Stem Cell Clinic

Texas gives green-light for experimental stem-cell therapies – BioEdge

By adminJune 24, 2017Stem Cell Treatment

The government of Texas will allow clinics across the state to market unapproved stem-cell therapies, in a move that has met with criticism from bioethicists.

Last week Governor Greg Abbott signed off on the new legislation that allows clinics to by-pass FDA approval for investigational stem cell treatments for patients with certain severe chronic diseases or terminal illnesses. Like right to try laws in other States, the Texas legislation will give desperate patients access to therapies that provide hope after traditional medical treatments have failed.

Currently, most patients wishing to have stem-cell therapy have to travel out of the country to receive it. The new law will allow people with severe chronic or terminal illness to be treated at a clinic that purports to isolate therapeutic stem cells from adult tissuesuch as a patients own fatif their doctor recommends it after considering all other options, and if its administered by a physician at a hospital or medical school with oversight from an institutional review board (IRB). It also requires that the same intervention already be tested on humans in a clinical trial.

The law sanctions a much broader set of therapies than federal rules, which already exempt certain stem cell interventions from FDAs lengthy approval process, provided the cells are only minimally manipulated and perform the same function they normally have in the body.

Bioethicists have expressed their concern at the move, which they say puts patients at risk of the effects of dangerous, untested therapies.

University of Minnesota bioethicist Leigh Turner said he was sceptical about whether the clinics would be adequately monitored, while NYU Langone Medical Center bioethicist Beth Roxland said it was insufficient to have the therapies tested in clinical trials while by-passing FDA approval. You could gain access to something [as long as its] being studied in a human somewhere on the planet, Roxland told Science, which in the stem cell area makes it really very scary.

Stem cells: the future of medicine – Medical Xpress

By adminJune 24, 2017Stell Cell Research

June 23, 2017

Imagine being able to take cells from your skin, transform them into other types of cells, such as lung, brain, heart or muscle cells, and use those to cure your ailments, from diabetes to heart disease or macular degeneration. To realise this, however, challenges still remain, Professor Janet Rossant, a pioneer in the field, says.

All across the world, scientists have begun clinical trials to try and do just that, by making use of the incredible power and versatility of stem cells, which are special cells that can make endless copies of themselves and transform into every other type of cell.

While human embryos contain embryonic stem cells, which help them to develop, the use of those cells has been controversial. The scientists are using induced pluripotent stem cells instead, which are other cells that have been reprogrammed to behave like stem cells.

"There are still significant challenges that we need to overcome, but in the long run we might even be able to create organs from stem cells taken from patients. That would enable rejection-free transplants," said Professor Janet Rossant, a pioneer in the field.

The mouse that changed everything

A speaker at the recent Commonwealth Science Conference 2017 held in Singapore and organised by Britain's Royal Society and Singapore's National Research Foundation, Prof Rossant gave an overview of stem cells' origins, history, uses and potential.

Now a senior scientist at The Hospital for Sick Children (also known as Sick Kids) in Toronto, Canada, after a decade as its chief of research, she was the first scientist to demonstrate the full power of stem cells in mice.

In the early 1990s, scientists believed that stem cells could only become certain types of cells and carry out limited functions. Based on her own research and that of others, however, Prof Rossant believed that they were capable of far more.

Working with other scientists, she created an entire mouse out of stem cells in 1992, upending the conventional wisdom. "We went on to create many baby mice that were completely normal, and completely derived from stem cells grown in a petri dish," she said.

"That was an amazing experiment, and it was instrumental in making people believe that human embryonic stem cells could have the full potential to make every cell type in the body," she added.

When scientists learned how to remove stem cells from human embryos in 1998, however, controversy ensued. Many lobbied against the cells' use in medical research and treatment due to the moral implications of destroying even unwanted embryos to gain the cells.

In Canada, Prof Rossant chaired the working group of the Canadian Institutes of Health Research on Stem Cell Research, establishing guidelines for the field. These guidelines helped to keep the field alive in Canada, and were influential well beyond the country's borders.

In 2006, Japanese researchers succeeded in taking skin cells from adult mice and reprogramming them to behave like embryonic stem cells. These revolutionary, induced pluripotent stem (IPS) cells allowed scientists to sidestep the ongoing controversy.

The challenges in the way

While stem cells have been used for medical treatment in some cases bone marrow transplants, for example, are a form of stem cell therapy there are several challenges that need to be overcome before they can be used more widely to treat diseases and injuries.

"We need to get better at turning stem cells into the fully mature cells that you need for therapy. That's going to take more work. Another issue is that of scale-up. If you're going to treat a patient, you need to be able to grow millions of cells," said Prof Rossant.

She added: "Safety is another concern. One of the most exciting things about pluripotent stem cells is that they can divide indefinitely in the culture dish. But that's also one of the most scary things about them, because that's also how cancer works.

"Furthermore, because we need to genetically manipulate cells to get IPS cells, it's very hard to know whether we've got completely normal cells at the end of the day. These are all issues that need to be resolved."

She noted that some scientists are working on making "failsafe" IPS cells, which have a built-in self-destruct option if they become dangerous. "Bringing stem cells into regenerative medicine is going to require interdisciplinary, international collaboration," she said.

In the meantime, stem cells have been a boon to medical research, as scientists can use them to create an endless supply of different cells to study diseases and injuries, and test drugs. "That's the biggest use of IPS cells right now," Prof Rossant said.

Sick kids and how to help them

At SickKids, which is Canada's largest paediatric research hospital, she has been using stem cells to study cystic fibrosis, a frequently fatal genetic disorder that causes mucus to build up and clog some organs such as the lungs. It affects primarily children and young adults.

SickKids discovered the CFTR gene that, when mutated, causes the disease. It was also the first to produce mature lung cells, from stem cells, that can be used to study the disease and test drugs against it.

Even better, Prof Rossant and her team were able to turn skin cells from cystic fibrosis patients into IPS cells and then into lung cells with the genetic mutation specific to each of them. This is critical to personalising treatment for each patient.

"Drugs for cystic fibrosis are extraordinarily expensive, and patients can have the same mutation and yet respond differently to the same drug," Prof Rossant explained. "With our work, we can make sure that each patient gets the right drug at the right time."

In 1998, Prof Rossant also discovered a new type of stem cell in mice, now called the trophoblast stem cell. These surround an embryo and attach it to the uterine wall, eventually becoming the placenta. She is using such cells to study placenta defects and pregnancy problems.

By using IPS cells to create heart cells and other cells, pharmaceutical companies can also test their new drugs' effectiveness and uncover potential side effects, as well as develop personalised medicines.

"There are still huge amounts of opportunities in pluripotent stem cells," said Prof Rossant, who has won numerous awards for her research, including the Companion of the Order of Canada and the 2016 Friesen International Prize in Health Research.

She is also president and scientific director of the Toronto-based Gairdner Foundation, which recognises outstanding biomedical research worldwide, and a professor at the University of Toronto's molecular genetics, obstetrics and gynaecology departments.

"Meetings like the Commonwealth Science Conference are a fantastic opportunity for scientists to come together, learn about each other's work and establish new relationships, which will help to push science forward, including in stem cell research," she said.

She noted: "The world of science is becoming increasingly interdisciplinary, so this kind of meeting of minds across nations, cultures and scientific fields is really the way of the future."

Explore further: Cardiac stem cells from heart disease patients may be harmful

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Clear View on Stem Cell Development – Technology Networks

By adminJune 24, 2017Stell Cell Research

Today, tracking the development of individual cells and spotting the associated factors under the microscope is nothing unusual. However, impairments like shadows or changes in the background complicate the interpretation of data. Now, researchers at the Technical University of Munich (TUM) and the Helmholtz Zentrum Mnchen have developed a software that corrects images to make hidden development steps visible.

When stem cells develop into specialized cells, this happens in multiple steps. But which regulatory proteins are active during the decisive branching on the development path? Using so-called time-lapse microscopy, researchers can observe individual cells at very high time resolutions and, using fluorescent labelling, they can recognize precisely which of these proteins appear when in the cell.

Once a stem cell has been identified, it can be closely observed over several days using cell-tracking software. Yet, this surveillance work often turns out to be difficult. The imaging data is frequently marred by irregular brightness and faded backgrounds in the time-lapse, explains Dr. Carsten Marr, heading the workgroup Quantitative Single Cell Dynamics at the Institute of Computational Biology (ICB) of the Helmholtz Zentrum Mnchen. This makes it difficult or impossible to detect proteins that are decisive when a cell opts for a specific development direction, so-called transcription factors.

Algorithms that filter out these kinds of artefacts exist, but they require either specifically prepared reference images, many images per dataset or complex manual adjustments. Furthermore, none of the existing methods correct alterations in the background over time, which hamper the quantification of individual cells.

Algorithm eliminates background changes Now, Dr. Tingying Peng, member of Dr. Carsten Marrs group at the Helmholtz Zentrum Mnchen and Professor Nassir Navab, head of the Chair for Computer Aided Medical Procedures and Augmented Reality at TU Munich, present an algorithm that corrects these artefacts using only a few images per dataset.

The software is called BaSiC and is freely available. It is compatible with many image formats commonly used in bioimaging, including mosaics pieced together from numerous smaller images and used, for example, to render large tissue regions. Contrary to other programs, however, explains Dr. Peng, BaSiC can correct changes in the background of time-lapse videos. This makes it a valuable tool for stem cell researchers who want to detect the appearance of specific transcription factors early on. Bringing significant details to light How well the new image correction program improves the analysis of individual stem cell development steps the scientists demonstrated with time-lapse videos of blood stem cells. They recorded the videos to observe cells over a six-day time span. At a certain point during this observation period undifferentiated precursor cells choose between two possible tacks of development that lead to the formation of different mature blood cells.

In images corrected using BaSiC, the researchers could identify a substantial increase in the intensity of a specific transcription factor in one of the two cell lines, while the amount of his protein in the other cell line remained unchanged. Without the image correction, the difference was not ascertainable.

Using BaSiC, we were able to make important decision factors visible that would otherwise have been drowned out by noise, says Nassir Navab. The long-term goal of this research is to facilitate influencing the development of stem cells in a targeted manner, for example to cultivate new heart muscle cells for heat-attack patients. The novel possibilities for observation are bringing us a step closer to this goal.

The BaSiC image correction program resulted from a close collaboration between the Chair of Mathematical Modeling of Biological Systems and the Chair of Computer Aided Medical Procedures & Augmented Reality at the Technical University of Munich and the Institute of Computational Biology (ICB) of the Helmholtz Zentrum Mnchen. Also involved were the Department of Biochemistry and Biophysics at the University of California in San Francisco (USA), as well as the Department of Biosystems Science and Engineering (D-BSSSE) at ETH Zrich and the Chair of Computer Aided Medical Procedure at Johns Hopkins University in Baltimore (USA).

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

Reference:

Tingying Peng, Kurt Thorn, Timm Schroeder, Lichao Wang, Fabian J. Theis, Carsten Marr and Nassir Navab. BaSiC: A Tool for Background and Shading Correction of Optical Microscopy Images. Nature Communications 8, 14836 (2017) DOI: 10.1038/ncomms14836

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Powerful boost for bad skin days – Inquirer.net

By adminJune 22, 2017Stem Cell Clinic

These drips dont only improve your appearance.

Aivee (IV) Drips are safe, injectable treatments that restore the skins energy, vitality and glow fast because they go directly into the vein. The rains are a welcome respite, even as the wet season still feels hot as summer. But it also means we are susceptible to colds and bad skin days.

Oral medicine and green smoothies can only do so much to our bodies. What busy bees really need is a rapid, powerful boost in our systems that can get us looking and feeling great again in no time.

Its good to know the Aivee Clinic (my trusted skin superhero) is offering Aivee (IV) Dripssafe, injectable treatments that help restore energy, vitality and glow faster because they go directly into the vein. Administered in clinics, these drips dont only improve your appearance. Youll be surprised, like I was, by how varied the infusions are.

Revive Drip (Immune Boost) is a great pick-me-up after a long, stressful day at work. Infused with vitamin B complex, vitamin C, glutathione and other minerals, this antioxidant solution restores balance in the body and promotes skin hydration as it eliminates traces of fatigue fast. It isnt nicknamed the ultimate hangover cure for nothing.

Platinum flaunts a mix of vitamins, antioxidants, coenzyme Q10, minerals and other antiaging extracts best for those who seek a renewed glow reminiscent of their youth. This drip is a powerful antiwrinkle solution that helps boost energy and speed up skin recovery.

Brighter skin

For those who want brighter, more luminous skin without avoiding the sun, Glow (Frosty White) detoxifies with its blend of vitamin C and glutathione. The antioxidants in this mix also aid the immune system, taking this a notch above the usual whitening solution.

Athletes can also get a dose of drips fit for their lifestyle. PowerBoost is best for restoring physical performance with a mixture of magnesium, B-complex vitamins and glutathione.

ReShape is a great blend for weight-watchers who hope to stay in perfect shape with a drip infused with vitamins, slimming L-carnitine, and other potent fat-burners and antioxidants. Its an effective way to complement your exercise, burn fat and help keep the body healthy.

Finding light

If youre looking to reduce inflammation, speed up wound healing, or simply improve your health and wellbeing, the state-of-the-art Aivee Light Therapy can do wonders for your physical state.

Its latest Intravenous Light Therapy treatment is best for inflammation abatement, pathogen deactivation, bloodstream cleansing and pain reduction. This is highly recommended for immune system modulation, cell regeneration and neuron repair.

It also increases stem cell proliferation, enhances stem cell survivability and stem cell differentiation.

The Aivee Clinic is at Bonifacio Global City, SM Mega Fashion Hall and Alabang. Call 5731420, 0917-7283838; visit http://www.aivee.ph.

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Congressmen seek pro-life focus at NIH – OneNewsNow

By adminJune 22, 2017Embryonic Stem Cells

A move is afoot in Congress to change the direction of the National Institutes of Health to more valuable and humane research projects.

Under the direction of Dr. Francis Collins, NIH has directed millions of dollars toward research on human embryos.

David Prentice of the Charlotte Lozier Institute tells OneNewsNow that Congressmen Jim Banks and Dan Lipinski have introduced the Patients First Act to change the agency's course.

The whole point of the bill," says Prentice, "is to prioritize NIH funding for adult stem cells that are going to be able to help patients, first, in the near term, be able to get them into the clinic and help these people. And that, again, is adult stem cells, not embryonic stem cells."

Dr. Collins is famous for leading the decade-long Human Genome Project, which mapped DNA sequences.

Once an atheist, Collins is also known for being an outspoken Christian in the scientific community, where faith is often mocked and dismissed. Yet the embryonic research at NIH has caused disappointment among pro-life activists, and some have called for his firing at NIH.

The proposed legislation could mean hundreds of millions of dollars would be directed toward adult stem cells, which are already being used to treat medical conditions for an estimated 1.5 million patients around the world.

Shifting research to stem cells is going to help patients, not just mean playing in the laboratory, which is what happens with embryonic stem cells as well as fetal tissue and fetal stem cells, Prentice adds. Embryonic and fetal stem cells have been failures.

Prentice says the latter forms of research are unethical, so instead the money could be spent to accelerate research on something of proven value.

Charlotte Lozier Institute would also like to see bills dealing with other ethical concerns at NIH including animal/human hybrids and research using aborted baby tissue.

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Lab grown human colons change study of GI disease – Medical Xpress

By adminJune 22, 2017Embryonic Stem Cells

June 22, 2017 This confocal microscopic image shows a human colon organoid generated in the laboratory with human pluripotent stem cells. The organoid is shown after it was transplanted into a mouse. The engineered colon secreted proteins found in natural human colon. Researchers report study results in Cell Stem Cell. Credit: Cincinnati Children's

The study is believed to be the first time human colon organoids have been successfully tissue engineered in this manner, according to researchers at Cincinnati Children's Hospital Medical Center who led the project.

The technology allows diseases of the colon to be studied in unprecedented detail in a human modeling system. It also comes with the potential to one day generate human gastrointestinal (GI) tract tissues for transplant into patients, according to James Wells, PhD, senior study investigator and director of the Cincinnati Children's Pluripotent Stem Cell Center.

"Diseases affecting this region of the GI tract are quite prevalent and include ailments like colitis, colon cancer, Irritable Bowel Syndrome, Hirschsprung's disease and polyposis syndromes," Wells said. "We've been limited in how we can study these diseases, including the fact that animal models like mice don't precisely recreate human disease processes in the gastrointestinal tract. This system allows us to very effectively model human diseases and human development."

Building the GI Tract

In a series of studies published since 2009, researchers in Wells' laboratory used human pluripotent stem cells (hPSCs) to grow embryonic-stage small intestines with a functioning nervous system, and the antrum and fundus regions of the human stomach.

The researchers - including Jorge Munera, PhD, first author and postdoctoral fellow in the Wells laboratory - note in their current paper the colon has been more difficult to generate than other parts of the GI tract.

Part of the challenge to identifying the correct genetic and molecular programming to coax hPSCs in to colonic organoids has been a lack of data about embryonic development of the organ, according to the authors. They addressed this by conducting a series of molecular and genetic screens of developing hindgut tissues in animal models. The hindgut is the portion of the developing gut that gives rise to the entire large intestine - which includes the cecum, colon and rectum.

They also mined public databases (GNCPro, TiGER, Human Protein Atlas) to identify molecular markers of the hindgut in the adult colon.

Frogs and Mice at Forefront

To develop a model for generating the human colon, scientists first identified SATB2 (special AT-rich sequence-binding protein 2) as a definitive molecular marker for hindgut in frogs, mice and in humans.

SATB2 is a DNA-binding protein that facilitates structural organization of chromosomes in the nucleus of cells.

The protein sequence of SATB2 is remarkably similar between frogs, mice and humans. This led the authors to the hypothesis that molecular signals regulating SATB2 in frogs and mice could be used to make human colon organoids that express the protein.

The authors also noticed that signaling from the growth factor BMP (bone morphogenetic protein) was highly active in the SATB2-expressing region of the gut tube. The researchers learned during their analysis of frog, mouse and human stem-cell derived intestine that signaling by BMP is needed to establish SATB2 in the developing hindgut. With SABT2 as a marker, the researchers show BMP signaling is required for development of tissues specific to the posterior gut region of frogs and mice where the colon develops.

When BMP protein was added for three days in human pluripotent stem cell-derived gut tube cultures, it induced a posterior HOX code. HOX includes a critical set of genes that help control the embryo's development plan from head to toe. Researchers report the posterior HOX helps control the formation of SATB2-expressing human colon organoids.

Testing Translational Potential

To see how human GI tissues perform in a living organism - and to test their future therapeutic potential - the research team included collaborators from the Division of Surgery, led by Michael Helmrath, MD, a pediatric surgeon and director of the Surgical Research program.

The tissue-engineered colonic organoids were transplanted into the kidney capsules of immunocompromised mice for six to 10 weeks. During observation and analysis of the now in vivo organoids, study authors looked for signs of posterior region enteroendocrine cells, which make hormones found in naturally developed human colon.

Researchers report that following transplant, the human colonic organoids assumed the form, different structures and molecular and cell properties of the human colon.

Munera, study first author, pointed to a number of new ways that human colon organoids could be used study disease.

"By exposing human colonic organoids to inflammatory triggers, we can now learn how the cell lining of the colon and the supporting cells beneath cooperate to respond to inflammation," Munera said. "This could be very relevant for patients with Crohn's disease or ulcerative colitis. And because the microbiome, the organisms that live in our guts, are most concentrated in the colon, the organoids potentially could be used to model the human microbiome in health and disease."

Like other parts of the GI tract grown by the researchers, the human colon organoids also create a potential new platform for testing new drugs before the start of clinical trials. Most oral drugs are absorbed by the body through the gut.

Explore further: Human tissue model developed to test colon cancer drugs

More information: Cell Stem Cell (2017). DOI: 10.1016/j.stem.2017.05.020

The leading cause of acute gastroenteritis linked to eating raw seafood disarms a key host defense system in a novel way: It paralyzes a cell's skeleton, or cytoskeleton.

Fathers-to-be, take note: You may be more useful in the labor and delivery room than you realize.

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Localized signaling islands in cells: New targets for precision drug design – Medical Xpress

By adminJune 22, 2017Uncategorized

June 22, 2017

New research overturns long-held views on a basic messaging system within living cells. Key cellular communication machinery is more regionally constrained within the cell than previously thought. The findings suggest new approaches to designing precision drugs. Localizing drug action at a specific 'address' within the cell could mean fewer side effects in treating cancer, diabetes, heart disease and other serious conditions.

Research results reported this week in the journal Science overturn long-held views on a basic messaging system within living cells.

The findings suggest new approaches to designing precisely targeted drugs for cancer and other serious diseases.

Dr. John D. Scott, professor and chair of pharmacology at the University of Washington School of Medicine and a Howard Hughes Medical Institute Investigator, along with Dr. F. Donelson Smith of the UW and HHMI, led this study, which also involved Drs. Claire and Patrick Eyers and their group at the University of Liverpool.

The researchers explained that key cellular communication machinery is more regionally constrained inside the cell than was previously thought. Communication via this vital system is akin to social networking on your Snapchat account.

Within a cell, the precise positioning of such messaging components allows hormones, the body's chief chemical communicators, to transmit information to exact places inside the cell. Accurate and very local activation of the enzyme that Scott and his group study helps assure a correct response occurs in the right place and at the right time.

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"The inside of a cell is like a crowded city," said Scott, "It is a place of construction and tearing down, goods being transported and trash being recycled, countless messages, (such as the ones we have discovered), assembly lines flowing, and packages moving. Strategically switching on signaling enzyme islands allows these biochemical activities to keep the cell alive and is important to protect against the onset of chronic diseases such as diabetes, heart disease and certain cancers."

Advances in electron microscopy and native mass spectrometry enabled the researchers to determine that a critical component of the signaling system, anchored protein kinase A, remains intact during activation. Parts of the molecule are flexible, allowing it to both contract and stretch, with floppy arms that can reach out to find appropriate targets.

Still, where the molecule performs its act, space is tight. The distance is, in fact, about the width of two proteins inside the cell.

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"We realize that in designing drugs to reach such targets that they will have to work within very narrow confines, " Scott said.

One of his group's collective goals is figuring out how to deliver precision drugs to the right address within this teeming cytoplasmic metropolis.

"Insulating the signal so that the drug effect can't happen elsewhere in the cell is an equally important aspect of drug development because it could greatly reduce side effects," Scott said.

An effort to take this idea of precision medicine a step further is part of the Institute for Targeted Therapeutics at UW Medicine in Seattle. The institute is being set up by Scott and his colleagues in the UW Department of Pharmacology.

The scientists are collaborating with cancer researchers to better understand the molecular causesand possible future treatmentsfor a certain liver malignancy. This particular liver cancer arises from a mutation that produces an abnormal form of the enzyme that is the topic of this current work, protein kinase A, and alters the enzyme's role in cell signaling.

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Other advances that gave the researchers a clearer view of the signaling mechanisms reported in Science include CRISPR gene editing, live-cell imaging techniques, and more powerful ways to look at all components of a protein complex.

Explore further: Study unveils T cell signaling process central to immune response

More information: "Local protein kinase A action proceeds through intact holoenzymes" Science (2017). science.sciencemag.org/cgi/doi/10.1126/science.aaj1669

Journal reference: Science

Provided by: University of Washington

The leading cause of acute gastroenteritis linked to eating raw seafood disarms a key host defense system in a novel way: It paralyzes a cell's skeleton, or cytoskeleton.

Fathers-to-be, take note: You may be more useful in the labor and delivery room than you realize.

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Localized signaling islands in cells: New targets for precision drug design - Medical Xpress

Cells In Fish’s Spinal Discs Repair Themselves – Duke Today

By adminJune 22, 2017Uncategorized

Duke researchers have discovered a unique repair mechanism in the developing backbone of zebrafish that could give insight into why spinal discs of longer-lived organisms like humans degenerate with age.

The repair mechanism apparently protects the fluid-filled cells of the notochord, the precursor of the spine, from mechanical stress as a young fish begins swimming. Notochord cells go on to form the gelatinous center of intervertebral discs, the flat, round cushions wedged between each vertebrae that act as shock absorbers for the spine.

The disappearance of these cells over time is associated with degenerative disc disease, a major cause of human pain and disability worldwide.

It is not difficult to speculate that these same mechanisms of repair and regeneration are present in humans at very early stages, but are lost over time," said Michel Bagnat, Ph.D., senior author of the study and assistant professor of cell biology at Duke University School of Medicine. If we are going to think about techniques that foster intervertebral disc regeneration, this is the basic biology we need to understand.

The study appears June 22, 2017, in Current Biology.

Bagnat likens the notochord to a garden hose filled with water. The hardy structure consists of a sheath of epithelial cells surrounding a collection of giant fluid-filled or vacuolated cells. During development, these vacuolated cells rarely pop, despite being under constant mechanical stress. Recent research has suggested that tiny pouches known as caveolae (Latin for little caves) that form in the plasma membrane of these cells can provide a buffer against stretching or swelling.

To see whether the caveolae protected vacuoles from bursting, his team and collaborators from Germany generated mutants of three caveolar genes in their model organism, the zebrafish. Because these small aquarium fish are transparent as embryos, the scientists could easily visualize any spinal defects triggered by the loss of caveolae.

The researchers found that when the mutant embryos hatched and started swimming, exerting pressure on their underdeveloped backbones, their vacuolated cells started to break up. While the finding confirmed their suspicions, it turned up a puzzling discovery. In the caveolar mutants, you see these serial lesions up and down the notochord, and yet the mature spine formed normally, said Bagnat. That was very puzzling to us.

To figure out how that was possible, lead authors Jamie Garcia and Jennifer Bagwell took a closer look at the notochord of mutant fish. They marked the vacuolated cells green and the surrounding epithelial sheath cells red and then filmed the fish shortly after they hatched and started swimming. First, they could see an occasional vacuolated cell break and spill its contents like a water balloon. Then, over the course of fifteen hours, a nearby epithelial sheath cell would move in, crawl over the detritus of the collapsed cell, and morph into a new vacuolated cell.

They performed a few more experiments and found that the repair response was triggered by the release of the cell contents, specifically the basic molecular building blocks known as nucleotides. The researchers then isolated live epithelial sheath cells and treated them with nucleotide analogs to show that they turned into vacuolated cells.

These cells, which reside in the discs of both zebrafish and man, seem capable of controlling their own repair and regeneration, said Bagnat. Perhaps it is a continuous release of nucleotides that is important for keeping the disc in good shape.

The study may offer insight not only into the development of back and neck pain, but also into the origins of cancer. Their data suggests that chordomas, rare and aggressive notochord cell tumors, may begin when epithelial sheath cells leave the notochord and invade the skull and other tissues.

The research was supported by National Institutes of Health (AR065439, AR065439-04S1, T32DK007568-26, and CA193256), a Capes-Humboldt Fellowship, the Max Planck Society, and a Faculty Scholar grant from the Howard Hughes Medical Institute.

CITATION: "Sheath cell invasion and trans-differentiation repair mechanical damage caused by loss of caveolae in the zebrafish notochord," Jamie Garcia, Jennifer Bagwell, Brian Njaine, James Norman, Daniel S. Levic, Susan Wopat, Sara E. Miller, Xiaojing Liu, Jason W. Locasale, Didier Y.R. Stainier and Michel Bagnat. Current Biology, June 22, 2017. DOI# 10.1016/j.cub.2017.05.035

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Aging-related mutations in blood cells represent major new risk … – Medical Xpress

By adminJune 22, 2017Uncategorized

June 22, 2017 Credit : Susanna M. Hamilton, Broad Communications

Scientists at the Broad Institute of MIT and Harvard have found that a set of genetic mutations in blood cells that arises during aging may be a major new risk factor for cardiovascular disease. In contrast to inherited genetic predispositions and traditional lifestyle risk factors, such as smoking or an unhealthy diet, the new mutations are "somatic mutations" that originate in stem cells in the bone marrow as people age.

Because the mutations are relatively common in older people (over 10% of people over the age of 70 harbor at least one of these mutations), potential future efforts to screen for the mutations in blood cells, identify people at increased risk for coronary heart disease, and reduce risk in those individuals through lifestyle changes or therapeutic interventions could have a significant clinical impact, according to the researchers.

"There is more work to be done, but these results demonstrate that pre-malignant mutations in blood cells are a major cause of cardiovascular disease that in the future may be treatable either with standard therapies or new therapeutic strategies based on these findings," said Benjamin Ebert, a co-senior author of the new study, an institute member at the Broad, a professor of medicine at Harvard Medical School, and a hematologist at Brigham and Women's Hospital.

Featured in the New England Journal of Medicine, the work also contributes to the broader understanding of pathogenesis in coronary heart disease by supporting the hypothesis that inflammation, in addition to elevated cholesterol levels, plays an important role in this illness and potentially other diseases of aging.

"A key finding from this study is that somatic mutations are actually modulating risk for a common disease, something we haven't seen other than in cancer," said first author Siddhartha Jaiswal, a pathologist at Massachusetts General Hospital and researcher in the Ebert lab. "It opens up interesting questions about other diseases of aging in which acquired mutations, in addition to lifestyle and inherited factors, could modulate disease risk."

Previous research led by Ebert and Jaiswal revealed that some somatic mutations that are able to confer a selective advantage to blood stem cells become much more frequent with aging. They named this condition "clonal hematopoiesis of indeterminate potential," (CHIP), and found that it increases the risk of developing a blood cancer more than 10-fold and it appeared to increase mortality from heart attacks or stroke. In the new study, the researchers analyzed data from four case-control studies on more than 8,000 people and found that having one of the CHIP-related mutations nearly doubled the risk for coronary heart disease, with the mutations conferring an even greater risk in people who have previously had a heart attack before age 50.

While the human genetics data showed a strong association between CHIP and coronary heart disease, the team hoped to uncover the underlying biology. Using a mouse model prone to developing atherosclerosis, the scientists showed that loss of one of the CHIP-mutated genes, Tet2, in bone marrow cells leads to larger atherosclerotic plaques in blood vessels, evidence that this mutation can accelerate atherosclerosis in mice.

Atherosclerosis is believed to be a disease of chronic inflammation that can arise in response to excess cholesterol in the vessel wall. To examine this on a cellular level the team turned to the macrophage, an immune cell found in atherosclerotic plaques that can develop from CHIP stem cells and carry the same mutations. Because Tet2 and other CHIP-related mutations are known to be so-called "epigenetic regulators" that can alter the activity of other genes, the team examined gene expression levels in the Tet2-mutated macrophages from mice. They found that the mutated cells appear to be "hyper-inflammatory" with increased expression of inflammatory molecules that contribute to atherosclerosis. In support of this finding, humans with TET2 mutations also had higher levels of one of these molecules, IL-8, in their blood.

The work demonstrates that CHIP associates with coronary heart disease in humans, that mutation of the CHIP-related gene Tet2 causes atherosclerosis in mice, and that an inflammatory mechanism likely underlies the process. More work is needed to show whether other genes that are mutated in CHIP also lead to increased inflammation. The team is also exploring whether interventions such as cholesterol lowering therapy or anti-inflammatory drugs might have benefit in people with CHIP.

Inflammation is also thought to modulate several other diseases of aging besides cardiovascular disease, such as autoimmune disorders and neurodegenerative disease. Because CHIP also increases in frequency with age, somatic mutations that alter inflammatory processes could influence several diseases of aging, though more work is needed to test this possibility.

"By combining genetic analysis on large cohorts with disease model and gene expression studies, we've been able to confirm the earlier hints of CHIP's surprising role in cardiovascular disease," said co-senior author Sekar Kathiresan, director of the Broad's Cardiovascular Disease Initiative, associate professor of medicine at Harvard Medical School, and director of the Center for Genomic Medicine at Massachusetts General Hospital. "Beyond the mutations that you inherit from your parents, this work reveals a new genetic mechanism for atherosclerosismutations in blood stem cells that arise with aging."

Explore further: A role for mutated blood cells in heart disease?

More information: Siddhartha Jaiswal et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease, New England Journal of Medicine (2017). DOI: 10.1056/NEJMoa1701719

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Sweden Launches Initiative to Establish Center for Cell and Gene Therapy Research – Genetic Engineering & Biotechnology News

By adminJune 22, 2017Uncategorized

Sweden aims to establish a new Center for Advanced Medical Products (CAMP) as part of a SEK 320-million ($36.6-million), 8-year Swedish government initiative to position the country as a leading biologics developer.

Swedish regenerative medicine firm Xintela has been appointed a partner in the 6-year project to establish the CAMP cell and gene therapy research center, with SEK 48 million ($5.5 million) in funding from the countrys innovation agency and research council, Vinnova and Vetenskapsrdet. Xintel said that as one of the CAMP initiative founders, it will work with Swedens universities, research institutes, and with firms including AstraZeneca, GE Healthcare and Pfizer. Xintela will initially act as an advisor for development of the center, but in the longer term expects to benefit from emerging R&D.

It is gratifying that the Swedish government, Vinnova and Vetenskapsrdet acknowledge the huge potential of cell and gene therapy and the strong position that Sweden has in this research field,commented Xintela CEO Evy Lundgren-kerlund. Xintela is one of the companies in Sweden with large development potential in cell therapy, which makes us a natural partner for this project.

In the short term CAMP aims to establish itself as an internationally recognised center for R&D, innovation and clinical practice, and to promote industrial growth and SMEs. Longer-term goals include attracting investment from the global pharmaceutical and biotech sectors.

Xintela is exploiting its XINMARK protein marker technology and XACT (Xintela assay for cell therapy) assay platform to develop an allogeneic mesenchymal stem cell-based therapy for repairing cartilage damage in osteoarthritis, and to progress a tumor-targeting antibody treatment for glioblastoma.

Last month the firm established a collaboration with Germany-based CO.DON, which develops autologous cell therapies for cartilage repair. The firms will work together on the development of Xintelas markers both for a next generation CO.DN cell therapy program and for Xintelas cartilage repair cell therapy product.

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Sweden Launches Initiative to Establish Center for Cell and Gene Therapy Research - Genetic Engineering & Biotechnology News