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Do Some Cancer Drugs Offer Hope for ALS Therapy? | ALZFORUM – Alzforum

By JoanneRUSSELL25

26 May 2017

Could tyrosine kinase inhibitors, a standard tool of cancer treatment, help people with amyotrophic lateral sclerosis? Converging evidence suggests that this drug class may slow ALS progression, perhaps through multiple mechanisms. In the May 24 Science Translational Medicine, researchers led by Haruhisa Inoue at Kyoto University, Japan, report that numerous different inhibitors of the tyrosine kinases Src and c-Abl improve the survival of motor neurons from ALS patients. The compounds act by stimulating autophagy, which accelerates the removal of toxic proteins. One of the most potent inhibitors, bosutinib, boosted motor neuron survival by 50 percent and modestly lengthened the lives of ALS model mice, the authorsreport.

In related news, researchers recently reported positive findings from a Phase 3clinical trial of another tyrosine kinase inhibitor, masitinib, at the European Network for the Cure of ALS (ENCALS) annual meeting, held May 18 to 20 in Ljubljana, Slovenia. This inhibitor, which is approved to treat tumors in animals but not people, reportedly doused neuroinflammation in the spinal cord. Patients on the drug maintained motor abilities four months longer than did those on placebo, a statistically significant improvement. AB Science in Paris, the manufacturer, has applied to the European Medicines Agency for approval to use the drug in people, and is planning to start another Phase 3trial this year before applying for approval from the U.S. Food and DrugAdministration.

The data suggest that tyrosine kinase inhibitors might help in other neurodegenerative diseases such as Alzheimers and Parkinsons, which also accumulate toxic proteins and cause neuroinflammation, said Charbel Moussa at Georgetown University, Washington, D.C. He noted that many of these compounds are already FDA-approved for other conditions, and can be used at much lower doses for neurodegenerative disease than for cancer. These drugs represent a promising alternative to antibody and vaccination strategies, he told Alzforum. He was not involved in either of thesestudies.

ALS in a Dish. Stem cells derived from people with familial ALS differentiate into neurons in culture that express motor neuron markers HB9, ChAt, and SMI-32. Nuclei are stained blue. [Courtesy of Science TranslationalMedicine/AAAS.]

The need for new drugs for ALS is immense. In this devastating disease, spinal motor neurons wither, robbing people of motor control and killing them typically within three to five years. Approved treatments are limited to riluzoleand edaravone, which was just approved in the U.S. this month (see May 2017 news). Both modestly slow functional decline, though efficacy data for edavarone remains sparse. Researchers are still seeking betteroptions.

To cast a wider net, Inoue and colleagues screened 1,416 compounds that are either approved for human use or in clinical trials. First author Keiko Imamura generated induced pluripotent stem cells (iPSCs) from a single ALS patient who carried a SOD1 mutation. The authors differentiated these cells into spinal motor neurons and cultured them for seven days, added the compounds, and assessed survival one week later. In this screen, 27 compounds boosted survival more than three standard deviations above that of untreated cells. Half of these compounds targeted the Src/c-Abl signaling pathway. These cytosolic tyrosine kinases participate in numerous cellular processes and are implicated in cancer. To confirm these enzymes mediated the drug effect, the authors knocked down Src and c-Abl with short interfering RNAs, and again saw improved motor neuronsurvival.

Among the hits, the authors selected bosutinib for follow up. This drug is approved to treat chronic myelogenous leukemia, directly inhibits Src and c-Abl, and acts at lower doses than the other compounds in the screen. Bosutinib normalized autophagy in the diseased motor neurons. Compounds that blocked autophagy weakened the protective benefits of bosutinib, suggesting this was its mechanism of action. In keeping with this, other known autophagy boosters, such as rapamycin, also improved motor neuron survival. As might be expected, revving up autophagy cleaned up deposits of misfolded, toxic SOD1. The authors did not detail how inhibition of Src and c-Abl stimulated autophagy, but other work provides clues. Moussa and colleagues have reported that c-Abl inhibition activates the ubiquitin ligase parkin, which then interacts with autophagy proteins such as beclin-1 to stimulate degradation of proteins including A and -synuclein (see Lonskaya et al., 2013; Lonskaya et al., 2014; Wenqiang et al., 2014). A sister compound to bosutinib, nilotinib, is currently in Phase 2 trials for PDand ADthat Moussa and colleagues at Georgetown are running (see Nov 2015 conference news).

Only 2 percent of people with ALS carry SOD1 mutations. What about other forms of the disease? To expand their study, the authors generated motor neurons from three ALS patients with TDP-43 mutations, three with C9ORF72 expansions, and three with sporadic disease. Most people with ALS, regardless of their mutation status, accumulate misfolded TDP-43, and C9ORF72 is the most common familial mutation. In this study, bosutinib lowered levels of misfolded TDP-43 and poly dipeptide repeats formed from the C9ORF72 expansion; it also improved survival in all cell lines save for one from a sporadiccase.

Next, the authors tested bosutinib in the SOD1-G93A mouse model of ALS. These animals become paralyzed at four and die by six months of age. The authors injected a single dose, 5 mg/kg/day, intraperitoneally for six weeks beginning at two months of age. Src and c-Abl activity in the spinal cord was cut in half, indicating target engagement. Treated mice accumulated slightly less misfolded SOD1 and had about three times as many surviving motor neurons in their spinal cords as untreated ones. Nevertheless, treatment delayed disease onset by only 11 days and extended survival by just eightdays.

Why didnt the drug work better in mice, given the promising in vitro data? Nonneuronal cells such as astrocytes contribute to ALS pathology, but Inoues screen did not test for effects of bosutinib on these cells (e.g. Oct 2014 news; Nov 2014 news). In an email to Alzforum, Inoue also suggested that bosutinib could be optimized to better enter the brain and avoid potential off-target effects. Peter Davies at the Feinstein Institute for Medical Research in Manhasset, New York, pointed out that tyrosine kinase inhibitors such as bosutinib are typically not specific for c-Abl. I would like to see pharma make more specific compounds, because then we would learn if the key factor really is c-Abl, rather than another kinase, and there would be fewer off-target effects, Davies wrote to Alzforum. He acknowledged that making specific c-Abl inhibitors is a challenging task, and that companies have tried and abandoned some past efforts for lack ofsuccess.

The findings from bosutinib and nilotinib complement those for masitinib. This veterinary drug seems to act mostly on immune cells. Preclinical studies suggested masitinib inhibits the tyrosine kinases CSF-1R and C-kit in microglia, macrophages, and mast cells, circulating white blood cells that trigger allergic and inflammatory reactions. In animal models, masitinib prevents microgliosis and astrogliosis in the spinal cord, as well as the infiltration of mast cells and macrophages into neuromuscular junctions (see Trias et al., 2016). This provides a rational basis for the protective effects of masitinib in delaying neuromuscular junction denervation. However, more research is needed to understand the detailed mechanism of action of the drug, Luis Barbeito at the Pasteur Institute of Montevideo, Uruguay, wrote to Alzforum. Barbeito presented preclinical data on masitinib atENCALS.

In the Phase 3 trial, 394 patients from nine countries took either 4.5 mg/kg masitinib, 3 mg/kg, or placebo for nearly a year. By prespecified plan, the researchers stratified participants into fast progressors (those who declined more than 1.1 point per month on the revised ALS Functional Rating Scale) and normal progressors. About 85 percent of the participants were normal progressors. Among this group, those taking 4.5 mg/kg masitinib declined 3.4 points less on the ALSFRS-R than the placebo group over the course of the study. This translated to 27 percent less functional decline over this time period, a clinically meaningful difference, according to Jesus Mora at Hospital Carlos III in Madrid, who presented the clinical trial findings at ENCALS. Treated participants maintained greater lung capacity and reported better quality of life than the placebo group. They lasted 20 months before their disease progressed nine points or more on the ALSFRS-R, compared with 16 months for those on placebo. Participants who took the lower 3 mg/kg dose also reported better quality of life, but their trend toward slower functional decline did not reachsignificance.

Other data hinted that the drug was most effective when given at an early stage of disease. When normal and fast progressors were combined, the 4.5 mg/kg dose only slowed decline in those who had had the disease for less than two years. Fast progressors may need earlier treatment, Morasuggested.

The safety profile was acceptable, with no surprises cropping up, the researchers said. The treatment group experienced more serious adverse events than the placebo group. These were scattered across different organ systems and did not fall into any pattern. For oncology use, tyrosine kinase inhibitors are normally given at higher doses, from 6 to 12 mg/kg, with no serious safety issues, the researchers noted.Madolyn BowmanRogers

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StemCyte renewed strategic partnership with the Neonatal Research Institute at Sharp Mary Birch Hospital for Women … – PR Newswire (press release)

By Sykes24Tracey

"The practice of helping babies by providing stem cells at birth has been around for a long time; it makes sense for the sickest infants," said Anup Katheria, MD, director of the Neonatal Research Institute. "We're focused on producing evidence that shows the benefits. We think this could become the foundation for practice-changing birthing techniques, transforming outcomes for the most critical of newborns nationwide."

As a California-based public/private cord blood banking company and with a strong research focus, StemCyte stands ready to help efficiently and effectively to support the partnership with Sharp HealthCare to educate expecting parents of their options, to ensure the information is delivered accurately and consistently, and to collect the cells in cord blood and process and store them with the highest quality standards in the industry.

"We are excited to work with the Sharp Mary Birch Neonatal Research Institute, and we are looking forward to maximizing the capacity for cord-blood banking. Residents of California and people around the world will benefit from the research and increased availability of umbilical cord blood stem cell transplant units." said Jonas C. Wang, Ph.D., CEO/ Chairman of StemCyte Group.

About StemCyte StemCyte's rich history started with a mission of being dedicated to helping the world's physicians save more lives by providing high quality, safe and effective stem cell transplantation and therapy to all patients in need. Located in the US, India and Taiwan, StemCyte has supplied over 2100 cord blood products for over 40 life-threatening diseases to over 300 leading worldwide transplant centers. StemCyte is actively involved in the development of stem cell therapies. StemCyte was the first to donate umbilical cord blood units (UCB) to Dr. Jaing of Chung Gung Memorial Hospital for his clinical trial to use UCB to treat and cure Beta Thalassemia. More excitingly is the work and accomplishments of Prof Wise Young, MD, PhD. Prof. Young has completed Phase II clinical trials on patients with chronic spinal cord injury with UCB and the results are extremely encouraging. StemCyte is chosen by the US Department of Health and Human Services to help establishing a public National Cord Blood Inventory. Its headquarters are located in Baldwin Park, CA. To learn more visit http://www.StemCyte.com.

For more information call 626.646.2500

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Over 40 U.S. National Laboratory Sponsored Experiments on SpaceX CRS-11 Destined for the International Space … – GlobeNewswire (press release)

By JoanneRUSSELL25

May 26, 2017 14:28 ET | Source: Center for the Advancement of Science in Space

Kennedy Space Center, FL, May 26, 2017 (GLOBE NEWSWIRE) -- The SpaceX Falcon 9 vehicle is slated to launch its 11thcargo resupply mission (CRS-11) to the International Space Station (ISS) no earlier than June 1, 2017 from Kennedy Space Center Launch Complex 39A. Onboard the Falcon 9 launch vehicle is the SpaceX Dragon spacecraft, which will carry more than 40 ISS U.S. National Laboratory sponsored experiments. This mission will showcase the breadth of research possible through the ISS National Laboratory, as experiments range from the life and physical sciences, Earth observation and remote sensing, and a variety of student-led investigations. Below highlights the investigations as part of the SpaceX CRS-11 mission:

ADVANCED COLLOIDS EXPERIMENT-TEMPERATURE CONTROLLED-6 (ACE-T-6)

Matthew Lynch, Procter & Gamble (West Chester, OH)

Implementation Partner: NASA Glenn Research Center and Zin Technologies, Inc.

Colloids are suspensions of microscopic particles in a liquid, and they are found in products ranging from milk to fabric softener. Consumer products often use colloidal gels to distribute specialized ingredients, for instance droplets that soften fabrics, but the gels must serve two opposite purposes: they have to disperse the active ingredient so it can work, yet maintain an even distribution so the product does not spoil. Advanced Colloids Experiment-Temperature-6 (ACE-T-6) studies the microscopic behavior of colloids in gels and creams, providing new insight into fundamental interactions that can improve product shelf life.

EFFICIENCY OF VERMICOMPOSTING IN A CLOSED SYSTEM (NANORACKS-NDC-BMS-VERICOMPOSTING)

Bell Middle School (Golden, CO)

Implementation Partner: NanoRacks

Vermicomposting, or using worms to break down food scraps, is an effective way to reduce waste and obtain a nutrient-rich fertilizer for plants. The NanoRacks-NDC-Bell Middle School-Efficiency of Vermicomposting in a Closed System (NanoRacks-NDC-BMS-Vermicomposting) investigation is a student-designed project that studies whether red wiggler worms, a species of earthworm, are able to produce compost in space. Results are used to study the potential for composting as a form of recycling on future long-duration space missions.

FUNCTIONAL EFFECTS OF SPACEFLIGHT ON CARDIOVASCULAR STEM CELLS (CARDIAC STEM CELLS)

Dr. Mary Kearns-Jonker, Loma Linda University (Loma Linda, CA)

Implementation Partner: BioServe Space Technologies

Functional Effects of Spaceflight on Cardiovascular Stem Cells (Cardiac Stem Cells) investigates how microgravity alters stem cells and the factors that govern stem cell activity, including physical and molecular changes. Spaceflight is known to affect cardiac function and structure, but the biological basis for this is not clearly understood. This investigation helps clarify the role of stem cells in cardiac biology and tissue regeneration. In addition, this research could confirm the hypothesis that microgravity accelerates the aging process.

MULTIPLE USER SYSTEM FOR EARTH SENSING (MUSES)

Paul Galloway, Teledyne Brown Engineering (Huntsville, AL)

Implementation Partner: Teledyne Brown Engineering

Teledyne Brown Engineering developed the Multiple User System for Earth Sensing (MUSES), an Earth imaging platform, as part of the companys new commercial space-based digital imaging business. MUSES hosts earth-viewing instruments (Hosted Payloads), such as high resolution digital cameras, hyperspectral imagers, and provides precision pointing and other accommodations. It hosts up to four instruments at the same time, and offers the ability to

change, upgrade, and robotically service those instruments. It also provides a test bed for technology demonstration and technology maturation by providing long-term access to the space environment on the ISS.

NANORACKS-JAMSS-2LAGRANGE-1

Tomohiro Ichikawa, Lagrange Corp. (Tokyo, Japan)

Implementation Partner: NanoRacks

Spaceflight affects organisms in a wide range of ways, from a reduction in human bone density to changes in plant root growth. NanoRacks-JAMSS-2 Lagrange-1 helps students understand potential spaceflight-related changes by exposing plant seeds to microgravity, and then germinating and growing them on Earth. The plants are compared with specimens grown from seeds that remained on the ground. The investigation also connects students to the space program by sending their photographic likenesses and personal messages into orbit. This connection inspires the next generation of scientists and engineers who will work on international space programs.

NEUTRON CRYSTALLOGRAPHIC STUDIES OF HUMAN ACETYLCHOLINESTERASE FOR THE DESIGN OF ACCERERATED REACTIVATORS (ORNL-PCG)

Dr. Andrey Kovalevsky, Oak Ridge National Laboratory (Oak Ridge, TN)

Implementation Partner: CASIS

The investigative team is trying to improve our understanding of acetylcholinesterase, an enzyme essential for normal communication between nerve cells and between nerve and muscle cells. As a target of deadly neurotoxins produced by animals as venom or by man as nerve agents and pesticides, understanding the structure of acetylcholinesterase is critical to designing better antidotes to poisoning by chemicals that attack the nervous system. The Oak Ridge National Lab team plans to use the microgravity environment of space to grow large crystals of the enzyme that will be imaged back on Earth using a powerful imaging approach called neutron diffraction. Neutron diffraction yields very detailed structural information but requires much larger crystals than traditional x-ray diffraction imaging methods. The investigators hypothesize that structural images of space-grown crystals will bring us closer to more effective and less toxic antidotes for neurotoxins that bind and inhibit acetylcholinesterase.

STUDENT SPACEFLIGHTS EXPERIMENT PROGRAM MISSION 10

Dr. Jeff Goldstein, National Center for Earth and Space Science Education (Washington, D.C.)

Implementation Partner: NanoRacks

The Student Spaceflight Experiments Program (SSEP) provides one of the most exciting educational opportunities available: student-designed experiments to be flown on the International Space Station. The NanoRacks-National Center for Earth and Space Science Education-Odyssey (NanoRacks-NCESSE-Odyssey) investigation contains 24 student experiments, including microgravity studies of plant, algae and bacterial growth; polymers; development of multi-cellular organisms; chemical and physical processes; antibiotic efficacy; and allergic reactions. The program immerses students and teachers in real science, providing first-hand experience conducting scientific experiments and connecting them to the space program.

SYSTEMIC THERAPY OF NELL-1 FOR OSTEOPOROSIS (RODENT RESEARCH-5)

Dr. Chia Soo, University of California at Los Angeles (Los Angeles, CA)

Implementation Partner: NASA Ames Research Center and BioServe Space Technologies

Astronauts living in space for extended durations experience bone density loss, or osteoporosis. Currently, countermeasures include daily exercise designed to prevent bone loss from rapid bone density loss deterioration. However, in space and on Earth, therapies for osteoporosis cannot restore bone that is already lost. The Systemic Therapy of NELL-1 for Osteoporosis (Rodent Research-5) investigation tests a new drug on rodents that can both rebuild bone and block further bone loss, improving health for crew members in orbit and people on Earth. Dr. Soos laboratory has been funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases within the National Institutes of Health. This experiment builds on those previous research investigations.

THE EFFECT OF MICROGRAVITY ON TWO STRAINS OF BIOFUEL PRODUCING ALGAE WITH IMPLICATIONS FOR THE PRODUCTION OF RENEWABLE FUELS IN SPACE-BASED APPLICATIONS

Chatfield High School (Littleton, CO)

Implementation Partner: NanoRacks

Algae can produce both fats and hydrogen, which can each be used as fuel sources on Earth and potentially in space. NanoRacks-National Design Challenge-Chatfield High School-The Effect of Microgravity on Two Strains of Biofuel Producing Algae with Implications for the Production of Renewable Fuels in Space Based Applications (NanoRacks-NDC-CHS-The Green Machine) studies two algae species to determine whether they still produce hydrogen and store fats while growing in microgravity. Results from this student-designed investigation improve efforts to produce a sustainable biofuel in space, as well as remove carbon dioxide from crew quarters.

TOMATOSPHERE-II

Ann Jorss, First the Seed Foundation (Alexandria, VA)

Implementation Partner: CASIS

Tomatosphere is a hands-on student research experience with a standards-based curriculum guide that provides students the opportunity to investigate, create, test, and evaluate a solution for a real world case study. Tomatosphere provides information about how spaceflight affects seed and plant growth and which type of seed is likely to be most suitable for long duration spaceflight. It also exposes students to space research, inspiring the next generation of space explorers. It is particularly valuable in urban school settings where students have little connection to agriculture. In its 15-year existence, the program has reached approximately 3.3 million students.

VALLEY CHRISTIAN HIGH SCHOOL STUDENT EXPERIMENTS

Valley Christian High School (San Jose, CA), in partnership with other high schools throughout the world

Implementation Partner: NanoRacks

Students at Valley Christian High School (VCHS) have a rich history of sending investigations to the ISS through its launch partner, NanoRacks. On SpaceX CRS-11, students from VCHS have partnered with other students from across the world to send 12 total experiments to the ISS National Laboratory. Investigations will range from investigating high quality food nutrients, to the fermentation of microbes, to even an investigation monitoring the growth of a special bacterial strain. The program VCHS has developed with NanoRacks allows students the opportunity to not only conceive a flight project, but learn, understand, and implement the engineering required for a successful experiment in microgravity.

Thus far in 2017, the ISS National Lab has sponsored over 75 separate experiments that have reached the station. This launch manifest adds to an impressive list of experiments from previous missions in 2017 to include; stem cell studies, cell culturing, protein crystal growth, external platform payloads, student experiments, Earth observation and remote sensing. To learn more about those investigations and other station research, visit http://www.spacestationresearch.com.

# # #

About CASIS: The Center for Advancement of Science in Space (CASIS) is the non-profit organization selected to manage the ISS National Laboratory with a focus on enabling a new era of space research to improve life onEarth. In this innovative role, CASIS promotes and brokers a diverse range of research inlife sciences,physical sciences,remote sensing,technology development,andeducation.

Since 2011, the ISS National Lab portfolio has included hundreds of novel research projects spanning multiple scientific disciplines, all with the intention of benefitting life on Earth.. Working together with NASA, CASIS aims to advance the nations leadership in commercial space, pursue groundbreaking science not possible on Earth, and leverage the space station to inspire the next generation.

About the ISS National Laboratory: In 2005, Congress designated the U.S. portion of the International Space Station as the nation's newest national laboratory to maximize its use for improving life on Earth, promoting collaboration among diverse users, and advancing STEM education. This unique laboratory environment is available for use by other U.S. government agencies and by academic and private institutions, providing access to the permanent microgravity setting, vantage point in low Earth orbit, and varied environments of space.

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Over 40 U.S. National Laboratory Sponsored Experiments on SpaceX CRS-11 Destined for the International Space ... - GlobeNewswire (press release)

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Stranger saves life of woman with stem cell transplant – FOX31 Denver

By LizaAVILA


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Stranger saves life of woman with stem cell transplant
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DENVER -- This is a terrible statistic. Eighty percent of blood cancer patients in need of stem cell or bone marrow transplant are not able to get one, in part because they can't find a match. But you can help change that and save a life by registering ...

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Baldness treatment discovered at UCSF – The Mercury News

By JoanneRUSSELL25

The late actor Telly Savalas said it best: Were all born bald, baby.

And bald CAN be beautiful.

But for many follicly-challenged folks, news out of UC San Francisco this week offers some hope of finally having a bad hair day.

In experiments in mice, researchers there have discovered that regulatory T cells (Tregs; pronounced tee-regs), a type of immune cell associated with controlling inflammation, directly trigger stem cells in the skin to promote healthy hair growth.

Without these immune cells as partners, the researchers found, the stem cells cannot regenerate hair follicles, leading to baldness.

Our hair follicles are constantly recycling: when a hair falls out, the whole hair follicle has to grow back, said Dr. Michael Rosenblum, an assistant professor of dermatology at UCSF and senior author on the new paper.

This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential. If you knock out this one immune cell type, hair just doesnt grow.

In other words: no Tregs, no tresses.

The new study appeared online Friday in Cell, a journal that publishes peer-reviewed articles reporting findings of unusual significance in any area of experimental biology.

For 35 million U.S. men and 21 million women who are experiencing hair loss, according to Statistic Brain Research Institute,the UCSF report would probably qualify as significant.

The study suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that causes hair loss, and could potentially play a role in other forms of baldness, including male pattern baldness, Rosenblum said.

And since the same stem cells are responsible for helping heal the skin after injury, the researchers note, the study raises the possibility that Tregs may play a key role in wound repair as well.

Normally, the researchers say, Tregs act as peacekeepers and diplomats, informing the rest of the immune system of the difference between friend and foe. When Tregs dont function properly, people may develop allergies to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the bodys own tissues.

Like other immune cells, most Tregs reside in the bodys lymph nodes, but some live permanently in other tissues, where researcher say they seem to have evolved to assist with local metabolic functions as well as playing their normal anti-inflammatory role. In the skin, for example, Rosenblum and colleagues have previously shown that Tregs help establish immune tolerance to healthy skin microbes in newborn mice, and these cells also secrete molecules that help heal wounds into adulthood.

Rosenblum wanted to better understand the role of these resident immune cells in skin health. To do this, he and his team developed a technique for temporarily removing Tregs from the skin. But when they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery.

We quickly noticed that the shaved patches of hair never grew back, and we thought, Hmm, now thats interesting, Rosenblum said. We realized we had to delve into this further.

The researchers including UCSF postdoctoral fellow and first author Niwa Ali believe a betterunderstanding of Tregs critical role in hair growth could lead to improved treatments for hair loss more generally and have implications for alopecia areata, an autoimmune disease that causes patients to lose hair in patches from their scalp, eyebrows, and faces.

For many other baldly confident folks, however, Fridays findings may just warrant a shrug.As they say, No hair, dont care.

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UW Health trial involves injecting stem cells into patients with heart failure – Channel3000.com – WISC-TV3

By Sykes24Tracey

UW Health trial involves injecting... More Headlines

MADISON, Wis. - Doctors at UW Health are involved in a clinical trial using stem cells for the treatment of heart failure.

The CardiAMP therapy involves withdrawing a patients bone marrow. The bone marrow is then processed on-site to separate the stem cells from the plasma. The patients own stem cells are then injected into damaged areas of the heart using a catheter.

It is hopeful that we can improve things. I dont think we can necessarily cure the damage, but I think we can improve things, said Dr. Amish Raval, director of cardiovascular clinical research at UW Health.

The CardiAMP Heart Failure Trial is a phase III study that will eventually enroll up to 260 patients. For the first 10 patients, UW Health is one of three sites nationwide performing the procedure.

I figured it was possibly going to do something good for me, said Dan Caulfield, a Madison man enrolled in the study.

Caulfield, who is 81 years old, has had three heart attacks.

I was 46 years old and had a heart attack. It was called a fatal heart attack in those days, Caulfield said. I had two more heart attacks in 2002, and since then it has been sort of downhill.

Improving the quality of life of individuals with heart failure is a goal of the CardiAMP therapy.

There is about a 50 percent five-year mortality associated with this condition and those five years can be awfully tough on these folks because they have a lot of problems with shortness of breath, weakness and sometimes chest discomfort while walking. So it is not just a matter of quantity of life, it is also a quality of life issue, Raval said.

The procedure involves a very targeted injection of stem cells into the area near where the heart is damaged.

We create a targeted map and based on that targeted map we have a really clear sense of where the damage is. Then it is my task to go in and try to get into the adjacent border areas, Raval said.

In the U.S. there are approximately 6.5 million people living with heart failure. According to the American Heart Association, that number is expected to rise by 46 percent by the year 2030.

This is one of the few pivotal trials in the United States that is really, I think, going to pave the way for future studies, Raval said.

The outcome of the CardiAMP trial will be measured by any change in distance during a six-minute walk 12 months after an initial baseline measurement is taken.

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New baldness cause accidentally discovered by scientists could lead to hair loss treatment – The Independent

By raymumme

A new cause of baldness has been accidentally discovered by scientists in the US in a breakthrough that could help develop a way to regrow hair.

The researchers were investigating the role played by anti-inflammatory immune cells called Tregs in skin health generally.

They found a way to temporarily remove the Tregs from the skin of laboratory mice, who had been shaved to allow the effects to be observed.

But the scientists then noticed something unexpected the hairfailed to grow back.

Previously it was thought that stem cells cause hairs to regrow after they fall out, but the team discoveredthat this only happens if Tregs are present.

One of the scientists, Professor Michael Rosenblum, an immunologist and dermatologist at University of California San Francisco, said: Our hair follicles are constantly recycling. When a hair falls out, the whole hair follicle has to grow back.

This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential.

If you knock out this one immune cell type, hair just doesn't grow.

Its as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work.

The stem cells rely on the Tregs completely to know when it's time to start regenerating.

The researcher believe that defects in Tregs could be responsible for the immune disease, alopecia areata, which causes hair to fall out in patches and possibly also play a part in other kinds of baldness.

The same stem cells that regrow hair are also involved in healing damage to the skin, so Tregs may also be involved in this process.

Tregs role as previously understood was mainly to regulate the immune system, helping it tell what to attack and what to leave alone.

When they malfunction it can lead to allergies to peanuts and other harmless substances or cause the immune system to attack the body.

Professor Rosenblum and colleagues had previously showed that Tregs help the immune systems of baby mice learn which skin microbes are not harmful and also that they secrete molecules that help heal wounds.

They were investigating these effects further when they noticed that patches of shaved hair on the lab mice were not regrowing.

We thought, Hmm, now thats interesting, Professor Rosenblum said. We realised we had to delve into this further.

Using sophisticated imaging techniques, the researchers were able to show that Tregs gathered around follicle stem cells at the start of the process to regrow a hair.

When Tregs were removed from the skin, this prevented the regrowth of hair but only if this was done within three days of the hair being shaved. After this time, the hair would regrow normally despite the absence of Tregs.

The cause of alopecia is poorly understood, but previous studies have showed genes associated with the condition are mostly related to Tregs. Boosting Treg function has been found to help.

Professor Rosenblum suggested further research into Tregs role could lead to improved treatments for hair loss generally and better understanding of their role in wound healing.

We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after it's damaged, he said.

But what we found here is that stem cells and immune cells have to work together to make regeneration possible.

The research was described in the journal Cell.

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New baldness cause accidentally discovered by scientists could lead to hair loss treatment - The Independent

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Stem cell ‘plaster’ could help heart failure patients – The Christian Institute

By Sykes24Tracey

The new research showed that adult stem cells could help beat heart failure.

A sticking plaster made from adult stem cells could be a significant step towards combatting heart failure, scientists say.

Researchers discovered that stem cells taken from a patients thigh and transplanted onto the heart led to improved heart function after one year.

Heart failure is thought to affect between 500,000 to 900,000 people in the UK. It occurs when the heart becomes too weak to efficiently pump blood around the body.

The authors of the study, published in the Journal of the American Heart Association, said the therapy was potentially a long-term solution to the problem.

They said that, promising results in the safety and functional recovery warrant further clinical follow-up and larger studies, which they hope will confirm the treatments potential.

Professor Metin Avkiran, associate medical director at the British Heart Foundation, hailed the exciting breakthrough.

He said: Heart failure is a cruel and debilitating illness affecting more than half a million people across the UK. Currently, heart failure is incurable, but stem cell-based treatments may offer new hope to people suffering from the disease.

He echoed the call for further research, saying: The study involved only a small number of patients. In order to establish the long-term safety and benefits of the exciting new treatment we would need larger studies.

Heart failure often leaves sufferers struggling for breath and exhausted while carrying out simple everyday tasks, such as eating or getting dressed.

It can be caused by several issues including heart disease, diabetes and high blood pressure, but can also be the result of an unhealthy lifestyle.

Earlier this month, it was revealed that a remarkable new technique allows adult stem cells to be used to treat burn victims.

Taking a sample of skin stem cells and spraying them onto a victims burn caused new layers of skin to form over the burn, potentially healing even severe burns within weeks.

And in January, scientists released findings showing that synthetic cardiac stem cells could be used to treat patients who had suffered a heart attack by repairing the heart muscle damage.

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Medical Q&A: Progress made in getting stem cells to ‘take’ in mice – Sarasota Herald-Tribune

By Sykes24Tracey

Q: How close are we to curing blood diseases with human stem cells?

A: New research has nudged scientists closer to one of regenerative medicine's holy grails: the ability to create customized human stem cells capable of forming blood that would be safe for patients.

Advances reported in the journal Nature could not only give scientists a window on what goes wrong in such blood cancers as leukemia, lymphoma and myeloma. They could also improve the treatment of those cancers, which affect some 1.2 million Americans.

While the use of blood-making stem cells in medicine has been common since the 1950s, it remains pretty crude. After patients with blood cancers have undergone powerful radiation and chemotherapy, they often need a bone-marrow transplant to rebuild their white blood cells, which are destroyed by that treatment.

The blood-making stem cells that reside in a donor's bone marrow and in umbilical cord blood harvested after a baby's birth are called "hematopoietic," and they can be life-saving. But even these stem cells can bear the distinctive immune system signatures of the person from whom they were harvested. So they can provoke an attack if the transplant recipient's body registers the cells as foreign.

This response, called graft-versus-host disease, affects as many as 70 percent of bone-marrow transplant recipients soon after treatment, and 40 percent develop a chronic version of the affliction later. It kills many patients.

Rather than hunt for a donor who's a perfect match, doctors would like to use a patient's own cells to engineer the hematopoietic stem cells.

The patient's mature cells would be "reprogrammed" to their most primitive form: stem cells capable of becoming virtually any kind of human cell. Then factors in their environment would coax them to become stem cells capable of giving rise to blood.Once reintroduced into the patient, the cells would take up residence without prompting rejection and set up a lifelong factory of healthy new blood cells.

If the risk of rejection could be eliminated, physicians might also feel more confident treating blood diseases that are not immediately deadly such as sickle cell disease and immunological disorders with stem cell transplants.

One of two research teams, led by stem cell pioneer Dr. George Q. Daley of Harvard Medical School and the Dana Farber Cancer Institute, started their experiment with human "pluripotent" stem cells primitive cells capable of becoming virtually any type of mature cell.

The scientists then programmed those pluripotent stem cells to become endothelial cells, which line the inside of certain blood vessels.Using suppositions gleaned from experiments with mice, Daley said his team confected a "special sauce" of proteins that sit on a cell's DNA and program its function. When they incubated the endothelial cells in the sauce, they began producing hematopioetic stem cells.

Daley's team then transferred the resulting blood-making stem cells into the bone marrow of mice to see if they would "take." In two out of five mice who got the most promising cell types, they did. Not only did the stem cells establish themselves, they continued to renew themselves while giving rise to a wide range of blood cells.

A second team, led by researchers from Weill Cornell Medicine's Ansary Stem Cell Institute, achieved a similar result using stem cells from the blood-vessel lining of adult mice.

But Daley cautioned that significant hurdles remain before studies like these will transform the treatment of blood diseases.

"We do know the resulting cells function like blood stem cells, but they still are at some distance, molecularly, from native stem cells," he said.

Melissa Healy, Los Angeles Times

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‘It has been a long few days’: Jonathan Pitre on medical roller-coaster – Canoe

By daniellenierenberg

Andrew Duffy, Postmedia Network May 23, 2017

, Last Updated: 5:01 PM ET

Jonathan Pitre has been on a medical roller-coaster in the week since blood tests revealed that his stem cell transplant has taken root in his bone marrow.

While his white blood cell count has soared its now well within the normal range he has also suffered a series of complications that have severely tested his physical endurance.

It has been a long few days, said his mother, Tina Boileau. Hes been through hell.

Pitre, 16, is battling liver, kidney and gastrointestinal problems.

He has been diagnosed with typhlitis, a serious inflammation in part of his large intestine, that brings with it risk of a bowel perforation. He has undergone a series of x-rays and ultrasounds to check for perforations, all of which have come back negative.

At the same time, Pitre is fighting a liver infection that has caused his fever to spike, and his skin to yellow. His blood pressure has fluctuated, and his kidneys are struggling to process all of the fluids and medications that have been been pumped into his body. He hasnt been allowed to eat or drink for days to protect his damaged gastrointestinal system.

Pitre will undergo surgery Wednesday to have another central line installed so that he can be fed intravenously rather than through his existing g-tube, which sends nutrition directly to his stomach.

All of the complications have made it difficult to deliver enough medication to control Pitres pain levels, his mother said.

Its got to get better, she said.

Boileau is placing her faith in her sons new immune system, which has been rebuilt with the help of her donated stem cells. His white blood cell count is at 6.7 which is amazing, she said. And hopefully, that helps him fight everything hes going through.

A normal white blood cell count ranges from 4.0 to 11.

Pitre found out last Tuesday that the white blood cells in his system were all donor cells, which signalled that his transplant had successfully engrafted in his bone marrow. Bone marrow stem cells produce most of the bodys blood, including the white blood cells that are responsible for fighting bacteria, viruses and other pathogens.

Pitres lead physician, Dr. Jakub Tolar, said last week that the Russell teenager remains extremely fragile and susceptible to all kinds of complications. But Tolar also said the success of the transplant has established the pre-condition for his recovery.

It has now been 40 days since Pitre was infused with stem cells drawn from his mothers hip bone at the University of Minnesota Masonic Childrens Hospital.

In the next three months, doctors will be on the lookout for signs of acute graft-versus-host-disease (GVHD), a complication in which the donors white blood cells turn on the patients tissues and attack them as foreign. Last week, Pitre showed signs of a rash which can sometimes be a telltale sign of the disease, but a skin biopsy showed that the problem was not related to GVHD.

Anyone who receives stem cells from another person is at risk of developing the condition, which can range from mild to life-threatening. It commonly affects the skin, liver or gastrointestinal tract.

Pitre suffers from a severe form of epidermolysis bullosa (EB), a painful and progressive skin disease that has inflicted deep, open wounds on his body.

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Researchers identify ‘signal’ crucial to stem cell function in hair follicles – Medical Xpress

By LizaAVILA

May 24, 2017 by Collene Ferguson Jeff Biernaskies research identifies a factor essential for dermal stem cells to continuously divide during tissue regeneration. Credit: Riley Brandt, University of Calgary

Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

Jeff Biernaskie's research, published recently in the scientific journal npj Regenerative Medicine identifies a key signalling protein called platelet-derived growth factor (PDGF). This protein is critical for driving self-renewal and proliferation of dermal stem cells that live in hair follicles and enable their unique ability to continuously regenerate and produce new hair.

"This is the first study to identify the signals that influence hair follicle dermal stem cell function in your skin," says Biernaskie, an associate professor in comparative biology and experimental medicine at the University of Calgary'sFaculty of Veterinary Medicine, and Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. Biernaskie is also a member of the Alberta Children's Hospital Research Institute.

"What we show is that in the absence of PDGF signalling hair follicle dermal stem cells are rapidly diminished because of their inability to generate new stem cells and produce sufficient numbers of mature dermal cells within the hair follicle."

Biernaskie and his team of researchers study dermal stem cells located within hair follicles. They are looking to better understand dermal stem cell function and find ways to use these cells to develop novel therapies for improved wound healing after injury, burns, disease or aging.

This study, co-authored byRaquel Gonzalez and Garrett Moffatt,shows that PDGF is key to maintaining a well-functioning stem cell population in skin. And in normal skin, if you don't have enough of it the stem cell pools start to shrink, meaning eventually the hair will no longer grow and wounds will not heal as well.

"It's an important start in terms of how we might modulate these cells towards developing future therapies that could regenerate new dermal tissue or maintain hair growth" says Biernaskie.

Biernaskie's lab is looking at the potential role of stem cells in wound healing and the potential to stimulate these cells to improve skin regeneration, as opposed to forming scars.

Explore further: Using stem cells to grow new hair

More information: Raquel Gonzlez et al. Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal, npj Regenerative Medicine (2017). DOI: 10.1038/s41536-017-0013-4

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Researchers identify 'signal' crucial to stem cell function in hair follicles - Medical Xpress

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‘Signal’ Crucial to Stem Cell Function in Hair Follicles Identified – Technology Networks

By daniellenierenberg

Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

Jeff Biernaskies research, published recently in the scientific journal npj Regenerative Medicine identifies a key signalling protein called platelet-derived growth factor (PDGF). This protein is critical for driving self-renewal and proliferation of dermal stem cells that live in hair follicles and enable their unique ability to continuously regenerate and produce new hair.

This is the first study to identify the signals that influence hair follicle dermal stem cell function in your skin, says Biernaskie, an associate professor in comparative biology and experimental medicine at the University of Calgary's Faculty of Veterinary Medicine, and Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. Biernaskie is also a member of the Alberta Childrens Hospital Research Institute.

What we show is that in the absence of PDGF signalling hair follicle dermal stem cells are rapidly diminished because of their inability to generate new stem cells and produce sufficient numbers of mature dermal cells within the hair follicle.

Biernaskie and his team of researchers study dermal stem cells located within hair follicles. They are looking to better understand dermal stem cell function and find ways to use these cells to develop novel therapies for improved wound healing after injury, burns, disease or aging.

This study, co-authored by Raquel Gonzalez and Garrett Moffatt, shows that PDGF is key to maintaining a well-functioning stem cell population in skin. And in normal skin, if you dont have enough of it the stem cell pools start to shrink, meaning eventually the hair will no longer grow and wounds will not heal as well.

Its an important start in terms of how we might modulate these cells towards developing future therapies that could regenerate new dermal tissue or maintain hair growth says Biernaskie.

Biernaskies lab is looking at the potential role of stem cells in wound healing and the potential to stimulate these cells to improve skin regeneration, as opposed to forming scars.

The research is funded by a grant from Canadian Institutes for Health Research (CIHR) and the Calgary Firefighters Burn Treatment Society.

This article has been republished frommaterialsprovided bythe University of Calgary. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Trendy Skin Care Ingredients Are Being Added to Hair Care Products – Allure Magazine

By daniellenierenberg

Beauty elicits a deep, instinctive need to share from an early age. In fact, we defy you to find a more generous creature than a 7-year-old with a sparkly, new lip gloss in her backpack. Cooties be damned, she will prettify every second grader in sight. And we get it: weve built careers on swapping beauty secrets (and, okay, maybe a gloss or two).

We see this same communal spirit, shall we say, within the industry. Across brands and categories, this borrowing of ideas and technologies sparks trends and spawns knock-offs. In 2017, cosmetic ingredients flow freely, breaking all boundaries: Those once reserved for creams find their way into compacts . The same earthy clay and charcoal that purify pores can also whiten teeth and degrease roots.

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And were all for spreading the love when the science is legit. But the latest take-over hair-care companies co-opting buzzy skin-care actives, like peptides, stem cells, and antioxidants has us questioning just how translatable such technology truly is. Are we going too far in attempting to anti-age and revitalize something thats technicallydead?

Because, facts, after all: While skin and hair are composed of similar proteins and fats, living (innervated, blood-perfused) skin cells are in a constant state of renewal, rising up, plump and fresh, from the basal layer before eventually flattening out and sloughing off, says cosmetic chemist Randy Schueller . When injured or damaged, skin has the capacity to heal itself through normal biological processes, adds cosmetic chemist Jim Hammer . Hair, on the other hand, is dead at least the grown-out lengths of which we see and style and twirl. Hairs only vital part is nestled deep within the scalp: The cells of the hair follicles reproduce rapidly, pushing out hair fibers in the process, explains Melissa Piliang, a dermatologist at the Cleveland Clinic. But once sprouted from the scalp, those strands possess no living cells or repair mechanisms.

These distinctions have long dictated product goals: Skin care aims to affect biological processes, such as boosting cell turnover, increasing collagen synthesis, and inhibiting pigment production, says cosmetic chemist NiKita Wilson. Knowing this, we obsess over penetration can those actives actually get into the skin to do their good work? and chemists devise deep-diving delivery systems and penetration enhancers to guarantee performance. For hair, there really isnt much that can be done on a biological front short of improving the condition of the scalp to promote healthier strands, adds Wilson. It makes sense, then, that the majority of hair potions are designed to work on the surface, moisturizing and sealing hair to make it glassy, smooth, and full, while minimizing friction and breakage. While certain perfectly sized and shaped hydrators and proteins can seep past the hairs outer cuticle layer, into the deeper cortex, says Wilson, their effect is short-lived. Only chemicals like hair dyes and relaxers can alter hair in a lasting way.

So what of these new skin-inspired #hairgoals were hearing about, like anti-aging, anti-pollution, and high-tech hydration? Most of this is marketing driven with maybe a kernel of truth underneath, says Schueller. That kernel could be a single lab test showing a specific active, when dripped on cells in a glass dish, has some sort of effect which, by the way, doesnt mean it will work when delivered in final products on real people, he notes. Or perhaps a company finds a common water contaminant causes some degree of hair damage and then concocts an antioxidant to combat it. Even if the trauma to hair is miniscule compared to ordinary wear and tear, theyve now got enough data to make an antipollution claim and a new line of products to go with it, Schueller says. Across beauty lines, science sells: How do you make hair care more innovative? By using skin-care ingredients that elevate the level of sophistication, says cosmetic chemist Ginger King.

A successful tactic, judging from the proliferation of skin-inspired shampoos and serums on shelves, real and virtual. But why are we so eager to buy? Our population is aging, of course; yearning to maintain a healthy appearance, to look as young as we feel, says psychologist and marketing consultant Vivian Diller, PhD. Any product that promotes youth, well being, and vitality will be enormously appealing.

According to Rachel Anise, a communication studies professor at Golden West College in Huntington Beach, CA, there may also be social-psychology constructs at work here. People, on the whole, are largely swayed by what she calls the halo effect: We see stem cells, for example, as good at a basic level, and thereby extend their goodness to everything else in which they may be included, even if that reasoning is fundamentally flawed. And then theres the way we process advertising claims, she says, quickly and effortlessly, without thinking critically about them. Instead of questioningif or whyantioxidants may work on hair as they do skin, we'll just see a model with beautiful hair, acknowledge from past experience that antioxidants benefit skin, and automatically make the connection in two seconds, no less that they'll give our hair a youthful edge as well, says Anise.

Lucky for you, beauty analysis is sort of our jam. Here, we reality-check three adapted-for-hair-care claims:

THE CLAIM: Slowing down the aging process

WHAT IT MEANS FOR HAIR: The way hair ages has a lot to do with genetics and overall health, says dermatologist Lindsey Bordone. Hair tends to become finer over time as follicles miniaturize after menopause, she adds. It may turn coarse and brittle, and as pigment production wanes, fade to gray. On the scalp, cell turnover slows, giving rise to oil and flakes. UV rays a main cause of skin aging can degrade hairs proteins and color, but youd need a lot of concentrated sun exposure for that to be a real problem, says Schueller.

WHAT WORKS: Collagen and elastin proteins can cling to hairs surface, plumping and softening but only until your next shampoo. Plant-based stem cells essentially serve as antioxidants, curbing free radical damage, but their ability to thicken hair (or skin for that matter) is largely unproven. Surprisingly, peptides, which rev up collagen production, do show promise for aging hair. On the face, they plump skin to delay wrinkles and sagging. When applied to the scalp in a leave-on formula, they aid in anchoring the follicles to help strands remain firmly planted for a thicker head of hair, says Wilson. According to dermatologist Jeannette Graf , peptides are especially beneficial for thinning hair, which results from weakened scalp skin and circulation. Alongside peptides, she suggests looking for essential oils of lavender, orange, sage, and lemon peel to improve microcirculation, and enhance the delivery of nutrients to the hair bulb for healthier strands. As for sun care, hats trump UV filters. Think about how much sunscreen you need to put on skin to truly protect it, Schueller says. Its the same for hair and scalp: Youd need a tremendous amount, and whos going to apply that heavy of a coating?

THE CLAIM: Combatting pollution

WHAT IT MEANS FOR HAIR: Every day, our hair, like our skin, is exposed to free radical-inciting pollutants in the air and water. According to dermatologist Michelle Henry, all types of pollution, including particulate matter, dust, smoke, nickel, lead, and sulfur dioxide and nitrogen dioxide [emitted from vehicles and power plants] can settle on the scalp and hair causing significant inflammation, dryness, dullness, even hair loss.If that werent devastating enough, ground-level smog, which contains high levels of ozone, can bleach our hair color, says Hammer. Other contaminants may rob it completely: Premature graying is seen more in smokers than non-smokers as a result of oxidative stress, says dermatologist Nicole Rogers, adding that free radicals from all sources not just cigarettes can affect the follicles' ability to repigment. That said, pollutions precise toll on hair is unknown. I havent seen a ton of research proving its a major threat, says Schueller. Of all the things that can harm hair chemicals, brushing, heat Id imagine free radicals are low on the list.

WHAT WORKS: With thinning and graying as potential consequences, why take chances? While only a diet rich in free radical-quelching antioxidants can truly defend hair at a follicular level, certain products and practices can help safeguard strands from the environment. For starters, washing your hair thoroughly, and with sufficient frequency for your hair type, is key to curbing the scalp inflammation that contributes to hair loss, says Henry.Shampoos with chelating agents, like EDTA, will gently extract heavy metals (found in car exhaust, cigarette smoke, hard water). Youll also want to look for leave-ins with concentrated doses of antioxidants (think: vitamins, tea extracts, idebenone, resveratrol) to neutralize free radicals, and strand-coating silicones, proteins, and polymers, which provide a physical barrier, walling off hair from pollutants, says Hammer.

THE CLAIM: Healing hydration

WHAT IT MEANS FOR HAIR: With a rich blood supply and an abundance of oil glands, the scalp is an extension of our skin, says dermatologist Francesca Fusco . It shares the same lipids and humectants, and is equally prone to dryness and irritation. Hair suffers from dehydration, too, particularly when its cuticle is eroded (by water, heat, and chemicals).

WHAT WORKS: Hyaluronic acid, a water-binding humectant, and ceramides, moisture-retaining lipids, are both found naturally in the skin (and in countless creams and serums). Since they improve the functioning of skin cells, making them more resilient and efficient, both can help keep the scalp in peak condition. When applied to hair (again, leave-on products work best), they coat strands to lock in moisture while also shielding from heat and styling damage, says Rogers, noting a 2002 study in which ceramides were shown to bind to African hair, helping to reduce breakage. Coconut oil and panthenol (a B vitamin) also nourish the scalp, and unlike most other ingredients, can penetrate inside the hair shaft, hydrating from within to enhance pliability, and keeping the cuticle tight and intact.

Bottom Line: The secret to beautiful hair is a healthy scalp. When the scalp is out of whack meaning theres poor circulation, an oil imbalance, or a build-up of cells we see not only flakes and inflammation, but hair that looks and feels unhealthy, and may even shed before its time, says Fusco. Seek out proven actives that take aim at the scalp (many of which do hail from the skin realm): dandruff-fighting pyrithione zinc (in Doves new DermaCare Scalp collection); clays that absorb excess oil and calm irritation (like those in LOral Paris Extraordinary Clay Pre-Shampoo Mask ); exfoliating salicylic acid or willowbark extract, which keep cells shedding at a normal clip to prevent pile-ups; and the aforementioned hydrators to soothe and replenish dry, depleted follicles.

Check out the best new drugstore beauty products of 2017:

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Conservative Reps Urge Trump to Fire NIH Head – WMGT – 41 NBC News

By NEVAGiles23


41 NBC News
Conservative Reps Urge Trump to Fire NIH Head - WMGT
41 NBC News
Stem Cell Research.Experimenting with cells in petri dish by adding fluid from a pipette, used in therapeutic cloning, microbiology, genetic engineering an.

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Discovery of a key regulatory gene in cardiac valve formation – Medical Xpress

By NEVAGiles23

May 23, 2017

Researchers from the University of Basel in Switzerland have identified a key regulator gene for the formation of cardiac valves - a process crucial to normal embryonic heart development. These results are published in the journal Cell Reports today.

The heart is the first functional organ that develops in vertebrate embryos. In humans, it starts to beat four weeks into the pregnancy. Unfortunately, congenital heart disease is one of the most common developmental abnormalities and the leading cause of birth defect-related deaths. These heart defects often involve malformations of cardiac valves, which are required to regulate the pressure and flow of blood in the cardiac chambers.

Unexpected role for HAND2 transcription factor in cardiac valve formation

A research team led by Prof. Zeller and Dr. Zuniga from the University of Basel has identified the so-called HAND2 gene as a key regulator that triggers the formation of cardiac valves in mouse embryos, a process that is crucial for normal heart development. Previous research using mouse models lacking HAND2 had shown that this gene regulates outflow tract and right ventricle development.

The researchers thus set out to identify the set of genes that are controlled by HAND2 in developing mouse hearts. In doing so, they identified a previously unknown heart defect in mouse embryos lacking HAND2. The mutant hearts lack the cardiac cushions, which would normally develop into cardiac valves. Normally, the cells contributing to these cushions undergo complex cellular rearrangements as they detach from the lining of the heart wall and migrate into the cushions to "fill them up". As this mechanism is crucial for heart development, the researchers investigated how HAND2 controls this fundamental event during cardiac valve development.

HAND2 controlled gene network

In humans, defects in valve formation underlie different congenital heart malformations but the molecular mechanisms controlling heart valve development are not well understood. By studying mouse embryos, the research group has now identified the network of genes directly controlled by HAND2 that regulates cardiac valve formation.

The discovery of the HAND2 controlled gene network is of general relevance as mutations in HAND2 have recently been linked to heart valve malformations in human patients. «Not only does this discovery advance our molecular knowledge of cardiac valve development, but it may also help to provide genetic diagnosis for patients that suffer from congenital heart malformations," says first author Frderic Laurent of the Department of Biomedicine.

Engineering valves from stem cells

Heart valve replacements are among the most common cardiac surgeries performed and one of the future promises of biomedical research is to engineer replacement valves from stem cells. The discovery that HAND2 is a key regulator of the cellular and gene regulatory processes underlying heart valve formation is a potential milestone in this direction.

Explore further: Scientists get the upperhand in biological pathway that leads to heart formation

More information: Frdric Laurent, Ausra Girdziusaite, Julie Gamart, Iros Barozzi, Marco Osterwalder, Jennifer A. Akiyama, Joy Lincoln, Javier Lopez-Rios, Axel Visel, Aime Zuniga, and Rolf Zeller, HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development, Cell Reports 19 (2017) DOI: 10.1016/j.celrep.2017.05.004

Journal reference: Cell Reports

Provided by: University of Basel

Researchers at UT Southwestern Medical Center's Hamon Center for Regenerative Science and Medicine have identified a pathway essential to heart formation and, in the process, unveiled a mechanism that may explain how some ...

Researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have demonstrated the crucial role of the NOTCH signaling pathway in the development of a fundamental heart structure, the heart valves. ...

Heart valve defects are a common cause of death in newborns. Scientists at the University of Bonn and the caesar research center have discovered "Creld1" is a key gene for the development of heart valves in mice. The researchers ...

There are certain matters of the heart that should be left to the experts, and mitral valve disease is one of them. Dr. Joseph Lamelas, associate chief of cardiac surgery in the Michael E. DeBakey Department of Surgery at ...

A gene known to be important in cardiac development has been newly associated with congenital heart malformations that result in obstruction of the left ventricular outflow tract. These are the findings from a study conducted ...

May 5, 2016A cell-to-cell signaling network that serves as a developmental timer could provide a framework for better understanding the mechanisms underlying human heart valve disease, say University of Oregon scientists.

The first known identification of two genes responsible for hypoplastic left heart syndrome (HLHS), a severe congenital heart defect, has been reported by researchers at the University of Pittsburgh School of Medicine. The ...

Coronary artery disease (CAD) is a leading cause of death worldwide. Despite dozens of regions in the genome associated with CAD, most of the genetic components of heart disease are not fully understood, suggesting that more ...

A new gene behind a rare form of inherited childhood kidney disease has been identified by a global research team.

In the earliest stages of embryonic development, a protein known as TET1 may be the factor that tips the balance toward health or disease. The first evidence for this vital role of TET1 is presented in Nature Genetics by ...

Stop-and-go traffic is typically a source of frustration, an unneccesary hold-up on the path from point A to point B. But when it comes to the molecular machinery that copies our DNA into RNA, a stop right at the beginning ...

A new study of inherited genetic risk indicates that common genetic variations throughout the genome act in addition to rare, deleterious mutations in autism-associated genes to create risk for autism.

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Discovery of a key regulatory gene in cardiac valve formation - Medical Xpress

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Robot hearts: medicine’s new frontier – The Guardian

By raymumme

On a cold, bright January morning I walked south across Westminster Bridge to St Thomas Hospital, an institution with a proud tradition of innovation: I was there to observe a procedure generally regarded as the greatest advance in cardiac surgery since the turn of the millennium and one that can be performed without a surgeon.

The patient was a man in his 80s with aortic stenosis, a narrowed valve which was restricting outflow from the left ventricle into the aorta. His heart struggled to pump sufficient blood through the reduced aperture, and the muscle of the affected ventricle had thickened as the organ tried to compensate. If left unchecked, this would eventually lead to heart failure. For a healthier patient the solution would be simple: an operation to remove the diseased valve and replace it with a prosthesis. But the mans age and a long list of other medical conditions made open-heart surgery out of the question. Happily, for the last few years, another option has been available for such high-risk patients: transcatheter aortic valve implantation, known as TAVI for short.

This is a non-invasive procedure, and takes place not in an operating theatre but in the catheterisation laboratory, known as the cath lab. When I got there, wearing a heavy lead gown to protect me from X-rays, the patient was already lying on the table. He would remain awake throughout the procedure, receiving only a sedative and a powerful analgesic. I was shown the valve to be implanted, three leaflets fashioned from bovine pericardium (a tough membrane from around the heart of a cow), fixed inside a collapsible metal stent. After being soaked in saline it was crimped on to a balloon catheter and squeezed, from the size and shape of a lipstick, into a long, thin object like a pencil.

The consultant cardiologist, Bernard Prendergast, had already threaded a guidewire through an incision in the patients groin, entering the femoral artery and then the aorta, until the tip of the wire had arrived at the diseased aortic valve. The catheter, with its precious cargo, was then placed over the guidewire and pushed gently up the aorta. When it reached the upper part of the vessel we could track its progress on one of the large X-ray screens above the table. We watched intently as the metal stent described a slow curve around the aortic arch before coming to rest just above the heart.

There was a pause as the team checked everything was ready, while on the screen the silhouette of the furled valve oscillated gently as it was buffeted by pulses of high-pressure arterial blood. When Prendergast was satisfied that the catheter was precisely aligned with the aortic valve, he pressed a button to inflate the tiny balloon. As it expanded it forced the metal stent outwards and back to its normal diameter, and on the X-ray monitor it suddenly snapped into position, firmly anchored at the top of the ventricle. For a second or two the patient became agitated as the balloon obstructed the aorta and stopped the flow of blood to his brain; but as soon as it was deflated he became calm again.

Prendergast and his colleagues peered at the monitors to check the positioning of the device. In a conventional operation the diseased valve would be excised before the prosthesis was sewn in; during a TAVI procedure the old valve is left untouched and the new one simply placed inside it. This makes correct placement vital, since unless the device fits snugly there may be a leak around its edge. The X-ray picture showed that the new valve was securely anchored and moving in unison with the heart. Satisfied that everything had gone according to plan, Prendergast removed the catheter and announced the good news in a voice that was probably audible on the other side of the river. Just minutes after being given a new heart valve, the patient raised an arm from under the drapes and shook the cardiologists hand warmly. The entire procedure had taken less than an hour.

According to many experts, this is what the future will look like. Though available for little more than a decade, TAVI is already having a dramatic impact on surgical practice: in Germany the majority of aortic valve replacements, more than 10,000 a year, are now performed using the catheter rather than the scalpel.

In the UK, the figure is much lower, since the procedure is still significantly more expensive than surgery this is largely down to the cost of the valve itself, which can be as much as 20,000 for a single device. But as the manufacturers recoup their initial outlay on research and development, it is likely to become more affordable and its advantages are numerous. Early results suggest that it is every bit as effective as open-heart surgery, without many of surgerys undesirable aspects: the large chest incision, the heart-lung machine, the long period of post-operative recovery.

The essential idea of TAVI was first suggested more than half a century ago. In 1965, Hywel Davies, a cardiologist at Guys Hospital in London, was mulling over the problem of aortic regurgitation, in which blood flows backwards from the aorta into the heart. He was looking for a short-term therapy for patients too sick for immediate surgery something that would allow them to recover for a few days or weeks, until they were strong enough to undergo an operation. He hit upon the idea of a temporary device that could be inserted through a blood vessel, and designed a simple artificial valve resembling a conical parachute. Because it was made from fabric, it could be collapsed and mounted on to a catheter. It was inserted with the top of the parachute uppermost, so that any backwards flow would be caught by its inside surface like air hitting the underside of a real parachute canopy. As the fabric filled with blood it would balloon outwards, sealing the vessel and stopping most of the anomalous blood flow.

This was a truly imaginative suggestion, made at a time when catheter therapies had barely been conceived of, let alone tested. But, in tests on dogs, Davies found that his prototype tended to provoke blood clots and he was never able to use it on a patient.

Another two decades passed before anybody considered anything similar. That moment came in 1988, when a trainee cardiologist from Denmark, Henning Rud Andersen, was at a conference in Arizona, attending a lecture about coronary artery stenting. It was the first he had heard of the technique, which at the time had been used in only a few dozen patients, and as he sat in the auditorium he had a thought, which at first he dismissed as ridiculous: why not make a bigger stent, put a valve in the middle of it, and implant it into the heart via a catheter? On reflection, he realised that this was not such an absurd idea, and when he returned home to Denmark he visited a local butcher to buy a supply of pig hearts. Working in a pokey room in the basement of his hospital with basic tools obtained from a local DIY warehouse, Andersen constructed his first experimental prototypes. He began by cutting out the aortic valves from the pig hearts, mounted each inside a home-made metal lattice then compressed the whole contraption around a balloon.

Within a few months Andersen was ready to test the device in animals, and on 1 May 1989 he implanted the first in a pig. It thrived with its prosthesis, and Andersen assumed that his colleagues would be excited by his works obvious clinical potential. But nobody was prepared to take the concept seriously folding up a valve and then unfurling it inside the heart seemed wilfully eccentric and it took him several years to find a journal willing to publish his research.

When his paper was finally published in 1992, none of the major biotechnology firms showed any interest in developing the device. Andersens crazy idea worked, but still it sank without trace.

Andersen sold his patent and moved on to other things. But at the turn of the century there was a sudden explosion of interest in the idea of valve implantation via catheter. In 2000, a heart specialist in London, Philipp Bonhoeffer, replaced the diseased pulmonary valve of a 12-year-old boy, using a valve taken from a cows jugular vein, which had been mounted in a stent and put in position using a balloon catheter.

In France, another cardiologist was already working on doing the same for the aortic valve. Alain Cribier had been developing novel catheter therapies for years; it was his company that bought Andersens patent in 1995, and Cribier had persisted with the idea even after one potential investor told him that TAVI was the most stupid project ever heard of.

Eventually, Cribier managed to raise the necessary funds for development and long-term testing, and by 2000 had a working prototype. Rather than use an entire valve cut from a dead heart, as Andersen had, Cribier built one from bovine pericardium, mounted in a collapsible stainless-steel stent. Prototypes were implanted in sheep to test their durability: after two-and-a-half years, during which they opened and closed more than 100m times, the valves still worked perfectly.

Cribier was ready to test the device in humans, but his first patient could not be eligible for conventional surgical valve replacement, which is safe and highly effective: to test an unproven new procedure on such a patient would be to expose them to unnecessary risk.

In early 2002, he was introduced to a 57-year-old man who was, in surgical terms, a hopeless case. He had catastrophic aortic stenosis which had so weakened his heart that with each stroke it could pump less than a quarter of the normal volume of blood; in addition, the blood vessels of his extremities were ravaged by atherosclerosis, and he had chronic pancreatitis and lung cancer. Several surgeons had declined to operate on him, and his referral to Cribiers clinic in Rouen was a final roll of the dice. An initial attempt to open the stenotic valve using a simple balloon catheter failed, and a week after this treatment Cribier recorded in his notes that his patient was near death, with his heart barely functioning. The mans family agreed that an experimental treatment was preferable to none at all, and on 16 April he became the first person to receive a new aortic valve without open-heart surgery.

Over the next couple of days the patients condition improved dramatically: he was able to get out of bed, and the signs of heart failure began to retreat. But shortly afterwards complications arose, most seriously a deterioration in the condition of the blood vessels in his right leg, which had to be amputated 10 weeks later. Infection set in, and four months after the operation, he died.

He had not lived long nobody expected him to but the episode had proved the feasibility of the approach, with clear short-term benefit to the patient. When Cribier presented a video of the operation to colleagues they sat in stupefied silence, realising that they were watching something that would change the nature of heart surgery.

When surgeons and cardiologists overcame their initial scepticism about TAVI they quickly realised that it opened up a vista of exciting new surgical possibilities. As well as replacing diseased valves it is now also possible to repair them, using clever imitations of the techniques used by surgeons. The technology is still in its infancy, but many experts believe that this will eventually become the default option for valvular disease, making surgery increasingly rare.

While TAVI is impressive, there is one even more spectacular example of the capabilities of the catheter. Paediatric cardiologists at a few specialist centres have recently started using it to break the last taboo of heart surgery operating on an unborn child. Nowhere is the progress of cardiac surgery more stunning than in the field of congenital heart disease. Malformations of the heart are the most common form of birth defect, with as many as 5% of all babies born with some sort of cardiac anomaly though most of these will cause no serious, lasting problems. The heart is especially prone to abnormal development in the womb, with a myriad of possible ways in which its structures can be distorted or transposed. Over several decades, specialists have managed to find ways of taming most; but one that remains a significant challenge to even the best surgeon is hypoplastic left heart syndrome (HLHS), in which the entire left side of the heart fails to develop properly. The ventricle and aorta are much smaller than they should be, and the mitral valve is either absent or undersized. Until the early 1980s this was a defect that killed babies within days of birth, but a sequence of complex palliative operations now makes it possible for many to live into adulthood.

Because their left ventricle is incapable of propelling oxygenated blood into the body, babies born with HLHS can only survive if there is some communication between the pulmonary and systemic circulations, allowing the right ventricle to pump blood both to the lungs and to the rest of the body. Some children with HLHS also have an atrial septal defect (ASD), a persistent hole in the tissue between the atria of the heart which improves their chances of survival by increasing the amount of oxygenated blood that reaches the sole functioning pumping chamber. When surgeons realised that this defect conferred a survival benefit in babies with HLHS, they began to create one artificially in those with an intact septum, usually a few hours after birth. But it was already too late: elevated blood pressure was causing permanent damage to the delicate vessels of the lungs while these babies still in the womb.

The logical albeit risky response was to intervene even earlier. In 2000, a team at Boston Childrens Hospital adopted a new procedure to create an ASD during the final trimester of pregnancy: they would deliberately create one heart defect in order to treat another. A needle was passed through the wall of the uterus and into the babys heart, and a balloon catheter used to create a hole between the left and right atria. This reduced the pressures in the pulmonary circulation and hence limited the damage to the lungs; but the tissues of a growing foetus have a remarkable ability to repair themselves, and the artificially created hole would often heal within a few weeks. Cardiologists needed to find a way of keeping it open until birth, when surgeons would be able to perform a more comprehensive repair.

In September 2005 a couple from Virginia, Angela and Jay VanDerwerken, visited their local hospital for a routine antenatal scan. They were devastated to learn that their unborn child had HLHS, and the prognosis was poor. The ultrasound pictures revealed an intact septum, making it likely that even before birth her lungs would be damaged beyond repair. They were told that they could either terminate the pregnancy or accept that their daughter would have to undergo open-heart surgery within hours of her birth, with only a 20% chance that she would survive.

Devastated, the VanDerwerkens returned home, where Angela researched the condition online. Although few hospitals offered any treatment for HLHS, she found several references to the Boston foetal cardiac intervention programme, the team of doctors that had pioneered the use of the balloon catheter during pregnancy.

They arranged an appointment with Wayne Tworetzky, the director of foetal cardiology at Boston Childrens Hospital, who performed a scan and confirmed that their unborn childs condition was treatable. A greying, softly spoken South African, Tworetzky explained that his team had recently developed a new procedure, but that it had never been tested on a patient. It would mean not just making a hole in the septum, but also inserting a device to prevent it from closing. The VanDerwerkens had few qualms about accepting the opportunity: the alternatives gave their daughter a negligible chance of life.

The procedure took place at Brigham and Womens Hospital in Boston on 7 November 2005, 30 weeks into the pregnancy, in a crowded operating theatre. Sixteen doctors, with a range of specialisms, took part: cardiologists, surgeons, and four anaesthetists two to look after the mother, two for her unborn child. Mother and child needed to be completely immobilised during a delicate procedure lasting several hours, so both were given a general anaesthetic. The team watched on the screen of an ultrasound scanner as a thin needle was guided through the wall of the uterus, then the foetuss chest and finally into her heart an object the size of a grape.

A guidewire was placed in the cardiac chambers, then a tiny balloon catheter was inserted and used to create an opening in the atrial septum. This had all been done before; but now the cardiologists added a refinement. The balloon was withdrawn, then returned to the heart, this time loaded with a 2.5 millimetre stent that was set in the opening between the left and right atria. There was a charged silence as the balloon was inflated to expand the stent; then, as the team saw on the monitor that blood was flowing freely through the aperture, the room erupted in cheers.

Grace VanDerwerken was born in early January after a normal labour, and shortly afterwards underwent open-heart surgery. After a fortnight she was allowed home, her healthy pink complexion proving that the interventions had succeeded in producing a functional circulation.

But just when she seemed to be out of danger, Grace died suddenly at the age of 36 days not as a consequence of the surgery, but from a rare arrhythmia, a complication of HLHS that occurs in just 5%. This was the cruellest luck, when she had seemingly overcome the grim odds against her. Her death was a tragic loss, but her parents courage had brought about a new era in foetal surgery.

Much of the most exciting contemporary research focuses on the greatest, most fundamental cardiac question of all: what can the surgeon do about the failing heart? Half a century after Christiaan Barnard performed the first human heart transplant, transplantation remains the gold standard of care for patients in irreversible heart failure once drugs have ceased to be effective. It is an excellent operation, too, with patients surviving an average of 15 years. But it will never be the panacea that many predicted, because there just arent enough donor hearts to go round.

With too few organs available, surgeons have had to think laterally. As a result, a new generation of artificial hearts is now in development. Several companies are now working on artificial hearts with tiny rotary electrical motors. In addition to being much smaller and more efficient than pneumatic pumps, these devices are far more durable, since the rotors that impel the blood are suspended magnetically and are not subject to the wear and tear caused by friction. Animal trials have shown promising results, but, as yet, none of these have been implanted in a patient.

Another type of total artificial heart, as such devices are known, has, however, recently been tested in humans. Alain Carpentier, an eminent French surgeon still active in his ninth decade, has collaborated with engineers from the French aeronautical firm Airbus to design a pulsatile, hydraulically powered device whose unique feature is the use of bioprosthetic materials both organic and synthetic matter. Unlike earlier artificial hearts, its design mimics the shape of the natural organ; the internal surfaces are lined with preserved bovine pericardial tissue, a biological surface far kinder to the red blood cells than the polymers previously used. Carpentiers artificial heart was first implanted in December 2013. Although the first four patients have since died two following component failures the results were encouraging, and a larger clinical trial is now under way.

One drawback to the artificial heart still leads many surgeons to dismiss the entire concept out of hand: the price tag. These high-precision devices cost in excess of 100,000 each, and no healthcare service in the world, publicly or privately funded, could afford to provide them to everybody in need of one. And there is one still more tantalising notion: that we will one day be able to engineer spare parts for the heart, or even an entire organ, in the laboratory.

In the 1980s, surgeons began to fabricate artificial skin for burns patients, seeding sheets of collagen or polymer with specialised cells in the hope that they would multiply and form a skin-like protective layer. But researchers had loftier ambitions, and a new field tissue engineering began to emerge.

High on the list of priorities for tissue engineers was the creation of artificial blood vessels, which would have applications across the full range of surgical specialisms. In 1999 surgeons in Tokyo performed a remarkable operation in which they gave a four-year-old girl a new artery grown from cells taken from elsewhere in her body. She had been born with a rare congenital defect which had completely obliterated the right branch of her pulmonary artery, the vessel conveying blood to the right lung. A short section of vein was excised from her leg, and cells from its inside wall were removed in the laboratory. They were then left to multiply in a bioreactor, a vessel that bathed them in a warm nutrient broth, simulating conditions inside the body.

After eight weeks, they had increased in number to more than 12m, and were used to seed the inside of a polymer tube which functioned as a scaffold for the new vessel. The tissue was allowed to continue growing for 10 days, and then the graft was transplanted. Two months later the polymer scaffold around the tissue, designed to break down inside the body, had completely dissolved, leaving only new tissue that would it was hoped grow with the patient.

At the turn of the millennium, a new world of possibility opened up when researchers gained a powerful new tool: stem cell technology. Stem cells are not specialised to one function but have the potential to develop into many different tissue types. One type of stem cell is found in growing embryos, and another in parts of the adult body, including the bone marrow (where they generate the cells of the blood and immune system) and skin. In 1998 James Thomson, a biologist at the University of Wisconsin, succeeded in isolating stem cells from human embryos and growing them in the laboratory.

But an arguably even more important breakthrough came nine years later, when Shinya Yamanaka, a researcher at Kyoto University, showed that it was possible to genetically reprogram skin cells and convert them into stem cells. The implications were enormous. In theory, it would now be possible to harvest mature, specialised cells from a patient, reprogram them as stem cells, then choose which type of tissue they would become.

Sanjay Sinha, a cardiologist at the University of Cambridge, is attempting to grow a patch of artificial myocardium (heart muscle tissue) in the laboratory for later implantation in the operating theatre. His technique starts with undifferentiated stem cells, which are then encouraged to develop into several types of specialised cell. These are then seeded on to a scaffold made from collagen, a tough protein found in connective tissue. The presence of several different cell types means that when they have had time to proliferate, the new tissue will develop its own blood supply.

Clinical trials are still some years away, but Sinha hopes that one day it will be possible to repair a damaged heart by sewing one of these patches over areas of muscle scarred by a heart attack.

Using advanced tissue-engineering techniques, researchers have already succeeded in creating replacement valves from the patients own tissue. This can be done by harvesting cells from elsewhere in the body (usually the blood vessels) and breeding them in a bioreactor, before seeding them on to a biodegradable polymer scaffold designed in the shape of a valve. Once the cells are in place they are allowed to proliferate before implantation, after which the scaffold melts away, leaving nothing but new tissue. The one major disadvantage of this approach is that each valve has to be tailor-made for a specific patient, a process that takes weeks. In the last couple of years, a group in Berlin has refined the process by tissue-engineering a valve and then stripping it of cellular material, leaving behind just the extracellular matrix the structure that holds the cells in position.

The end result is therefore not quite a valve, but a skeleton on which the body lays down new tissue. Valves manufactured in this way can be implanted, via catheter, in anybody; moreover, unlike conventional prosthetic devices, if the recipient is a child the new valve should grow with them.

If it is possible to tissue-engineer a valve, then why not an entire heart? For many researchers this has come to be the ultimate prize, and the idea is not necessarily as fanciful as it first appears.

In 2008, a team led by Doris Taylor, a scientist at the University of Minnesota, announced the creation of the worlds first bioartificial heart composed of both living and manufactured parts. They began by pumping detergents through hearts excised from rats. This removed all the cellular tissue from them, leaving a ghostly heart-shaped skeleton of extracellular matrix and connective fibre, which was used as a scaffold onto which cardiac or blood-vessel cells were seeded. The organ was then cultured in a bioreactor to encourage cell multiplication, with blood constantly perfused through the coronary arteries. After four days, it was possible to see the new tissue contracting, and after a week the heart was even capable of pumping blood though only 2% of its normal volume.

This was a brilliant achievement, but scaling the procedure up to generate a human-sized heart is made far more difficult by the much greater number of cells required. Surgeons in Heidelberg have since applied similar techniques to generate a human-sized cardiac scaffold covered in living tissue. The original heart came from a pig, and after it had been decellularised it was populated with human vascular cells and cardiac cells harvested from a newborn rat. After 10 days the walls of the organ had become lined with new myocardium which even showed signs of electrical activity. As a proof of concept, the experiment was a success, though after three weeks of culture the organ could neither contract nor pump blood.

Growing tissues and organs in a bioreactor is a laborious business, but recent improvements in 3D printing offer the tantalising possibility of manufacturing a new heart rapidly and to order. 3D printers work by breaking down a three-dimensional object into a series of thin, two-dimensional slices, which are laid down one on top of another. The technology has already been employed to manufacture complex engineering components out of metal or plastic, but it is now being used to generate tissues in the laboratory. To make an aortic valve, researchers at Cornell University took a pigs valve and X-rayed it in a high-resolution CT scanner. This gave them a precise map of its internal structure which could be used as a template. Using the data from the scan, the printer extruded thin jets of a hydrogel, a water-absorbent polymer that mimics natural tissue, gradually building up a duplicate of the pig valve layer by layer. This scaffold could then be seeded with living cells and incubated in the normal way.

Pushing the technology further, Adam Feinberg, a materials scientist at Carnegie Mellon University in Pittsburgh, recently succeeded in fabricating the first anatomically accurate 3D-printed heart. This facsimile was made of hydrogel and contained no tissue, but it did show a remarkable fidelity to the original organ. Since then, Feinberg has used natural proteins such as fibrin and collagen to 3D-print hearts. For many researchers in this field, a fully tissue-engineered heart is the ultimate prize.

We are left with several competing visions of the future. Within a few decades it is possible that we will be breeding transgenic pigs in vast sterile farms and harvesting their hearts to implant in sick patients. Or that new organs will be 3D-printed to order in factories, before being dispatched in drones to wherever they are needed. Or maybe an unexpected breakthrough in energy technology will make it possible to develop a fully implantable, permanent mechanical heart.

Whatever the future holds, it is worth reflecting on how much has been achieved in so little time. Speaking in 1902, six years after Ludwig Rehn became the first person to perform cardiac surgery, Harry Sherman remarked that the road to the heart is only two or three centimetres in a direct line, but it has taken surgery nearly 2,400 years to travel it. Overcoming centuries of cultural and medical prejudice required a degree of courage and vision still difficult to appreciate today. Even after that first step had been taken, another 50 years elapsed before surgeons began to make any real progress. Then, in a dizzying period of three decades, they learned how to open the heart, repair and even replace it. In most fields, an era of such fundamental discoveries happens only once if at all and it is unlikely that cardiac surgeons will ever again captivate the world as Christiaan Barnard and his colleagues did in 1967. But the history of heart surgery is littered with breakthroughs nobody saw coming, and as long as there are surgeons of talent and imagination, and a determination to do better for their patients, there is every chance that they will continue to surprise us.

Main photograph: Getty Images

This is an adapted extract from The Matter of the Heart by Thomas Morris, published by the Bodley Head

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Robot hearts: medicine's new frontier - The Guardian

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Miltenyi Biotec Showcases the Generation of Purified Human iPSC Derived Cardiomyocytes – PR Web (press release)

By LizaAVILA

Todd J. Herron, BS, PhD Director of the Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory and Assistant Research Professor at the University of Michigan Center for Arrhythmia

Yorba Linda, Ca (PRWEB) May 23, 2017

Pluripotent stem cells (PSCs) offer an unlimited source of human cardiovascular cells for research and the development of cardiac regeneration therapies. The development of highly efficient cardiac-directed differentiation methods makes it possible to generate large numbers of cardiomyocytes (hPSC-CMs). Due to varying differentiation efficiencies, further enrichment of CM populations for downstream applications is essential.

Recently, a CM-specific cell surface marker called SIRPa (signal-regulatory protein alpha, also termed CD172a) was reported to be a useful tool for flow sorting of human stem cellderived CMs. However, our expression analysis revealed that SIRPa only labels a subpopulation of CMs indicated by cardiac Troponin T (cTnT) expression. Moreover, SIRPa is also expressed on a sub population of non-CMs, hence making SIRa an inadequate marker to enrich PSC-derived CMs.

In this webinar, sponsored by the team at Miltenyi Biotec, participants will have a chance to review human induced pluripotent stem cell derivation, cardiac directed differentiation to human pluripotent stem cell cardiomyocytes (hPSC-CMs), enrichment of hPSC-CMs and subsequent formation of 2D monolayers of electrically connected cells. They will also learn of the generation of purified human induced pluripotent stem cell derived cardiomyocyte.

The speaker for this event will be Dr. Todd J. Herron, director of the Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory and Assistant Research Professor at the University of Michigan Center for Arrhythmia Research.

Herron currently serves as the director of the Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, as well as holding a position on the faculty in the University of Michigan Medical School and has appointments in the Department of Internal Medicine and Molecular & Integrative Physiology as Associate Research Scientist. His research is focused on the complex interplay between cardiac electrical excitation and contractile force generation-a process known classically as excitation-contraction coupling.

LabRoots will host the event June 7, 2017, beginning at 9 a.m. PDT, 12 p.m. EDT. To read more about this event, learn about the continuing education credits offered, or to register for free, click here.

ABOUT MILTENYI BIOTEC Miltenyi Biotec is a global provider of products and services that advance biomedical research and cellular therapy. The companys innovative tools support research at every level, from basic research to translational research to clinical application. This integrated portfolio enables scientists and clinicians to obtain, analyze, and utilize the cell. Miltenyi Biotecs technologies cover techniques of sample preparation, cell isolation, cell sorting, flow cytometry, cell culture, molecular analysis, and preclinical imaging. Their more than 25 years of expertise spans research areas including immunology, stem cell biology, neuroscience, and cancer, and clinical research areas like hematology, graft engineering, and apheresis. In their commitment to the scientific community, Miltenyi Biotec also offers comprehensive scientific support, consultation, and expert training. Today, Miltenyi Biotec has more than 1,500 employees in 25 countries all dedicated to helping researchers and clinicians around the world make a greater impact on science and health.

ABOUT LABROOTS LabRoots is the leading scientific social networking website, which provides daily scientific trending news and science-themed apparel, as well as produces educational virtual events and webinars, on the latest discoveries and advancements in science. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the worlds largest series of virtual events within the Life Sciences and Clinical Diagnostics community.

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Miltenyi Biotec Showcases the Generation of Purified Human iPSC Derived Cardiomyocytes - PR Web (press release)

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AHA awards $2 million to cardiac research at top universities – Cardiovascular Business

By daniellenierenberg

The American Heart Association (AHA) announced May 19 that it will donate two $1 million research grants to support research on medications and high blood pressure.

The money will be awarded over five years to Stanford University and the University of Pennsylvania, according to a statement from the AHA.

[These] competitive research programs are pushing the boundaries of their respective disciplines by undertaking high-risk projects whose outcomes could revolutionize the treatment for new classes of blood pressure medications and our approaches for clinical trials in the era of precision medicine, said Ivor Benjamin, MD, who chairs the AHAs research committee.

Joseph Wu, MD, the director of theStanford Cardiovascular Institute at Stanford University School of Medicine, is leading the research on medication. He plans to use information from stem cells to speed up the slow and expensive process of introducing a new drug to the market.

Our project has tremendous potential significance for testing new drugs very efficiently compared to the traditional drug screening that the pharmaceutical industry has to go througha process that has stagnated and become almost too costly to help patients, Wu said.

The second research project, spearheaded by Garret FitzGerald, MD, a professor of medicine and systems pharmacology and translational therapeutics at the University of Pennsylvanias Perelman School of Medicine, aims to improve blood pressure control over a 24-hour period.

Given the increasing prevalence of high blood pressure in our aging population and in the developing world generally, this program promises to have a considerable impact on global health, FitzGerald said.

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Stem cell treatments ready to replace medicine in 10 years: Expert – Jakarta Post

By JoanneRUSSELL25

Currently, there are only 11 hospitals that are authorized to give stem cell treatments in Indonesia. (Shutterstock/File)

Developments in science and technology have enabled humankind to achieve the unthinkable, including advancements in healthcare. In the next 10 years, patients may not even need medicine to cure certain illnesses as reported by kompas.com.

Principal investigator of Stem Cell and Cancer Institute, Dr. Yuyus Kusnadi, said health scientists are developing stem cell treatments. Stem cells are cells with the ability to renew or regenerate any kind of cells.

Degenerative conditions such as kidney failure and the weakening of heart muscles in the future may be cured by injecting stem cells into the patients body.

Stem cells can be obtained from umbilical cord blood that is kept in a stem cell bank, back bone marrow and fat. However, fat and bone marrow will decline in quality as a person grows older. Stem cells stored in a stem cell bank can be used for future treatments if needed.

Read also: Scientists take first steps to growing human organs in pigs

Health treatments using stem cells exist today although they are not yet developed due to limitations in funding and technology. Yuyus said in Indonesia, those who are allowed stem cell treatment are those who have no option.

For now, stem cell treatment require a doctors approval. Its still subjective, he said.

For those with recommendations for stem cell treatment, the stem cell is obtained from blood or fat. Manipulation in the laboratory is needed to strengthen the stem cell.

Although stem cell treatments are not yet popular these days, Yuyus is optimistic, Lets wait five to ten more years. The current use of medicine only stops symptoms and does not fix the sickness, he said.

Stem cell treatments will not be cheap either, as it will cost patients up to hundreds of millions of rupiah.

Currently, there are only 11 hospitals that are authorized to give stem cell treatments in Indonesia. The hospitals right to provide stem cell treatments is regulated in the Health Ministers Regulation no. 32, 2014 on the Incorporation of Medical Research Service and Education of Tissue and Stem Cell Centers.

Hospitals authorized to provide stem cell treatments in Indonesia include Rumah Sakit Cipto Mangun Kusumo, RS. Sutomo, RS M. Djamil, RS. Persahabatan, RS. Fatmawati, RS. Dharmais, RS. Harapan Kita, RS. Hasan Sadikin, RS. Kariadi, RS. Sardjito and RS. Sanglah. (asw)

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What are Stem Cells? – Health News – Medical News Today

By JoanneRUSSELL25

knowledge center home stem cell research all about stem cells what are stem cells?

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources:

Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.

Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.

However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the "inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher - a process known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem cells.

Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most potent since they must become every type of cell in the body. The full classification includes:

Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta.

A video on how stem cells work and develop.

Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the laboratory to check for these properties.

One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and immune cells, it demonstrates its potency.

Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated or they may examine chromosomes.

To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of differentiated cells).

Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body, for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore, stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells powerful enough to regenerate damaged tissue under the right conditions.

Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.

A team of researchers from Massachusetts General Hospital reported in PNAS Early Edition (July 2013 issue) that they were able to create blood vessels in laboratory mice using human stem cells.

The scientists extracted vascular precursor cells derived from human-induced pluripotent stem cells from one group of adults with type 1 diabetes as well as from another group of healthy adults. They were then implanted onto the surface of the brains of the mice.

Within two weeks of implanting the stem cells, networks of blood-perfused vessels had been formed - they lasted for 280 days. These new blood vessels were as good as the adjacent natural ones.

The authors explained that using stem cells to repair or regenerate blood vessels could eventually help treat human patients with cardiovascular and vascular diseases.

Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson's and Alzheimer's by replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving. Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are promising.

Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease, repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to replace the insulin-producing cells that have been lost or destroyed by the patient's own immune system. The only current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for transplant.

Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types, such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make these powerful cells more easily obtainable and to decrease the chances of a body's rejecting therapy.

Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug's effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on human volunteers.

The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a fully-developed human.

The core of this debate - similar to debates about abortion, for example - centers on the question, "When does life begin?" Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark the beginning of life - after the development of certain organs or after a certain time period.

People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop. This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people, however, object to the creation of an organism that is "part human".

The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However, the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that were created after August 2001.

Medical News Today is a leading resource for the latest headlines on stem cell research. So, check out our stem cell research news section. You can also sign up to our weekly or daily newsletters to ensure that you stay up-to-date with the latest news.

This stem cells information section was written by Peter Crosta for Medical News Today in September 2008 and was last updated on 19 July 2013. The contents may not be re-produced in any way without the permission of Medical News Today.

Disclaimer: This informational section on Medical News Today is regularly reviewed and updated, and provided for general information purposes only. The materials contained within this guide do not constitute medical or pharmaceutical advice, which should be sought from qualified medical and pharmaceutical advisers.

Please note that although you may feel free to cite and quote this article, it may not be re-produced in full without the permission of Medical News Today. For further details, please view our full terms of use

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