only cell function researchers can find that is not negatively affected by time spent in space is the process by which DNA repairs itself. Dr. Faith Karouia of USCF and Dr. Honglu Wu of NASAs Johnson Space Center, have studied fibroblast cells from micro gravity environments compared to Earth bound cells and found no change despite the change in gravity or radiation.

Although more data is needed for a full conclusion, scientists hope the discovery can aid research into how cancer cells survive and self-heal through radiation treatment as well as help bolster astronaut health during space flight.

Overall, low-gravity healthcare is a multidisciplinary endeavor across many medical fields and is necessary to protect the long-term health of astronauts, especially as various agencies aim for deeper exploratory space travel. In addition, the same medical breakthroughs have the potential to improve medical care for the general population too significantly.

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