A team based at Osaka University has conducted the first ever transplant of cardiac muscle cells generated from iPS cells, around the globe, in a clinical trial initiated physician.

A professor in the universitys cardiovascular surgery unit, Yoshiki Sawa, together with his colleagues at the university, in a clinical procedure to verify the efficiency and security of the therapy with the help of induced pluripotent stem cells, intend to transplant heart muscle cell sheets over the time of 3 years into 10 individuals undergoing severe heart malfunction a result of ischemic cardiomyopathy.

The team conducted, the present month, an operation on an individual, in an attempt to take a first step into the project. This operation was successful. The individual has now been moved to a general ward.

It is predicted that the cells on the degradable sheets which attach to the hearts surface will grow and eliminate a protein which has the power to regenerate blood vessels and advance cardiac function. Already, the iPS cells have been stored after being taken from the blood cells of healthy donors.

Every sheet that goes on the hearts surface is 4 to 5 centimeters in width, and 0.1 millimeter in thickness.

The team from Osaka University will be observing the patient throughout the year.

At a news conference, Yoshiki Sawa expressed his hopes of the transplant becoming the medical technology that succeeds in saving as many individuals as it can, since he has come across many lives that he was unable to save.

On Monday, the universitys researchers stated how they chose to carry out a clinical trial in a clinical researchs stead so they could gain timely approval from the health ministry for clinical applications.

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Team based at Osaka University carries out world's first transplant of heart cells generated from iPS cells - Medical Herald

IPS Cell Therapy Comments Off on Team based at Osaka University carries out world’s first transplant of heart cells generated from iPS cells – Medical Herald | January 31st, 2020

NEW YORK Last month, Cytovia Therapeutics unveiled two partnerships in succession: one with the New York Stem Cell Foundation, and one with Justin Eyquem's laboratory at the University of California, San Francisco. These partnerships, which contain a three-year research agreement between the three institutions, will support Cytovia's foray into developing natural killer (NK) cell-based therapies for cancer.

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Cytovia's CAR NK Alliance With NYSCF, UCSF Aims to Overcome Negative Side Effects of CAR T Drugs - Precision Oncology News

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Parkinson's disease comes with slowness, rigidity, tremors, and loss of balance due to an insufficiency of the dopamine that coordinates muscle movement. This disease, of which the rate of diagnosis is rising, occurs when the neurons responsible for producing dopamine malfunction or die. About 500,000 Americans are diagnosed with Parkinson's each year.

Most of the time, Parkinson's disease is a condition of the elderly, diagnosed in people 60 and older. However, about 10% of the time, it's detected in people between 21 and 50. "Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life," says Michele Tagliati, an author of a new study from Cedars-Sinai.

The study of brain cells from Parkinson's younger victims has found that the misbehaving neurons are present long before diagnosis typically taking some 20 or 30 years to produce detectable symptoms and may even be present prior to birth. The revelation raises hope for combatting Parkinson's because there's already an approved drug that can mitigate the damage done by the troublemaking neurons before the disease ever appears.

The research is published in the journal Nature Medicine.

Image source: Kateryna Kon/Shutterstock

The authors' investigation began with an examination of neurons based on cells from young-onset Parkinson's (YOPD) patients who had no known mutations. From the cells, induced pluripotent stem cells (iPSCs) were generated and differentiated into dishes containing cultures of dopamine neurons. Senior study author Clive Svendsen says, "Our technique gave us a window back in time to see how well the dopamine neurons might have functioned from the very start of a patient's life."

The scientists observed lysosomes within the YOPD neurons malfunctioning. Since lysosomes are counted on as "trash cans" for unnecessary or depleted proteins, the castoff chemicals began to pile up. In particular, substantial accumulations of soluble -synuclein, a protein implicated in different types of Parkinson's, were seen.

Says Svendsen, "What we are seeing using this new model are the very first signs of young-onset Parkinson's,"revealing that, "It appears that dopamine neurons in these individuals may continue to mishandle -synuclein over a period of 20 or 30 years, causing Parkinson's symptoms to emerge."

The researchers also saw unexpectedly high levels of the enzyme protein kinase C in its active form, though what that has to do with Parkinson's, if anything, is unknown.

Image source: sruilk/Shutterstock

The researchers tested a number of drugs on the cultures to see if any might address the observed accumulations of -synuclein. (They performed parallel tests of laboratory mice.) One drug, PEP005, which is already approved by the FDA for treating skin pre-cancers, did effectively reduce the -synuclein buildup, both in the iPSCs and the mice.

Since PEP005 is currently administered in gel form for treating skin, the researchers are now exploring how the drug might be modified so it can be delivered directly to the brain. The team also plans follow-on research to see if their findings apply equally to forms of Parkinson's beyond YOPD.

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Can Parkinsons be prevented as it stealthily develops? - Big Think

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Umbilical Cord Blood Banking Market 2020 Global Analysis By CBR Systems, Inc., Cordlife., StemCyte India Therapeutics And Others - Dagoretti News

Bone Marrow Stem Cells Comments Off on Umbilical Cord Blood Banking Market 2020 Global Analysis By CBR Systems, Inc., Cordlife., StemCyte India Therapeutics And Others – Dagoretti News | January 31st, 2020

This weeks Round-up looks to the future, as nanoparticles and stem cell-derived cardiac muscle cells get a closer look. More good news for lovers of yogurt, and a smelly but effective treatment for atherosclerosis as well.

Using stem cells extracted from the patients own blood and skin cells, this Japanese research team completed the first-in-human transplant of cardiac muscle cells derived from pluripotent stem cells. The team achieved this by reprogramming them, reverting them to their embryonic-like pluripotent initial state. I hope that (the transplant) will become a medical technology that will save as many people as possible, as Ive seen many lives that I couldnt save, Yoshiki Sawa, a professor in the Osaka University cardiovascular surgery unit, said in apress report.

Stem Cell-Derived Heart Muscle Transplanted Into Human for First Time: Researchers

Like something from a sci-fi horror novel, this team of researcher examined the role that nanoparticles that eat dead cells and stabilize atherosclerotic plaque may be able to play in the future of atherosclerosis treatment. We found we could stimulate the macrophages to selectively eat dead and dying cells these inflammatory cells are precursor cells toatherosclerosis that are part of the cause of heart attacks, one of the authors said in press release. We could deliver a small molecule inside the macrophages to tell them to begin eating again. The authors noted that after a single-cell RNA sequencing analysis, they observed that the prophagocytic nanotubes decreased inflammatory gene expression linked to cytokine and chemokine pathways in lesional macrophages, thereby treating the cell from the inside out.

Are Nanoparticles Potential Gamechangers for Treating Clogged Arteries?

In this large analysis of more than 120,000 individuals, the authors reported multivariable-adjusted hazard ratios (95% CI for all) for mortality were reduced in regular (more than four servings per week) consumers of yogurt, and there was an inverse relationship between regular consumption and cancer mortality as well as cardiovascular-related mortality in women. In our study, regular yogurt consumption was related to lower mortality risk among women, the authors wrote. Given that no clear doseresponse relation was apparent, this result must be interpreted with caution.

Yogurt Consumption Associated with Reduced Mortality Risk (Plus a Caveat)

This research teamlooked human microphages and compared them to dying cells in a dish. They observed that macrophages reclaim arginine and other amino acids when they eat dead cells, and then use an enzyme to convert arginine to putrescine. The putrescine, in return, activates a protein (Rac1) that causes the macrophage to eat more dead cells, suggesting to the authors that the problem of atherosclerosis may be, in part, a problem of putrescine. The findings, according to the accompanying press release, suggest that the compound could be use to potentially treat conditions with chronic inflammation, such as Alzheimers disease.

The Nose Knows: Pungent Compound Associated with Improvements in Atherosclerotic Plaque

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Cardio Round-up: Nanoparticles and Stem Cells in the Spotlight - DocWire News

Cardiac Stem Cells Comments Off on Cardio Round-up: Nanoparticles and Stem Cells in the Spotlight – DocWire News | January 31st, 2020

Three-dimensional printers have now assembled candy, clothing, and even mouse ovaries. But in the next decade, specialized bioprinters could begin to build functioning human organs in space. It turns out, the minimal gravity conditions in space may provide a more ideal environment for building organs than gravity-heavy Earth.

If successful, space-printed organs could help to shorten transplant waitlists and even eliminate organ rejection. Though they still have a long way to go, researchers at the International Space Station (ISS) hope to eventually assemble organs from adult human cells, including stem cells.

The medical field has only recently embraced 3D printing in general, particularly in biomedical fields like regenerative medicine and prosthetics. So far, these printers have produced early versions of blood vessels, bones, and different types of living tissue by churning out repeated layers of bioinka substance comprised of living human cells and other tissue thats meant to mimic the natural environment that surrounds growing organs.

Recently, researchers are finding that Earth might not be the best environment for growing freestanding organs. Because gravity is constantly pushing down on these delicate structures as they grow, researchers must surround the tissues in scaffolding, which can often debilitate the delicate veins and blood vessels and prevent the soon-to-be organs from growing and functioning properly. Within microgravity, however, soft tissues hold their shape naturally, without the need for surrounding supportan observation thats driven researchers to space.

And one manufacturing lab based in Indiana thinks its tech could play a key role in space. The 3D BioFabrication Facility (BFF) is a specialized 3D printer that uses bioink to build layers several times thinner than human hair. It cost about $7 million to build and employs the smallest print tips in existence.

The brainchild of spaceflight equipment developer Techshot and 3D printer manufacturer nScrypt, the BFF headed to the ISS in July 2019 aboard the SpaceX CRS-18.

Currently, the project focuses on building increasingly thick artificial cardiac tissue and delivering it back to Earth. Once the printed cardiac tissue reaches a certain thickness, it gets harder for researchers to ensure that a printed structures layers effectively grow into one another. Ultimately, though, theyd like the organs to arrive here fully formed.

Printed organs would eventually require vasculature and nerve endings to work properly, though that technology doesnt yet exist.

The next stagetesting heart patches under microscopes and within animalscould span over the next four years. As for whole organs, Techshot claims it plans to begin production after 2025. For now, the project is still in its infancy.

If you were to look at what we printed, it looks very modest, says Techshot vice president of corporate advancement Rich Boling. Its just a cuboid-type shape, this rectangular box. Were just trying to get cells to grow one layer into the next.

Cooking organs like pancakes

Compare the manufacturing process to cooking pancakes, Boling says. The space crew first creates a custom bioink pancake mix with the cells sent from Earth, which they load with syringe-like tools into the BFF.

Researchers then insert a cassette into the BFF containing a bioreactora system that mimics the normal bodily functions essential for growing healthy tissue, like providing nutrients and flushing out waste.

Approximately 200 miles below in Greenville, Indiana, Techshot engineers connect with ISS astronauts on a NASA-enabled secure digital pathway. The linkup allows Techshot to remotely command BFF functions like pump pressure, internal temperature, lighting, and print speed.

Next, the actual printing process occurs within the bioreactor and can take anywhere from moments to hours, depending on the shapes complexity. In the final production step, the cell-culturing ADvanced Space Experiment Processor (ADSEP) cooks the theoretical pancake; essentially, the ADSEP toughens up the printed tissue for its journey back to earth. This step could take anywhere from 12 to 45 days for different tissue types. When completed and hardened, the structure heads home.

The researchers have gone through three testing processes so far, each one getting more exact. This March, theyll begin the third round of experiments.

The bioprinter space race

The BFF lab is the sole team developing this specific type of microgravity bioprinter, Boling says. Theyre not the only ones looking to print human organs in space, though.

A Russian project has also entered the bioprinting space race, however their technique highly differs. Unlike the BFFs bioink layering method, Russian biotechnology laboratory 3D Bioprinting Solutions uses magnetic nanoparticles to produce tissue. An electromagnet creates a magnetic field in which levitating tissue forms the desired structuretechnology that appears ripped from the pages of a sci-fi novel.

After their bioprinter fell victim to an October 2018 spacecraft crash, 3D Bioprinting Solutions rebounded; the team now collaborates with US and Israeli researchers at the ISS. Last month, their crew created the first space-bioprinted bone tissue. Similar to the US project, 3D Bioprinting Solutions aims to manufacture functioning human tissues and organs for transplantation and general repair.

Just because we have the technology to do it, should we do it?

If the 3D BioFabrication Facility prospers in printing working human organs, theyd be subject to thorough regulation here on Earth. The US approval process is stringent for any drug, Rich Boling says, posing a challenge for this unprecedented invention. Techshot predicts at least 10 years for space-printed organs to achieve legal approval, though its an inexact estimate.

Along with regulatory acceptance, human tissue printed in microgravity may encounter societal pushback.

Each country maintains varying laws related to medical transplants. Yet as bioengineering advances into the the final frontier, the international scientific research community may need to shape new guidelines for collaboration among the stars.

As the commercialization of low-Earth orbit continues to ramp up in the next few years, it is certainly true that were going to have to take a very close look at the regulations that apply to that, says International Space Station U.S. National Laboratory interim chief scientist Michael Roberts. And some of those regulations are going to stray into questions related to ethics: Just because we have the technology to do it, should we do it?

Niki Vermeulen, a University of Edinburgh science technology and innovation studies lecturer, has researched the social implications of 3D bioprinting experiments. Like any Earth-bound project, she urges scientists not to get peoples hopes up too early in the process; individuals seeking organ transplants could read about the BFF online and think it could soon be ready to meet their needs.

The most important thing now, I think, is expectation management, Vermeulen says. Because its really quite difficult to do this, and of course we really dont know if its going to work. If it did, it would be amazing.

Another main issue is cost. Like other cutting-edge biotechnology innovations, the organs could also pose a major affordability challenge, she says. Techshot claims that a single space-printed organ could actually cost less than one from a human donor, since some people must pay for a lifetime of anti-rejection meds and/or multiple transplants. Theres currently no telling how long the BFF process would actually take, however, compared to the conventional donor route.

Plus, theres potential health risks for recipients: Techshot chief scientist Eugene Boland says cell manipulation always presents a possibility of genetic mutation. Modified stem cells can potentially cause cancer in recipients, for example.

The team is now working to define and minimize any dangers, he says. The BFF experiment adheres to the FDAs specific regulations for human cells, tissues, and cellular and tissue-based products.

Researchers on the ground now hope to perfect human cell manipulation: Over 100 US clinical trials presently test cultured autologous human cells, and several hundred test cultured stem cells with multiple origins.

What comes next

After the next round of printing tests this March, Techshot will share the bioprinter with companies and research institutions looking to print materials like cartilage, bone, and liver tissue. Theyre currently preparing the bioprinter for these additional uses, Boling says, which could advance health care as a whole.

To speed things up for space crews, Techshot is now building a cell factory that produces multiple cell types in orbit. This technology could cut down the number of cell deliveries between Earth and space.

The ISS has taken in plenty of commercial ventures in recent years, Michael Roberts says, and its getting crowded up there. Space-based experiments ramped up between 40 and 50 years ago, though until recently they mostly prioritized satellite communications and remote observation technology. Since then, satellites have shrunk from bus-sized to smaller than a shoebox.

Roberts has witnessed the scientific areas of interest broaden over the past decade to include medicine. Organizations like the National Institutes of Health are now looking to space to improve treatments, and everything from large pharmaceutical companies to small-scale startups want in.

Theyve got something stuck on every surface up there, he says.

As the ISS runs out of space and exterior attachment points, Roberts predicts that commercial ventures will build new facilities built for specific activities like manufacturing and plant growth. He sees it as a good opportunity for further innovation, since the ISS was originally designed for far more general purposes.

Space, as a whole, may start to look quite different from the first exploration age.

Baby boomers may remember glimpsing at a grainy, black-and-white moon landing five decades ago. Within the same lifetime, they could potentially observe the introduction of space-printed organs.

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Space might be the perfect place to grow human organs - Popular Science

Cardiac Stem Cells Comments Off on Space might be the perfect place to grow human organs – Popular Science | January 31st, 2020

As they do in many areas of medicine, stem cells hold great potential in treating injured spinal cords, but getting them where they need to go is a delicate undertaking. Scientists at the University of California San Diego (UCSD) are now reporting a breakthrough in this area, demonstrating a new injection technique in mice they say can deliver far larger doses of stem cells and avoid some of the dangers of current approaches.

The research focuses on the use of a type of stem cell known as a neural precursor cell, which can differentiate into different types of neural cells and hold great potential in repairing damaged spines. Currently, these are directly injected into the primary cord of nerve fibers called the spinal parenchyma.

As such, there is an inherent risk of (further) spinal tissue injury or intraparechymal bleeding, says Martin Marsala, professor in the Department of Anesthesiology at UCSD School of Medicine.

In experiments on rodents, Marsala and his team have demonstrated a safer and less invasive approach. The scientists instead injected the stem cells in between a protective layer around the spine called the pial membrane and the superficial layers of the spinal cord, a region known as the spinal subpial space.

This injection technique allows the delivery of high cell numbers from a single injection, says Marsala. Cells with proliferative properties, such as glial progenitors, then migrate into the spinal parenchyma and populate over time in multiple spinal segments as well as the brain stem. Injected cells acquire the functional properties consistent with surrounding host cells.

Following these promising early results, the scientists are hopeful that stem cells injected in this way could one day greatly accelerate healing and improve the strength of cell-replacement therapies for several spinal neurodegenerative disorders, including spinal traumatic injury, amyotrophic lateral sclerosis and multiple sclerosis. But first will come experiments on larger animal models closer to the human anatomy in size, which will help them fine tune their technique for the best results.

The goal is to define the optimal cell dosing and timing of cell delivery after spinal injury, which is associated with the best treatment effect, says Marsala.

The research was published in the journal Stem Cells Translational Medicine.

Source: University of California San Diego

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Spinal injury researchers find a sweet spot for stem cell injections - New Atlas

Spinal Cord Stem Cells Comments Off on Spinal injury researchers find a sweet spot for stem cell injections – New Atlas | January 31st, 2020

Scientists have developed the first treatment for pain using human stem cells, which provides lasting relief in mice in a single treatment, without side effects. If the treatment is successful in humans, it could be a major breakthrough in the development of new non-opioid, and non-addictive pain management, the researchers said.

"Nerve injury can lead to devastating neuropathic pain and for the majority of patients there are no effective therapies," said Greg Neely, an associate professor at the University of Sydney in Australia.

"This breakthrough means for some of these patients, we could make pain-killing transplants from their own cells, and the cells can then reverse the underlying cause of pain," Neely said in a statement.

The study, published in the journal Pain, used human induced pluripotent stem cells (iPSCs) derived from bone marrow to make pain-killing cells in the lab.

The iPSCs are cells which can develop into many different cell types in the body during early life, and growth.

The researchers then put the cells into the spinal cord of mice with serious neuropathic pain, caused by damage or disease affecting the nervous system.

"Remarkably, the stem-cell neurons promoted lasting pain relief without side effects," said study co-author Leslie Caron.

"It means transplant therapy could be an effective and long-lasting treatment for neuropathic pain. It is very exciting," Caron said.

Because the researchers can pick where to put the pain-killing neurons, they can target only the parts of the body that are in pain.

"This means our approach can have fewer side effects," said John Manion, a PhD student and lead author of research paper.

The stem cells used were derived from adult blood samples, the researchers noted.

Their next step will be to perform extensive safety tests in rodents and pigs.

They will then move to human patients suffering chronic pain within the next five years.

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First pain treatment using human stem cells developed - THE WEEK

Spinal Cord Stem Cells Comments Off on First pain treatment using human stem cells developed – THE WEEK | January 31st, 2020

As amphibians go, axolotls are pretty cute. These salamanders sport a Mona Lisa half-smile and red, frilly gills that make them look dressed up for a party. You might not want them at your soiree, though: Theyre also cannibals. While rare now in the wild, axolotls used to hatch en masse, and it was a salamander-eat-salamander world. In such a harsh nursery, they evolved or maybe kept the ability to regrow severed limbs.

Their regenerative powers are just incredible, says Joshua Currie, a biologist at the Lunenfeld-Tanenbaum Research Institute in Toronto whos been studying salamander regeneration since 2011. If an axolotl loses a limb, the appendage will grow back, at just the right size and orientation. Within weeks, the seam between old and new disappears completely.

And its not just legs: Axolotls can regenerate ovary and lung tissue, even parts of the brain and spinal cord.

The salamanders exceptional comeback from injury has been known for more than a century, and scientists have unraveled some of its secrets. It seals the amputation site with a special type of skin called wound epithelium, then builds a bit of tissue called the blastema, from which sprouts the new body part. But until recently, the fine details of the cells and molecules needed to create a leg from scratch have remained elusive.

With the recentsequencingandassemblyof the axolotls giant genome, though, and thedevelopment of techniques to modify the creatures genes in the lab,regeneration researchers are now poised to discover those details. In so doing, theyll likely identify salamander tricks that could be useful in human medicine

Already, studies are illuminating the cells involved, and defining the chemical ingredients needed. Perhaps, several decades from now, people, too, might regrow organs or limbs. In the nearer future, the findings suggest possible treatments for ways to promote wound-healing and treat blindness.

The idea of human regeneration has evolved from an if to a when in recent decades, says David Gardiner, a developmental biologist at the University of California, Irvine. Everybody now is assuming that its just a matter of time, he says. But, of course, theres still much to do.

In a working limb, cells and tissues are like the instruments in an orchestra: Each contributes actions, like musical notes, to create a symphony. Amputation results in cacophony, but salamanders can rap the conductors baton and reset the remaining tissue back to order and all the way back to the symphonys first movement, when they first grew a limb in the embryo.

The basic steps are known: When a limb is removed, be it by hungry sibling or curious experimenter, within minutes the axolotls blood will clot. Within hours, skin cells divide and crawl to cover the wound with a wound epidermis.

Next, cells from nearby tissues migrate to the amputation site, forming a blob of living matter. This blob, the blastema, is where all the magic happens, said Jessica Whited, a regenerative biologist at Harvard University, in a presentation in California last year. It forms a structure much like the developing embryos limb bud, from which limbs grow.

This movie shows immune cells, labeled to glow green, moving within a regenerating axolotl fingertip. Scientists know that immune cells such as macrophages are essential for regeneration: When they are removed, the process is blocked.

Finally, cells in the blastema turn into all the tissues needed for the new limb and settle down in the right pattern, forming a tiny but perfect limb. This limb then grows to full size. When all is done, you cant even tell where the amputation occurred in the first place, Whited tellsKnowable Magazine.

Scientists know many of the molecular instruments, and some of the notes, involved in this regeneration symphony. But its taken a great deal of work.

As Currie started as a new postdoc with Elly Tanaka, a developmental biologist at the Research Institute of Molecular Pathology in Vienna, he recalls wondering, Where do the cells for regeneration come from? Consider cartilage. Does it arise from the same cells as it does in the developing embryo, called chondrocytes, that are left over in the limb stump? Or does it come from some other source?

To learn more, Currie figured out a way to watch individual cells under the microscope right as regeneration took place. First, he used a genetic trick to randomly tag the cells he was studying in a salamander with a rainbow of colors. Then, to keep things simple, he sliced off just a fingertip from his subjects. Next, he searched for cells that stuck out say, an orange cell that ended up surrounded by a sea of other cells colored green, yellow and so on. He tracked those standout cells, along with their color-matched descendants, over the weeks of limb regeneration. His observations, reported in the journalDevelopmental Cellin 2016,illuminated several secrets to the regeneration process.

Regenerative biologist Joshua Currie labeled the cells in axolotls with a rainbow of colors, so that he could follow their migration after he amputated the tip of the salamanders fingertips. In this image, three days after amputation, the skin (uncolored) has already covered the wound. (Credit: Josh Currie)

For one thing, cell travel is key. Cells are really extricating themselves from where they are and crawling to the amputation plane to form this blastema, Currie says. The distance cells will journey depends on the size of the injury. To make a new fingertip, the salamanders drew on cells within about 0.2 millimeters of the injury. But in other experiments where the salamanders had to replace a wrist and hand, cells came from as far as half a millimeter away.

More strikingly, Currie discovered that contributions to the blastema were not what hed initially expected, and varied from tissue to tissue. There were a lot of surprises, he says.

Chondrocytes, so important for making cartilage in embryos, didnt migrate to the blastema (earlier in 2016, Gardiner and colleaguesreported similar findings). And certain cells entering the blastema pericytes, cells that encircle blood vessels were able to make more of themselves, but nothing else.

The real virtuosos in regeneration were cells in skin called fibroblasts and periskeletal cells, which normally surround bone. They seemed to rewind their development so they could form all kinds of tissues in the new fingertip, morphing into new chondrocytes and other cell types, too.

To Curries surprise, these source cells didnt arrive all at once. Those first on the scene became chondrocytes. Latecomers turned into the soft connective tissues that surround the skeleton.

How do the cells do it? Currie, Tanaka and collaborators looked at connective tissues further, examining the genes turned on and off by individual cells in a regenerating limb. In a 2018Sciencepaper, the team reported thatcells reorganized their gene activation profileto one almost identical, Tanaka says, to those in the limb bud of a developing embryo.

Muscle, meanwhile, has its own variation on the regeneration theme. Mature muscle, in both salamanders and people, contains stem cells called satellite cells. These create new cells as muscles grow or require repair. In a 2017 study inPNAS, Tanaka and colleagues showed (by tracking satellite cells that were made to glow red) that most, if not all, ofmuscle in new limbs comes from satellite cells.

If Currie and Tanaka are investigating the instruments of the regeneration symphony, Catherine McCusker is decoding the melody they play, in the form of chemicals that push the process along. A regenerative biologist at the University of Massachusetts Boston, she recently published arecipe of sorts for creating an axolotl limb from a wound site. By replacing two of three key requirements with a chemical cocktail, McCusker and her colleagues could force salamanders to grow a new arm from a small wound on the side of a limb, giving them an extra arm.

Using what they know about regeneration, researchers at the University of Massachusetts tricked upper-arm tissue into growing an extra arm (green) atop the natural one (red). (Credit: Kaylee Wells/McCusker Lab)

The first requirement for limb regeneration is the presence of a wound, and formation of wound epithelium. But a second, scientists knew, was a nerve that can grow into the injured area. Either the nerve itself, or cells that it talks to, manufacture chemicals needed to make connective tissue become immature again and form a blastema. In their 2019 study inDevelopmental Biology, McCusker and colleagues guided byearlier work by a Japanese team used two growth factors, called BMP and FGF, to fulfill that step in salamanders lacking a nerve in the right place.

The third requirement was for fibroblasts from opposite sides of a wound to find and touch each other. In a hand amputation, for example, cells from the left and right sides of the wrist might meet to correctly pattern and orient the new hand. McCusckers chemical replacement for this requirement was retinoic acid, which the body makes from vitamin A. The chemical plays a role in setting up patterning in embryos and has long been known to pattern tissues during regeneration.

In their experiment, McCuskers team removed a small square of skin from the upper arm of 38 salamanders. Two days later, once the skin had healed over, the researchers made a tiny slit in the skin and slipped in a gelatin bead soaked in FGF and BMP. Thanks to that cocktail, in 25 animals the tissue created a blastema no nerve necessary.

About a week later, the group injected the animals with retinoic acid. In concert with other signals coming from the surrounding tissue, it acted as a pattern generator, and seven of the axolotls sprouted new arms out of the wound site.

The recipe is far from perfected: Some salamanders grew one new arm, some grew two, and some grew three, all out of the same wound spot. McCusker suspects that the gelatin bead got in the way of cells that control the limbs pattern. The key actions produced by the initial injury and wound epithelium also remain mysterious.

Its interesting that you can overcome some of these blocks with relatively few growth factors, comments Randal Voss, a biologist at the University of Kentucky in Lexington. We still dont completely know what happens in the very first moments.

If we did know those early steps, humans might be able to create the regeneration symphony. People already possess many of the cellular instruments, capable of playing the notes. We use essentially the same genes, in different ways, says Ken Poss, a regeneration biologist at the Duke University Medical Center in Durham who describednew advances in regeneration, thanks to genetic tools, in the 2017Annual Review of Genetics.

Regeneration may have been an ability we lost, rather than something salamanders gained. Way back in our evolutionary past, the common ancestors of people and salamanders could have been regenerators, since at least one distant relative of modern-day salamanders could do it. Paleontologists have discovered fossils of300-million-year-old amphibians with limb deformities typically created by imperfect regeneration.Other members of the animal kingdom, such as certain worms, fish and starfish, can also regenerate but its not clear if they use the same symphony score, Whited says.

These fossils suggest that amphibians calledMicromelerpetonwere regenerating limbs 300 million years ago. Thats because the fossils show deformities, such as fused bones, that usually occur when regrowth doesnt work quite right. (Credit: Nadia B Frbisch et al./Proceedings of the Royal Society B, 2014)

Somewhere in their genomes, all animals have the ability, says James Monaghan, a regeneration biologist at Northeastern University in Boston. After all, he points out, all animals grow body parts as embryos. And in fact, people arent entirely inept at regeneration. We can regrow fingertips, muscle, liver tissue and, to a certain extent, skin.

But for larger structures like limbs, our regeneration music falls apart. Human bodies take days to form skin over an injury, and without the crucial wound epithelium, our hopes for regeneration are dashed before it even starts. Instead, we scab and scar.

Its pretty far off in the future that we would be able to grow an entire limb, says McCusker. I hope Im wrong, but thats my feeling.

She thinks that other medical applications could come much sooner, though such as ways to help burn victims. When surgeons perform skin grafts, they frequently transfer the top layers of skin, or use lab-grown skin tissue. But its often an imperfect replacement for what was lost.

Thats because skin varies across the body; just compare the skin on your palm to that on your calf or armpit. The tissues that help skin to match its body position, giving it features like sweat glands and hair as appropriate, lie deeper than many grafts. The replacement skin, then, might not be just like the old skin. But if scientists could create skin with better positional information, they could make the transferred skin a better fit for its new location.

Monaghan, for his part, is thinking about regenerating retinas for people who have macular degeneration or eye trauma. Axolotls can regrow their retinas (though, surprisingly, their ability to regenerate the lens is limited to hatchlings). He is working with Northeastern University chemical engineer Rebecca Carrier, whos been developing materials for use in transplantations. Her collaborators are testing transplants in pigs and people, but find most of the transplanted cells are dying. Perhaps some additional material could create a pro-regeneration environment, and perhaps axolotls could suggest some ingredients.

Carrier and Monaghan experimented with the transplanted pig cells in lab dishes, and found they were more likely to survive and develop into retinal cells if grown together with axolotl retinas. The special ingredientseems to be a distinct set of chemicals that exist on axolotl, but not pig, retinas.Carrier hopes to use this information to create a chemical cocktail to help transplants succeed. Even partially restoring vision would be beneficial, Monaghan notes.

Thanks to genetic sequencing and modern molecular biology, researchers can continue to unlock the many remaining mysteries of regeneration: How does the wound epithelium create a regeneration-promoting environment? What determines which cells migrate into a blastema, and which stay put? How does the salamander manage to grow a new limb of exactly the right size, no larger, no smaller? These secrets and more remain hidden behind that Mona Lisa smile at least for now.

10.1146/knowable-012920-1

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews.

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What the Axolotl's Limb-Regenerating Capabilities Have to Teach Us - Discover Magazine

Spinal Cord Stem Cells Comments Off on What the Axolotl’s Limb-Regenerating Capabilities Have to Teach Us – Discover Magazine | January 31st, 2020

BOSTON, Jan. 30, 2020 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (NASDAQ: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein p53, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for APR-246 in combination with azacitidine for the treatment of myelodysplastic syndromes (MDS) with a susceptible TP53 mutation.

MDS represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to directly contribute to disease progression and a poor overall prognosis.

Breakthrough Therapy Designation further supports our development program for APR-246 in combination with azacitidine in MDS patients with a TP53 mutation, said Christian S. Schade, Chief Executive Officer of Aprea. Outcomes for MDS patients with a TP53 mutation are poor and there are no current therapeutic options specifically for these patients. We look forward to continued interaction with FDA regarding our ongoing Phase 3 clinical study and our clinical development program to advance APR-246.

The FDAs Breakthrough Therapy Designation is intended to expedite the development and review of a drug candidate that is planned to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints.

About p53 and APR-246

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein by restoring wild-type p53 conformation and function and thereby induce programmed cell death in human cancer cells. Pre-clinical anti-tumor activity has been observed with APR-246 in a wide variety of solid and hematological cancers, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase 1/2 clinical program with APR-246 has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.

A pivotal Phase 3 clinical trial of APR-246 and azacitidine for frontline treatment of TP53 mutant MDS is ongoing. APR-246 has received Orphan Drug and Fast Track designations from the FDA for MDS, and Orphan Drug designation from the EMA for MDS, AML and ovarian cancer.

About Aprea Therapeutics

Aprea Therapeutics Inc., (NASDAQ: APRE) is a biopharmaceutical company headquartered in Boston, Massachusetts with research facilities in Stockholm, Sweden, focused on developing and commercializing novel cancer therapeutics that reactivate the mutant tumor suppressor protein p53. The Companys lead product candidate is APR-246, a small molecule in clinical development for hematologic malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). For more information, please visit the company website at http://www.aprea.com.

The Company may use, and intends to use, its investor relations website at http://www.ir.aprea.com as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.

Forward-Looking Statements

Certain information contained in this press release includes forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials and regulatory submissions. We may, in some cases use terms such as predicts, believes, potential, continue, anticipates, estimates, expects, plans, intends, may, could, might, likely, will, should or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including risks related to the success and timing of our clinical trials or other studies and the other risks set forth in our filings with the U.S. Securities and Exchange Commission, including our Quarterly Report on Form 10-Q. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Corporate Contacts:

Scott M. CoianteSr. Vice President and Chief Financial Officer617-463-9385

Gregory A. KorbelVice President of Business Development617-463-9385

Source: Aprea Therapeutics, Inc.

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Aprea Therapeutics Receives FDA Breakthrough Therapy Designation for APR-246 in Combination with Azacitidine for the Treatment of Myelodysplastic...

Bone Marrow Stem Cells Comments Off on Aprea Therapeutics Receives FDA Breakthrough Therapy Designation for APR-246 in Combination with Azacitidine for the Treatment of Myelodysplastic… | January 30th, 2020

The report helps players and investors to stay in a competent position in the global Cell Transplant market as they gain insights into the market competition, leading segments, top regions, and other vital subjects.

The report on the global Cell Transplant market is just the resource that players need to strengthen their overall growth and establish a strong position in their business. It is a compilation of detailed, accurate research studies that provide in-depth analysis on critical subjects of the global Cell Transplant market such as consumption, revenue, sales, production, trends, opportunities, geographic expansion, competition, segmentation, growth drivers, and challenges.

Get the Sample of this [emailprotected]https://www.qyresearch.com/sample-form/form/1495010/global-cell-transplant-market

As part of geographic analysis of the global Cell Transplant market, the report digs deep into the growth of key regions and countries, including but not limited to North America, the US, Europe, the UK, Germany, France, Asia Pacific, China, and the MEA. All of the geographies are comprehensively studied on the basis of share, consumption, production, future growth potential, CAGR, and many other parameters.

Market Segments Covered:

The key players covered in this studyRegen BiopharmaGlobal Cord Blood CorporationCBR SystemsEscape TherapeuticsCryo-SaveLonza GroupPluristem TherapeuticsStemedica Cell Technology

Market segment by Type, the product can be split intoPeripheral Blood Stem Cells Transplant (PBSCT)Bone Marrow Transplant (BMT)Cord Blood Transplant (CBT)

Market segment by Application, split intoHospitalsClinicsOthers

Regions Covered in the Global Cell Transplant Market:

The Middle East and Africa (GCC Countries and Egypt) North America (the United States, Mexico, and Canada) South America (Brazil etc.) Europe (Turkey, Germany, Russia UK, Italy, France, etc.) Asia-Pacific (Vietnam, China, Malaysia, Japan, Philippines, Korea, Thailand, India, Indonesia, and Australia)

Highlights of the Report Accurate market size and CAGR forecasts for the period 2019-2025 Identification and in-depth assessment of growth opportunities in key segments and regions Detailed company profiling of top players of the global Cell Transplant market Exhaustive research on innovation and other trends of the global Cell Transplant market Reliable industry value chain and supply chain analysis Comprehensive analysis of important growth drivers, restraints, challenges, and growth prospects

The scope of the Report:

The report offers a complete company profiling of leading players competing in the global Cell Transplant market with high focus on share, gross margin, net profit, sales, product portfolio, new applications, recent developments, and several other factors. It also throws light on the vendor landscape to help players become aware of future competitive changes in the global Cell Transplant market.

Get Customized Report in your Inbox within 24 hours @https://www.qyresearch.com/customize-request/form/1495010/global-cell-transplant-market

Strategic Points Covered in TOC:

Chapter 1: Introduction, market driving force product scope, market risk, market overview, and market opportunities of the global Cell Transplant market

Chapter 2: Evaluating the leading manufacturers of the global Cell Transplant market which consists of its revenue, sales, and price of the products

Chapter 3: Displaying the competitive nature among key manufacturers, with market share, revenue, and sales

Chapter 4: Presenting global Cell Transplant market by regions, market share and with revenue and sales for the projected period

Chapter 5, 6, 7, 8 and 9 : To evaluate the market by segments, by countries and by manufacturers with revenue share and sales by key countries in these various regions

About Us:QYResearch always pursuits high product quality with the belief that quality is the soul of business. Through years of effort and supports from huge number of customer supports, QYResearch consulting group has accumulated creative design methods on many high-quality markets investigation and research team with rich experience. Today, QYResearch has become the brand of quality assurance in consulting industry.

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Cell Transplant Market 2020 In Depth Research, Size, Trends and Forecast by 2026 | Regen Biopharma, Global Cord Blood Corporation, CBR Systems -...

Bone Marrow Stem Cells Comments Off on Cell Transplant Market 2020 In Depth Research, Size, Trends and Forecast by 2026 | Regen Biopharma, Global Cord Blood Corporation, CBR Systems -… | January 30th, 2020

Are you over tired-looking winter skin? IMAGE has teamed up with Allure Beauty and Nail Spa to give TWO lucky readers the chance to win an Image SkincareRenewal Ritual Collection to transform your skin and get you spring-ready.

With spring just around the corner, it's time to start prepping our skin for those dewy make-up looks we'll be rocking.

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Win an Image Renewal Ritual Collection worth 140 from Allure - image.ie

Skin Stem Cells Comments Off on Win an Image Renewal Ritual Collection worth 140 from Allure – image.ie | January 30th, 2020

Robots are pathetic. You need only watch a robot soccer fail compilation to see that humans ancient quest to build synthetic replicas of ourselves out of nuts, bolts and wiring has been a bust. Every new, groundbreaking robot inevitably turns out to be an ungodly abomination, either physically inept or utterly incapable of social interaction. Our latest attempt at a full-on humanoid, Sophia, looks like a pre-loved department store mannequin and sounds like a 2007-era chatbot dialed to the VERY DEPRESSED setting. Shed be a walking repudiation of brainless techno-optimism, if she could actually walk.

Even attempts to build simpler, dog-like droids, such as Boston Dynamics Spot, have produced robots barely worthy of the name. They dont look much better than what youd expect from an adult Erector set enthusiasts weekend garage projects. Some people find these things terrifying, but I take my cues from the manufacturers, who seem incredibly proud when one of their creations performs a task as easy as opening a door.

Imitating human intelligence in software has also proven a task more difficult than expected. Despite the well-financed wet dreams of companies like Uber, the automotive industry has begun to quietly admit that truly self-driving cars are going to happen in decades, not just a few years from now. The Blue Brain project, which received a billion euros from the EU in 2013 and promised to simulate a human brain by 2019, did not succeed. Blue Brain seems to have had some success building a 3D atlas of a mouse brain, but the projects supercomputer, which takes up an entire room, is heaving and groaning under the strain of doing the same for a human mind. Valiant efforts to simulate a transparent, one millimetre nematode called C. elegans, ongoing since 2004, have yielded similarly slow progress. C. elegans has 302 neurons. The human brain has 86 billion.

These stuff-ups are endlessly amusing to me. I dont want to mock the engineers who pour thousands of hours into building novelty dogs made of bits of broken toasters, or even the vertiginously arrogant scientists who thought they could simulate the human brain inside a decade. (Inside a decade! I mean, my god!) Well, okay, maybe I do want to mock them. Is it a crime to enjoy watching our cultures systematic over-investment in digital Whiggery get written down in value time and time again?

On the other hand, maybe the people doing this stuff have just figured out that attaching the terms robot or artificial intelligence to whatever youre up to is a great way of attracting investment from rich idiots. Sometimes I feel naive for thinking anyone takes these wild claims seriously, but that is precisely the power of a good ideology. The promises of robotics and AI are so seductive that people suspend their critical faculties. Whether you are a business like Uber striving to eliminate the messy and expensive production input known as human beings, or a normal person desperate for easy transportation or someone to keep your elderly relatives company, the way we talk about robots and AI suggests these smart solutions are just around the corner. Even people with their heads screwed on properly dont seem to understand how credulously the media hypes up their coverage of AI.

What these doomed overreaches represent is a failure to grasp the limits of human knowledge. We dont have a comprehensive idea of how the brain works. There is no solid agreement on what consciousness really is. Is it divine? Is it matter? Can you smoke it? Do these questions even make sense? We dont know the purpose of sleep. We dont know what dreams are for. Sexual dimorphism in the brain remains a mystery. Are you picking up a pattern here? Even the seemingly quotidian mechanical abilities of the human body running, standing, gripping, and so on are not understood with the scientific precision that you might expect. How can you make a convincing replica of something if you dont even know what it is to begin with? We are cosmic toddlers waddling around in daddys shoes, pretending to work at the office by scribbling on the walls in crayon, and then wondering where our paychecks are.

The world is an astonishing place, and the idea that we have in our possession the basic tools needed to understand it is no more credible now than it was in Aristotles day, writes philosopher Thomas Nagel. But accepting this epistemic knuckle sandwich doesnt mean abandoning the pursuit of robotics.

Enter the frogbot, a living machine synthesized by a research team at the Allen Discovery Center at Tufts University in Boston.

Frogbots (called xenobots by their creators, a stupid name I refuse to use), are tiny little artificial animals made out of stem cells from the African clawed frog. They cant do much yet move around on two stumpy legs, carry tiny objects in a pouch but to me, they are stranger and scarier than any robot weve made out of metal and plastic.

A "frogbot" developed by researchers at Tufts University.

There are three basic steps to the frogbot process. First, stem cells that will develop into frog skin and frog heart are grown in a dish. (The proto-heart cells produce rhythmic contractions, which is how the finished frogbots move around.) Second, a computer runs an algorithm that simulates thousands and thousands of different frogbot designs in a virtual environment to see which ones are capable of whatever action you want them to perform. Finally, the designs that are likely to work are physically produced from clusters of stem cells using microsurgery, then let loose in another dish to see what they actually do. So far, they do pretty much whatever we want them to do, within reason.

This is very cool. Even though frogbots are tiny and stupid at the moment, they impress me way more than the conga line of faildroids weve managed to cobble together so far. Of course it makes sense to use materials from existing animals; weve been doing this using selective breeding techniques since the dawn of time. What are pigs or cows or sheep but frogbots built over thousands of years? The key innovation here is modelling selective evolution quickly, instead of standing around like idiots for millenia, waiting for hundreds of generations of dogs to fuck.

It makes perfect sense. Why try to reinvent the wheel when you could simply hijack biological processes that already exist? This is a classically human way of solving a problem, cleverer and yet also lazier than the futile pursuit of purely artificial robotics. A big congratulations to the scientists who figured this out, using only keen wit, a positive attitude, and a gigantic pile of money from the U.S. military research agency.

Yes, naturally this exciting new field of science is being used to develop weapons of war. This, not simply the prospect of new intelligences, is the upsetting thing about groundbreaking developments in robotics and AI. Will frogbots be a military invention that simply slides into everyday life, like the internet, canned food, and microwaves? Or will they be used to administer dangerous MKULTRA hallucinogens to innocent populations America decides are in its way? In a world controlled by a small and powerful elite that can essentially do whatever it wants, were forced to be suspicious of new technologies. Will the frogbot become bigger, smarter, and stronger? Yes, probably. Will it be my comrade? Thats another question entirely.

Eleanor Robertson is a writer and editor from Sydney, Australia.

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Robots don't have to be so embarrassing - The Outline

Skin Stem Cells Comments Off on Robots don’t have to be so embarrassing – The Outline | January 30th, 2020

The 2019 novel coronavirus (2019-nCoV) outbreak has sparked a speedy response, with scientists, physicians, and front-line healthcare professionals analyzing data in real-time in order to share findings and call out misinformation. Today, The Lancet published two new peer-reviewed studies: one which found that the new coronavirus is genetically distinct from human SARS and MERS, related viruses which caused their own outbreaks, and a second which reports clinical observations of 99 individuals with 2019-nCoV.

The first cases of the coronavirus outbreak were reported in late December 2019. In this new study, Nanshan Chen and colleagues analyzed available clinical, demographic, and laboratory data for 99 confirmed coronavirus cases at the Wuhan Jinyintan Hospital between Jan 1 to Jan 20, 2020, with clinical outcomes followed until 25th January.

Chen and colleagues reported that the average age of the 99 individuals with 2019-nCoV is around 55.5 years, where 51 have additional chronic conditions, including cardiovascular and cerebrovascular (blood flow to the brain) diseases. Clinical features of the 2019-nCoV include a fever, cough, shortness of breath, headaches, and a sore throat. 17 individuals went on to develop acute respiratory distress syndrome, resulting in death by multiple organ failure in 11 individuals. However, it is important to note here that most of the 2019-nCoV cases were treated with antivirals (75 individuals), antibiotics (70) and oxygen therapy (75), with promising prognoses, where 31 individuals were discharged as of 25th January.

Based on this sample, the study suggests that the 2019 coronavirus is more likely to affect older men already living with chronic conditions but as this study only includes 99 individuals with confirmed cases, it may not present a complete picture of the outbreak. As of right now, there are over 6,000 confirmed coronavirus cases reported, where a total of 126 individuals have recovered, and 133 have died.

In a second Lancet study, Roujian Lu and their fellow colleagues carried out DNA sequencing on samples, obtained from either a throat swab or bronchoalveolar lavage fluids, from eight individuals who had visited the Huanan seafood market in Wuhan, China, and one individual who stayed in a hotel near the market. Upon sequencing the coronaviruss genome, the researchers carried out phylogenetic analysis to narrow down the viruss likely evolutionary origin, and homology modelling to explore the virus receptor-binding properties.

Lu and their fellow colleagues found that the 2019-nCoV genome sequences obtained from the nine patients were very similar (>99.98% similarity). Upon comparing the genome to other coronaviruses (like SARS), the researchers found that the 2019-nCoV is more closely related (~87% similarity) to two bat-derived SARS-like coronaviruses, but does not have as high genetic similarity to known human-infecting coronaviruses, including the SARS-CoV (~79%) orMiddle Eastern Respiratory Syndrome (MERS) CoV (~50%).

The study also found that the 2019-nCoV has a similar receptor-binding structure like that of SARS-CoV, though there are small differences in certain areas. This suggests that like the SARS-CoV, the 2019-nCoV may use the same receptor (called ACE2) to enter cells, though confirmation is still needed.

Finally, phylogenetic analysis found that the 2019-nCoV belongs to the Betacoronavirus family the same category that bat-derived coronaviruses fall into suggesting that bats may indeed be the 2019-nCoV reservoir. However, the researchers note that most bat species are hibernating in late December, and that no bats were being sold at the Huanan seafood market, suggesting that while bats may be the initial host, there may have been a secondary animal species which transmitted the 2019-nCoV between bats and humans.

Its clear that we can expect new findings from the research community in the coming days as scientists attempt to narrow down the source of the 2019-nCoV.

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My cat's coat is mostly white with dark tabby patches. What's going on? - Massive Science

Skin Stem Cells Comments Off on My cat’s coat is mostly white with dark tabby patches. What’s going on? – Massive Science | January 30th, 2020

The 2019 novel coronavirus (2019-nCoV) outbreak has sparked a speedy response, with scientists, physicians, and front-line healthcare professionals analyzing data in real-time in order to share findings and call out misinformation. Today, The Lancet published two new peer-reviewed studies: one which found that the new coronavirus is genetically distinct from human SARS and MERS, related viruses which caused their own outbreaks, and a second which reports clinical observations of 99 individuals with 2019-nCoV.

The first cases of the coronavirus outbreak were reported in late December 2019. In this new study, Nanshan Chen and colleagues analyzed available clinical, demographic, and laboratory data for 99 confirmed coronavirus cases at the Wuhan Jinyintan Hospital between Jan 1 to Jan 20, 2020, with clinical outcomes followed until 25th January.

Chen and colleagues reported that the average age of the 99 individuals with 2019-nCoV is around 55.5 years, where 51 have additional chronic conditions, including cardiovascular and cerebrovascular (blood flow to the brain) diseases. Clinical features of the 2019-nCoV include a fever, cough, shortness of breath, headaches, and a sore throat. 17 individuals went on to develop acute respiratory distress syndrome, resulting in death by multiple organ failure in 11 individuals. However, it is important to note here that most of the 2019-nCoV cases were treated with antivirals (75 individuals), antibiotics (70) and oxygen therapy (75), with promising prognoses, where 31 individuals were discharged as of 25th January.

Based on this sample, the study suggests that the 2019 coronavirus is more likely to affect older men already living with chronic conditions but as this study only includes 99 individuals with confirmed cases, it may not present a complete picture of the outbreak. As of right now, there are over 6,000 confirmed coronavirus cases reported, where a total of 126 individuals have recovered, and 133 have died.

In a second Lancet study, Roujian Lu and their fellow colleagues carried out DNA sequencing on samples, obtained from either a throat swab or bronchoalveolar lavage fluids, from eight individuals who had visited the Huanan seafood market in Wuhan, China, and one individual who stayed in a hotel near the market. Upon sequencing the coronaviruss genome, the researchers carried out phylogenetic analysis to narrow down the viruss likely evolutionary origin, and homology modelling to explore the virus receptor-binding properties.

Lu and their fellow colleagues found that the 2019-nCoV genome sequences obtained from the nine patients were very similar (>99.98% similarity). Upon comparing the genome to other coronaviruses (like SARS), the researchers found that the 2019-nCoV is more closely related (~87% similarity) to two bat-derived SARS-like coronaviruses, but does not have as high genetic similarity to known human-infecting coronaviruses, including the SARS-CoV (~79%) orMiddle Eastern Respiratory Syndrome (MERS) CoV (~50%).

The study also found that the 2019-nCoV has a similar receptor-binding structure like that of SARS-CoV, though there are small differences in certain areas. This suggests that like the SARS-CoV, the 2019-nCoV may use the same receptor (called ACE2) to enter cells, though confirmation is still needed.

Finally, phylogenetic analysis found that the 2019-nCoV belongs to the Betacoronavirus family the same category that bat-derived coronaviruses fall into suggesting that bats may indeed be the 2019-nCoV reservoir. However, the researchers note that most bat species are hibernating in late December, and that no bats were being sold at the Huanan seafood market, suggesting that while bats may be the initial host, there may have been a secondary animal species which transmitted the 2019-nCoV between bats and humans.

Its clear that we can expect new findings from the research community in the coming days as scientists attempt to narrow down the source of the 2019-nCoV.

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You can add almost anything to improve graphene's function, even bird poop - Massive Science

Skin Stem Cells Comments Off on You can add almost anything to improve graphene’s function, even bird poop – Massive Science | January 30th, 2020

Spinal cord injury (SCI) is a common disease with high incidence, disability rate and treatment cost. microRNA (miR)-200a is reported to inhibit Keap1 to activate Nrf2 signaling. This study aimed to explore the effects of lentivirus-mediated miR-200a gene-modified bone marrow mesenchymal stem cells (BMSCs) transplantation on the repair of SCI in a rat model. BMSCs were isolated from the bone marrow of Sprague-Dawley rats. miR-200a targeting to Keap1 was identified by luciferase-reporter gene assay. The expressions of Keap1, Nrf2, NQO-1, HO-1 and GCLC were detected by Western blotting in SCI rats. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan scale. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured. miR-200a inhibited Keap-1 3 UTR activity in BMSCs. Transplantation of BMSCs with overexpression of miR-200a or si-Keap1increased locomotor function recovery of rats after SCI, while decreased MDA level, increased SOD, CAT activities and Nrf2 expression together with its downstream HO-1, NQO1, GCLC protein expressions in SCI rat. These results indicated that overexpressed miR-200a in BMSCs promoted SCI repair, which may be through regulating anti-oxidative signaling pathway. 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

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Upregulation of microRNA-200a in bone marrow mesenchymal stem cells enhances the repair of spinal cord injury in rats by reducing oxidative stress and...

Spinal Cord Stem Cells Comments Off on Upregulation of microRNA-200a in bone marrow mesenchymal stem cells enhances the repair of spinal cord injury in rats by reducing oxidative stress and… | January 30th, 2020

An international research team, led by physician-scientists at University of California San Diego School of Medicine, describe a new method for delivering neural precursor cells (NSCs) to spinal cord injuries in rats, reducing the risk of further injury and boosting the propagation of potentially reparative cells.NSCs hold great potential for treating a variety of neurodegenerative diseases and injuries to the spinal cord. The stem cells possess the ability to differentiate into multiple types of neural cell, depending upon their environment. As a result, there is great interest and much effort to use these cells to repair spinal cord injuries and effectively restore related functions.

But current spinal cell delivery techniques, said Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine, involve direct needle injection into the spinal parenchyma the primary cord of nerve fibers running through the vertebral column. "As such, there is an inherent risk of (further) spinal tissue injury or intraparechymal bleeding," said Marsala.

The new technique is less invasive, depositing injected cells into the spinal subpial space a space between the pial membrane and the superficial layers of the spinal cord.

"This injection technique allows the delivery of high cell numbers from a single injection," said Marsala. "Cells with proliferative properties, such as glial progenitors, then migrate into the spinal parenchyma and populate over time in multiple spinal segments as well as the brain stem. Injected cells acquire the functional properties consistent with surrounding host cells."

Marsala, senior author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health, and colleagues suggest that subpially-injected cells are likely to accelerate and improve treatment potency in cell-replacement therapies for several spinal neurodegenerative disorders in which a broad repopulation by glial cells, such as oligodendrocytes or astrocytes, is desired.

"This may include spinal traumatic injury, amyotrophic lateral sclerosis and multiple sclerosis," said Ciacci.

The researchers plan to test the cell delivery system in larger preclinical animal models of spinal traumatic injury that more closely mimic human anatomy and size. "The goal is to define the optimal cell dosing and timing of cell delivery after spinal injury, which is associated with the best treatment effect," said Marsala.ReferenceMarsala et al. (2019) Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats. Stem Cells Translational Medicine. DOI: https://doi.org/10.1002/sctm.19-0156

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Injection Innovation May Improve Spinal Cord Repair Research - Technology Networks

Spinal Cord Stem Cells Comments Off on Injection Innovation May Improve Spinal Cord Repair Research – Technology Networks | January 30th, 2020

In the 1986 horror classic The Fly, a scientist played by Jeff Goldblum manages, quite unintentionally, to mix his biology with that of a housefly with gruesome results.

But the real-world mutant fruit flies that scientists used to understand body patterning are almost as bizarre: Flies with legs on their brows instead of antennae. Flies with extra chest sections, complete with duplicate wings. Flies missing big chunks of their heads.

These freaky flies have something in common: Theyre mixing up their head-to-tail body plans. And they earned three scientists the Nobel Prize in Physiology or Medicine in 1995.

Two of the scientists, Eric Wieschaus and Christiane Nsslein-Volhard, conducted a now-famous genetic screen of fruit fly embryos in 1979 and 1980 while working at the European Molecular Biology Laboratory in Heidelberg, Germany. By feeding parent flies a powerful mutagen, they created a horde of larvae with genetic mistakes, including ones that affected how the fly embryo arranges bits of tissue, from head to tail, in sections a process called segmentation. (The pair tell the tale of this landmark experiment in the 2016 Annual Review of Cell and Developmental Biology.)

The other Nobel laureate, Edward Lewis of Caltech, discovered key players, later named Hox genes, that tell these fruit fly segments and other body parts what tissues and structures they should become.

Fruit flies, it turns out, have their own segmentation path, different from ours: They make a big chunk of tissue and then slice it up, like one would a loaf of bread. In contrast, vertebrates (including humans) churn out segments one by one, like a string of sausages, as they build the tissue. But many of the genes involved Hox and others found later are the same.

A landmark genetics screen by two scientists unearthed mutants with segmentation defects in the fruit fly Drosophila. On the left is the outer layer, or cuticle, of a normal early larva. To the right are ones of various mutants, with clear abnormalities.

CREDIT: E. WIESCHAUS & C. NSSLEIN-VOLHARD / AR CELL AND DEVELOPMENTAL BIOLOGY 2016

These commonalities extend to the need for a sort of ruler that guides segmentation and Hox actions by helping cells identify their position in the body. That ruler takes the form of a two-way gradient. Cells closest to the head end make lots of a chemical called retinoic acid, and those at the tail end make two other compounds, called FGF and Wnt. These diffuse along the body, such that different spots contain different amounts of the chemicals. So, for example, a cell thats closer to the head than the tail will know its position because its bathed in plenty of retinoic acid, but not so much Wnt or FGF.

Vertebrate segments arise from tissue called the mesoderm. Sandwiched between the cells that will make skin and those that will make most internal organs, the mesoderm will yield tissues such as bone and muscle.

As the embryo grows, part of the mesoderm tissue near the head begins to make its segments in the form of beads of tissue called somites, one on each side of the future spinal cord. They are squeezed out of that mesoderm like toothpaste from a tube, says Robb Krumlauf, a developmental biologist at the Stowers Institute for Medical Research in Kansas City, Missouri. These will turn into vertebrae and skeletal muscles. (Other body parts will develop from cells outside of the segments.)

If the segmentation process goes wrong, vertebrae can take the wrong shape: half-vertebrae, fused vertebrae or wedge-shaped ones, for example. In people, this causes a type of scoliosis, and also may affect the kidneys, heart and other body parts.

How does the embryo make just the right number of segments, all the right size? In the 1970s, English researchers came up with a model they called clock and wavefront. The embryos clock would tick to indicate each time a segment should be produced. The wavefront would consist of a maturation process traveling from head to tail, and cells at the crest of that maturation wave would be ready to segment. Whenever the clock ticked, they would spit out a new segment.

The developing mammalian embryo produces two somites, one each side of the future spinal canal, every time an internal clock ticks. The process is guided by a protein called FGF that is made by the tail end of the embryo and diffuses along its length, forming a gradient. Somite production occurs at a spot (the wave front) where the concentration of FGF is at just the right level when the clock makes a tick. The process repeats itself over and over, gradually building up segments, from which vertebrae and skeletal muscle are made. Two other molecules, Wnt and retinoic acid, also form gradients, and with FGF these are key to telling tissues where they are along an embryos length.

At that time, scientists had no idea what molecules would control either clock or wavefront, or if the theory was even correct. The first hard evidence for a clock came from experiments with chicken eggs, published in 1997.

Developmental biologist Olivier Pourqui, now at Harvard Medical School, was studying the chick version of a gene called hairy that is involved in segmentation in fruit flies. He and his colleagues saw the hairy gene turn on in a cyclical manner: starting out at the tail, and then closer to the head, every 90 minutes. And every 90 minutes, the embryo made a new segment.

That study confirmed that a ticking clock did underlie segmentation, says Michalis Averof, a comparative developmental biologist at CNRS in Lyon, France. In 2012, he reported a similar oscillator in beetles.

Scientists still dont know what sets that clocks pace, but they now know that a variety of other proteins, including two of those ruler proteins, Wnt and FGF (and another called Notch), turn on genes like hairy. The other part of the system the wavefront of maturation is characterized by concentrations of FGF. Since FGF is made at the tail end, levels of the protein will be highest there and lowest at the head. Cells that have a low enough level of FGF when the clock ticks will form a segment.

Changing the speed of the clock can have profound effects on the body plan, as Pourqui found in a 2008 study on snakes. Snakes have hundreds of vertebrae, compared to the few dozen in other vertebrates like chickens, mice and humans. How did this come to be? Compared with that of a mouse, their clock is accelerated, Pourqui found. The faster it ticks, the more segments get made, creating the snakes long spine. He doesnt yet know why the snake clock ticks faster, though.

The bone-and-muscle segments, and the rest of the embryos developing tissues, need instructions so that the ones near the front make shoulders and arms, the ones at the back end make hips and legs, and so on. This process, too, depends on the ruler laid down by retinoic acid, Wnt and FGF. The position of cells with respect to the ruler tells them which Hox genes to activate. The Hox genes then turn on other genes, to make the right size and shape of vertebrae, or a tail, arm, liver, etc.

Its complicated: Mammals have 39 different Hox genes, activated in different combinations along the body and with different parts to play. For example, mice usually grow a defined series of vertebrae, including 13 thoracic segments with ribs and six lumbar segments without. But when scientists bred mice to lack the Hox10 gene, the creatures grew little ribs on the lumbar segments. In rare cases in people, mutations in Hox genes cause diverse effects such as club foot, hair loss and extra fingers and toes.

Lewis, who worked with Hox mutant flies in the 1970s, also discovered a remarkable pattern to the Hox genes. In DNA, they are lined up in the same order in which they are produced, from head to tail, in the embryo. Genes at one end of the line spring into action in response to retinoic acid, with that signal emanating from the head; the other end responds to Wnt and FGF, signals from the rear.

A collection of genes called HOX are activated in different parts of an animals body plan, telling cells and tissues what to become. In the DNA, the genes line up in the same order as they are used in a developing embryo. There are remarkable similarities between the HOX genes of disparate creatures, such as fruit flies, mice and humans. In mammals, the HOX genes diversified so that there are four sets (HOX A, B, C and D) to the flys single set. Duplications also led to an expanded number of HOX genes in each set.

Much remains unknown about how bodies are arranged how the same set of Hox genes creates such different body plans in different animals, for example, and how the pace of the segmentation clock sets just right to make a spine to fit a snake or a mouse or a person. Studying such things in people, of course, is difficult. So Pourqui and colleagues recently turned to human stem cells in a dish.

Using genetic trickery, they engineered the cells to flash yellow every time a certain clock gene turned on. Watching for the yellow glow, the researchers detected a clock that had five hours between each tick. Pourqui now aims to figure out just what controls that five-hour timing.

Its astounding, Krumlauf says, how similar the parts of the body-plan system are across such a wide variety of organisms. Each animal uses many of the same genetic tools, in different ways, to create its own unique shape.

In that respect, then, its not so surprising that Jeff Goldblums character melded so completely with a fly. Wnt, FGF, Hox genes its how we apply them that makes us the creatures we are.

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How do bodies position arms, legs, wings and organs? - Knowable Magazine

Spinal Cord Stem Cells Comments Off on How do bodies position arms, legs, wings and organs? – Knowable Magazine | January 30th, 2020

A team of researchers at Osaka University in Japan successfully transplanted cardiac muscle cells created from iPS into a patient, who is now recovering in the general ward of the hospital.

The team, led by Yoshiki Sawa, a professor in the university's cardiovascular surgery unit, created the cardiac muscle cells from iPS cells in a clinical trial to verify the safety and efficacy of this type of procedure. The researches want to transplant heart muscle cells into ten patients who have serious heart malfunctions because of ischemic cardiomyopathy over a three year period.

RELATED: RESEARCHERS ORGANIZE STEM CELLS BASED ON A COMPUTATIONAL MODEL

Instead of replacing the heart of patients, the researchers developed degradable sheets of heart muscle cells that were placed on the damaged areas of the heart.

To grow the heart muscle cells in the lab, the researchers turned to induced pluripotent stem cells otherwise known as iPS. Researchers are able to take those iPS cells and make them into any cell they want. In this case, it was heart muscle cells.If the clinical trials prove successful it could remove someday the need for heart transplants.

I hope that (the transplant) will become a medical technology that will save as many people as possible, as Ive seen many lives that I couldnt save, Sawa was quoted at a news conference reported the Japan Times.

As for the patient, the team plans to monitor him during the next year to ascertain how the heart muscle cells perform. According to the Japan Times, the researchers opted to conduct a clinical trial instead of a clinical study because they want approval from Japan's health ministry for clinical application as soon as possible.

The report noted that during the trial the researchers will look at risks, probabilities of cancer and the efficacy of transplanting 100 million cells for each patient that could include tumor cells.

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Heart Muscle Cells Made in the Lab Successfully Transplanted into Patient - Interesting Engineering

Cardiac Stem Cells Comments Off on Heart Muscle Cells Made in the Lab Successfully Transplanted into Patient – Interesting Engineering | January 30th, 2020

Biomedical researchers from Texas Tech University Health Sciences Center El Paso and the University of Texas at El Paso are working on a joint project to send miniature 3D bioprinted hearts to space. The research project, which has received backing from the National Science Foundation (NSF), seeks to understand how a microgravity environment affects the function of the human heart.

Bioprinting in space is a growing venture. The microgravity environment found aboard the International Space Station (ISS) provides a unique setting for bioprinted tissues and cellular structures to culture and grow. Bioprinting specialists like CELLINK and 3D Bioprinting Solutions are showcasing the potential of bioprinting in space, both for the advancement of bioprinting technologies and to understand the impact of zero-gravity on the human body.

The three-year research project conducted by the Texas-based research team falls into the latter category. The team, led by Munmun Chattopadhyay, Ph.D., TTUHSC El Paso faculty scientist, and Binata Joddar, Ph.D., UTEP biomedical engineer, wants to understand how the human heart is impacted by microgravity by testing bioprinted cardiac organoids aboard the ISS.

The cardiac organoids consist of heart-tissue structures measuring less than 1 mm in thickness which are bioprinted using human stem cells. The organoids will be sent to the ISS, where they will exposed to microgravity environments. This will provide vital insights into a condition commonly experienced by astronauts.

The condition in question is cardiac atrophy and it is caused by a weakening of heart tissue. The condition can lead to other problems, like fainting, irregular heartbeats and even heart failure. Because astronauts often suffer from cardiac atrophy after spending long stints in space, the researchers want to better understand the link.

Cardiac atrophy and a related condition, cardiac fibrosis, is a very big problem in our community, said Dr. Chattopadhyay. People suffering from diseases such as diabetes, muscular dystrophy and cancer, and conditions such as sepsis and congestive heart failure, often experience cardiac dysfunction and tissue damage.

The project, which officially started in September, is currently focused on research design. In this stage of the research, the team is developing bioprinted cardiac organoids and exploring different material compositions using cardiac cells to create heart-like tissue. The second stage of the research will be focused on preparing to launch to organoid to space. The final stage will consist of analyzing data collected during the organoids time in space, once they have returned to Earth.

Dr. Chattopadhyay expressed excitement about the ongoing research project, saying: Knowledge gathered from this study could be used to develop technologies and therapeutic strategies to better combat tissue atrophy experienced by astronauts, as well as open the doorforimproved treatmentsforpeople who suffer from serious heart issues due to illness.

The researchers also hope to engage the community with their research by offering a workshop for K-12 students about their experiments aboard the ISS. The team will also host a seminar for medical students, interns and residents about conducting research in space and on Earth.

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El Paso researchers sending bioprinted mini hearts to ISS - 3DPMN

Cardiac Stem Cells Comments Off on El Paso researchers sending bioprinted mini hearts to ISS – 3DPMN | January 30th, 2020