ORGANOID – Science Magazine

By Gunjan SinhaAug. 23, 2017 , 9:00 AM

UTRECHT, THE NETHERLANDSBy her 50th birthday, Els van der Heijden felt sicker than ever. Born with the hereditary disorder cystic fibrosis (CF), she had managed to work around her illness, finishing college and landing a challenging job in consulting. But Van der Heijden, who lives in a small Dutch town, says she always felt "a dark cloud hanging over my head." When she began feeling exhausted and easily out of breath in 2015, she thought it was the beginning of the end.

Then she read a newspaper article about a child with CF named Fabian whose life had been saved after scientists grew a "mini-organ" from a tissue sample snipped from his colon, one organ that CF affects. Doctors had used the mini-organ to test ivacaftor (Kalydeco), a drug so expensive that Dutch insurers refuse to cover it without evidence that it will help an individual CF patient. No such data existed for Fabian, whose CF was caused by an extremely rare mutation. But his minigut responded to ivacaftor, and he improved within hours of taking it. His insurance eventually agreed to pay for the drug.

Van der Heijden's doctor arranged to have a minigut made for her as well; it responded to a drug marketed as Orkambi that combines ivacaftor and another compound, lumacaftor. Within weeks after she began taking that combination, "I had an enormous amount of energy," she says. "For the first time ever, I felt like my body was functioning like it should."

The life-altering test was developed in the lab of Hans Clevers, director of the Hubrecht Institute here. More than a decade ago, Clevers identified a type of mother cell in the gut that can give birth to all other intestinal cells. With the right nutrition, his team coaxed such stem cells to grow into a 3D, pencil tip-sized version of the gut from which it came. The minigut was functionally similar to the intestine and replete with all its major cell typesan organoid.

That was the start of a revolution. Clevers and others have since grown organoids from many other organs, including the stomach, pancreas, brain, and liver. Easy to manipulate, organoids are clarifying how tissues develop and repair injury. But perhaps most exciting, many researchers say, is their ability to model diseases in new ways. Researchers are creating organoids from tumor cells to mimic cancers and introducing specific mutations into organoids made from healthy tissue to study how cancer arises. And as Clevers's lab has shown, organoids can help predict how an individual will respond to a drugmaking personalized medicine a reality. "It is highly likely that organoids will revolutionize therapy of many severe diseases," says Rudolf Jaenisch, a stem cell scientist at the Massachusetts Institute of Technology in Cambridge.

For Clevers, the bonanza has come as a surprise. A basic biologist at heart, he says he never had real-world applications in mind. "I was always driven by curiosity," he says. "For 25 years we published papers with no practical relevance for anyone on this planet."

Organoids can be used to study how pathogens interact with human tissues. In this lung organoid grown in Hans Clevers's lab, cells colored green are infected with respiratory syncytial virus.

NORMAN SACHS

On a bright July morning at the Hubrecht Institute, Clevers listens patiently to presentations during a weekly lab meeting. One postdoc presents data on her efforts to develop an organoid model for small-cell lung cancer; another reports progress on culturing hormone-secreting organoids from human gut tissue. Whenever their research questions strike him as uninspired, Clevers urges them to be more ambitious: "Why don't you pursue something you don't know?" he asks.

"Hans is capable of raising questions that are not contaminated by the anticipated answer," says Edward Nieuwenhuis, chairman of pediatrics at University Medical Center Utrecht (UMCU) and a good friend. "He has a better nose than most for sniffing around and finding interesting stuff," says Ronald Plasterk, who co-directed the Hubrecht lab with Clevers from 2002 to 2007 and is now the Dutch Minister of the Interior and Kingdom Relations. That approach has earned Clevers many awards. In June, for example, he was inducted into the Orden Pour le Mrite, an elite German order with just 80 members worldwide.

Clevers began his career studying immune cells as a postdoc at the Dana-Farber Cancer Institute in Boston. He landed his first job at UMCU's clinical immunology department in 1989, where he quickly became department head. Most of the work was clinical, such as leukemia diagnostics and blood work for transplants. "But my research interests were always much more basic than the environment that I was in," he says.

In early work, he identified a key molecule, T cell-specific transcription factor 1 (TCF-1), that signals the immune cells known as T lymphocytes to proliferate. Later he found that TCF-1 is part of the larger Wnt family of signaling molecules that's important not only for immune responses, but also for embryonic development and tissue repair. In 1997, his lab team discovered that mice lacking the gene for one of those signals, TCF-4, failed to develop pockets in their intestinal lining called crypts. Soon after, a study with Bert Vogelstein at Johns Hopkins University in Baltimore, Maryland, showed that TCF-4 also helps initiate human colon cancer. Fascinated, Clevers switched his focus from the immune system to the gut.

Inspired by a flurry of research on stem cells at the time, Clevers began hunting for intestinal stem cells. More than 50 years ago, researchers deduced that rodent crypts produce many cells that survive only a few days, suggesting some unidentified, longer-lived source for the cells.

After almost a decade of tedious experiments, Clevers's postdoc Nick Barker struck gold in 2007: He discovered that cells carrying a receptor named LGR5 give rise to all cells in mouse intestines and that molecules in the Wnt pathway signal those cells to divide. Barker later found LGR5-positive cells in other organs as well. In some, the cells were always active; in others, such as the liver, they multiplied only when tissues sensed injury.

At the time, culturing stem cells was notoriously hard, but after combing through previous lab experiments, another postdoc in Clevers's lab, Toshiro Sato, concocted a mix of growth factors that coaxed the gut stem cells to replicate in a dish. He hoped to see a flat layer of cells. But what emerged in 2009 from a single LGR5-positive cell was "a beautiful structure that surprised and intrigued me," says Sato, now at Keio University in Tokyo: a 3D replica of a gut epithelium. The structure self-organized into crypts and finger-shaped protrusions called villi, and it began making its own biochemicals. A paper about the feat was rejected several times before being published. Clevers recalls: "No one wanted to believe it."

Soon, the lab began culturing LGR5-positive cells and growing organoids from the stomach, liver, and other organs. "It was an exciting time, and I really felt like we were on the frontiers of discovery," says another postdoc at the time, Meritxell Huch, now at the Gurdon Institute in Cambridge, U.K. "But we certainly didn't think we were opening a new field."

Organoids, lab-grown miniature versions of organs, are transforming science and medicine. Researchers have grown them from many different organs; they have also created organoids from tumor cells to mimic cancers.

V. ALTOUNIAN/SCIENCE

Captivated by stem cells and their potential to regenerate tissues, other labs were starting to make organoids. A few months before Sato's 2009 paper, Akifumi Ootani, a postdoc in Calvin Kuo's group at Stanford University in Palo Alto, California, reported using a different strategy to grow gut organoids. Kuo's method starts with tissue fragments rather than individual stem cells and grows them in a gel partly exposed to air instead of submerged in nutrient medium. Around the same time, Yoshiki Sasai of the RIKEN Center for Developmental Biology in Kobe, Japan, cultured the first brain organoids, starting not with adult stem cells but with embryonic stem cells. Other researchers grew organoids from induced pluripotent stem cells, which resemble embryonic stem cells but are grown from adult cells.

The various methods create different kinds of organoids, each with advantages and drawbacks. Kuo's organoids contain a mix of cell types, which enables "observation of higher-order behaviors such as muscle contraction," he says. Because those organoids include stroma, a scaffold of connective tissue essential for tumor growth, they may prove better for studying therapies that target the stroma, such as cancer immunotherapy. Clevers's mix of growth factors grows organoids consisting primarily of epithelial cells, so his technique doesn't work for the brain and other organs with few or no epithelial cells. Nor can his organoids be used to test drugs targeting blood vessels or immune cells because organoids have neither.

Both methods can generate organoids from individual patients, producing a personalized minigut in just 1 to 3 weeks. (Although Clevers's organoids originate from adult stem cells, isolating those cells isn't necessary; culturing a tissue fragment with the right nutrients is enough.) The methods are reproducible, and the organoids remain genetically stable in culture; they can also be stored in freezers for years.

In 2013, Clevers and others founded a nonprofit, Hubrecht Organoid Technology (HUB), to market applications. Clevers first proposed using organoids for tissue transplants, says HUB Managing Director Rob Vries. Studies showed that healthy organoids implanted in mice with diseased colons could repair injury. "But we bagged the idea because there were too many regulatory hurdles and the chance of success was low," Vries says.

The idea of enlisting organoids to treat CF came from Jeffrey Beekman, a researcher at UMCU who studies that disease. All Dutch newborns are screened for CF, and colon biopsy samples are taken from babies who test positive. The tissue is tested to gauge how dysfunctional the defective gene is and then stored. Growing organoids from those samples would be relatively simple, argued Beekman, who has since spearheaded the project.

CF can arise from more than 2000 mutations in one gene, which cripple the ion channels that move salt and water through cell membranes. The disease affects all tissues, but the primary symptom is excess mucus in the lungs and gut, causing chest infections, coughing, difficulty breathing, and digestive problems.

Ivacaftor and the combination drug lumacaftor and ivacaftor, both marketed by Vertex Pharmaceuticals in Boston, restore the ion channels' function. But the drugs don't work equally well for everyone, and they have been tested and approved only for people with the most common mutations, together accounting for roughly half of all CF patients. Vertex, which declined to answer questions for this story, has been reluctant to spend millions on trials in patients with rare mutations because the potential payoff is small. And with the price tagboth drugs cost between 100,000 and 200,000 per year in Europehealth services and insurance companies have been unwilling to pay for the medicines for people with those untested mutations.

Van der Heijden falls into that category because only two other people in the Netherlands share her mutation. But when organoids grown from her gut were exposed to lumacaftor and ivacaftor, the organoids swelled like normal gut tissue, a sign that the defective protein was working and that salt and water were flowing through. The result helped persuade Vertex to give her the drug through a compassionate-use program, without payment. (Regulatory agencies require her to be monitored in a clinical trial.) Her side effects included fatigue, nausea, and diarrhea, but after a few months, "it was as if someone opened the curtain and said, Look, the sun is there, come out and play," she says. "And I did."

Cystic fibrosis patient Els van der Heijden received a new drug combination based on organoid tests. Within weeks, "I had an enormous amount of energy," she says.

TESSA NEDEREND

In collaboration with Vertex, HUB has tested ivacaftor on organoids grown from CF patients who had taken part in a clinical trial of that drug. The study confirmed that organoids can predict who will respond to the drug.

HUB has also tested ivacaftor on organoids from 50 patients with nine rare mutations. On the basis of the results, insurers agreed to pay for the drug in six more Dutch patients, and Vertex is following up with the first clinical trial of ivacaftor in CF patients with rare mutations. Meanwhile, HUB is building a biobank, financed by Dutch health insurers, containing organoids from all 1500 Dutch CF patients for testing both existing drugs and new candidates.

"This is the next big thing in CF research," says Eitan Kerem, head of pediatrics at Hadassah Medical Center in Jerusalem, who is building a similar biobank and has launched a trial in patients with rare mutations. Organoids are especially useful because no great animal models for CF exist, Kerem says; ferrets and pigs are sometimes used, but "they are expensive and not available to most researchers."

Drug and biotech companies are now striking deals with HUB to explore organoids in other diseases. The success with CF suggests that they can model other single-gene disorders, such as -1 antitrypsin deficiency, which causes symptoms primarily in the lungs and liver. Some companies are also testing failed drugs on organoids and comparing the results with animal and clinical data, hoping to find ways to predict and avoid such failures.

Cancer is also a major target. By growing organoids from tumor samples, researchers can create minitumors and use them to study how cancer develops or to test drugs. Soon after the minigut paper came out in 2009, David Tuveson, who heads the cancer center at Cold Spring Harbor Laboratory in New York, began prodding Clevers to develop organoids for pancreatic cancer, which is notoriously hard to treat. Existing cell culture models were not very realistic, Tuveson says, and creating genetically engineered mice took up to a year, compared with up to 3 weeks for pancreatic cancer organoids.

The organoids have already helped clarify new pathways that lead to pancreatic cancer, Tuveson says, and unpublished data suggest that they will help researchers predict which treatments will be most effective. He and Clevers are trying to make the organoids resemble real cancer more closely by adding stroma and immune cells. The Hubrecht lab is also involved in two trials to assess whether colon cancer organoids grown from individual patients can predict drug response.

Charles Sawyers of Memorial Sloan Kettering Cancer Center in New York City is trying to make prostate cancer organoids, but he says they are finicky. Organoids from primary tumors generally don't grow; those from metastatic tissue sometimes do, but normal cells often outgrow cancer cells. "They seem to need a lot of tender love and care, and there is no method to the madness," says Sawyers, who has succeeded with only 20 patients so far.

But Sawyers discovered that he could easily grow organoids from normal prostate tissue"it just works beautifully," he saysand then use gene-editing techniques such as CRISPR to study any cancer mutation he wants. "Is this a tumor suppressor gene? Is this an oncogene? Does it collaborate with geneXY? You can play the kind of games on the scale that you always wanted to," he says. As Kuo puts it, "We can build cancer from the ground up."

Other cancer researchers want in, too. Tuveson received so many requests for organoid training that he began hosting regular workshops at his laboratory. In 2016, the U.S. National Cancer Institute launched a scheme to develop more than 1000 cell culture models, including organoids, for researchers around the world to use, together with Cancer Research UK in London, the Wellcome Trust Sanger Institute in Hinxton, U.K., and HUB.

Using personalized organoids to treat cancer still faces hurdles. Organoid culture time, which varies by cancer, must be shortened, and the cost, a few thousand dollars per patient, needs to come down. Also, cancers accumulate genetic mutations as they progress, which could mean that an organoid grown from a patient's cancer early on might not reflect its later state. Nevertheless, "from my perspective it's the most transformative advance in cancer research that I know of," Tuveson says.

If all of that excites Clevers, he rarely shows it. He avoids emotional language while discussing his research, preferring instead to describe and explain. Even close friends sometimes find his pragmatism puzzling. "He talks about his research like someone talking about screwing in a screw," Nieuwenhuis says.

Clevers says he gets his high from "the satisfaction of finding something novel," regardless of practical applications. Recent experiments, for instance, suggest that when an organ lacks LGR-5-positive cells, differentiated cells may be able to "dedifferentiate" and repair tissuesa radical change from the one-way street toward specific identities that stem cells were thought to travel. "Some organs may not have a professional stem cell at all," Clevers says, with a hint of wonder. But when asked how he felt when he saw his findings have profound benefits for patients such as Fabian and Els van der Heijden, he simply says, "I did not expect that."

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ORGANOID - Science Magazine

The Adult Brain Can Regenerate Neurons in an Unexpected Area, Says New Study – ScienceAlert

Scientists have discovered for the first time that adult mouse brains produce new cells in the amygdala, a finding that could eventually lead to better treatments for conditions like anxiety and depression, as well as a better understanding of the brain overall.

The amygdala handles a lot of our emotional responses, especially those relating to fear, and broken connections inside it can lead to anxiety disorders such as post-traumatic stress disorder (PTSD).

If the brain is capable of regenerating neurons in the amygdala, then that's potentially one way of fighting back against these mental health issues, according to the team from the University of Queensland in Australia.

"While it was previously known that new neurons are produced in the adult brain, excitingly this is the first time that new cells have been discovered in the amygdala," says one of the team, Pankaj Sah from the Queensland Brain Institute.

"Our discovery has enormous implications for understanding the amygdala's role in regulating fear and fearful memories."

Before now, neurogenesis the process of producing new neurons had only been spotted in human adults in the hippocampus, the part of the brain that handles long-term memory and also deals with emotional responses, and the striatum.

Adult neurogenesis was first recognised in the 1960s, but was more widely accepted in the 1990s, thanks in part to the discovery of stem cells in adult mice brains cells that can divide and develop into other types of cells.

That discovery was made by another team from the Queensland Brain Institute, and since then, scientists have confirmed the same process happens in humans.

Now it looks like it's happening elsewhere too: based on new studies of mice, the researchers found evidence for the same stem cells in the amygdala, cells that could turn into genuine, fully functioning neurons. Now the task is to find the same results in humans.

Right now it's not clear what those new neurons do, or how the brain uses them, but their location is interesting and worthy of further study.

There's so much we still don't know about the brain, though its secrets are slowly being unlocked. As far as neurogenesis goes, for example, we know that a session on the booze slows down the process, though giving up the drink reverses the process.

Meanwhile, a study published in July found that implanting stem cells into the brain can help to extend the lifespan of mice, and it's possible that a similar approach here could also have a positive effect.

"Finding ways of stimulating the production of new brain cells in the amygdala could give us new avenues for treating disorders of fear processing, which include anxiety, PTSD and depression," says one of the team, Dhanisha Jhaveri.

The research has been published in Molecular Psychiatry.

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The Adult Brain Can Regenerate Neurons in an Unexpected Area, Says New Study - ScienceAlert

Want to live longer? Forever Labs wants to help, using your stem cells – Digital Trends

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Why it matters to you

Forever Labs hopes that by storing your stem cells, you can fight disease and slow aging.

We may have found the Fountain of Youth. Or at the very least, weve found Forever Labs. Its a new Y Combinator startup that seeks to help you live longer and healthier by preserving adult stem cells. Because as it turns out, drinking from a mythical source of water is not, in fact, the key to eternity.

While some of us may be familiar with the concept of freezing our eggs, few until now have considered applying the same concept to our stem cells. But this, Forever Labs believes, is a mistake. This is because stem cells can be transformed into any kind of cell the body needs (which is why so much research already exists surrounding these supremely adaptable cells). However, as Forever Labs points out on its website, The number and therapeutic quality of our stem cells diminishes with age. But if you store them, you may be able to preserve them for future use, thereby combating disease and, just maybe, aging.

How does it work? Using a patented device, Forever Labs collects stem cells from your blood marrow, which the team calls a wellspring for stem cells that replenish your blood, bone, immune system, and other vital tissues. The whole process is said to take around 15 minutes, with most clients reporting a five to 10 second pressure-like sensation. And dont worry no scars will result from the process.

Once your cells have been extracted, the company offers to grow and bank your cells for $2,500, as TechCrunch explains. Youll need to pay an extra $250 every year for storing your cells, or if youd rather, just pay a flat fee of $7,000 for life.

If youre looking to get into the storage game earlier rather than later (Forever Labs will start collecting cells as long as youre 18 or over, and suggests that younger is better), then it seems that this $7,000 option might be a bit better. As the loss and decline of bone marrow stem cells continues throughout ones life, Forever Labs notes, and as this decline accelerates with age, storing at anyage may provide benefits to your future self,

So if youre looking for a way to live forever (or just a bit longer), this may be a good way to hedge your bets.

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Want to live longer? Forever Labs wants to help, using your stem cells - Digital Trends

ASC Biosciences, Inc. to appear on the "Informed" series hosted by Rob Lowe – Markets Insider

PALM DESERT, Calif., Aug. 21, 2017 /PRNewswire/ --ASC Biosciences, Inc. (formerly Nevis Capital Corporation) ("ASC") (OTC Pink Open Markets: "ASCW") is pleased to announce it will appear on the award-winning program "Informed" hosted by Rob Lowe.

Informed is an award-winning program that highlights new stories and innovated concepts through ground breaking short-form and long-form documentary presentation. The program, which is anchored by a veteran production team with decades of industry experience, is able to effectively communicate the most critical stories to a wide and diverse audience. "Informed" is hosted by the inimitable Rob Lowe.

ASC Biosciences, Inc. ("ASC" or the "Company") is a development stage biotechnology company that has a proprietary adult stem cell platform capable of forming nearly every tissue in the human body. These cells, Multipotent Adult Stem Cells ("MASCs"), will differentiate into cartilage, bone, tendon, muscle, ligament, fat, blood vessels, nerves, skin, etc. in humans. MASCs have apparent unlimited proliferation potential (do not reach replicative senescence) and have been shown to regenerate tissues by differentiating into the cell types at the site. MASCs lack the ability to cause a rejection response, and can thus be used as an allogenic transplant - which means that cells harvested from a single donor can be expanded in culture and the expanded cells can be used to treat hundreds, thousands, or millions of patients. TheMissionof ASC Biosciences is to provide surgeons around the world with our proprietary brand of unlimited allogeneic "Stem Cells in a Bottle" to be used in a wide variety of FDA Approved orthopedic and cosmetic therapies, resulting in permanent tissue regeneration; thus avoiding the repeat treatments commonly required in the current generation of approved stem cell therapies. ASC intends to establish an intellectual property portfolio that will provide proprietary dominion in the repair and regeneration of all human tissues. For more information visit:http://www.ascbio.comor @ASCbio1 on Facebook.

ASC trades on the OTC Pink Open Markets under the symbol: ASCW.

Forward-Looking StatementsCertain statements contained herein constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on current expectations, estimates and projections about ASC Biosciences, Inc. industry, management's beliefs and certain assumptions made by management. Readers are cautioned that any such forward-looking statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict.

Because such statements involve risks and uncertainties, the actual results and performance of the Company may differ materially from the results expressed or implied by such forward-looking statements. Given these uncertainties, readers are cautioned not to place undue reliance on such forward-looking statements. Unless otherwise required by law, the Company also disclaims any obligation to update its view of any such risks or uncertainties or to announce publicly the result of any revisions to the forward-looking statements made here. Readers should review carefully reports or documents the Company files periodically with the OTC Markets -https://www.otcmarkets.com.

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SOURCE ASC Biosciences, Inc.

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ASC Biosciences, Inc. to appear on the "Informed" series hosted by Rob Lowe - Markets Insider

Adult brains produce new cells in previously undiscovered area – Medical Xpress

August 15, 2017 Credit: Wikimedia Commons

A University of Queensland discovery may lead to new treatments for anxiety, depression and post-traumatic stress disorder (PTSD). UQ Queensland Brain Institute scientists have discovered that new brain cells are produced in the adult amygdala, a region of the brain important for processing emotional memories.

Disrupted connections in the amygdala, an ancient part of the brain, are linked to anxiety disorders such as PTSD.

Queensland Brain Institute director Professor Pankaj Sah said the research marked a major shift in understanding the brain's ability to adapt and regenerate.

"While it was previously known that new neurons are produced in the adult brain, excitingly this is the first time that new cells have been discovered in the amygdala," Professor Sah said.

"Our discovery has enormous implications for understanding the amygdala's role in regulating fear and fearful memories."

Researcher Dr Dhanisha Jhaveri said the amygdala played a key role in fear learningthe process by which we associate a stimulus with a frightening event.

"Fear learning leads to the classic flight or fight responseincreased heart rate, dry mouth, sweaty palmsbut the amygdala also plays a role in producing feelings of dread and despair, in the case of phobias or PTSD, for example," Dr Jhaveri said.

"Finding ways of stimulating the production of new brain cells in the amygdala could give us new avenues for treating disorders of fear processing, which include anxiety, PTSD and depression."

Previously new brain cells in adults were only known to be produced in the hippocampus, a brain region important for spatial learning and memory.

The discovery of that process, called neurogenesis, was made by Queensland Brain Institute founding director Professor Perry Bartlett, who was also involved in the latest research.

"Professor Bartlett's discovery overturned the belief at the time that the adult brain was fixed and unable to change," Professor Sah said. "We have now found stem cells in the amygdala in adult mice, which suggests that neurogenesis occurs in both the hippocampus and the amygdala. "The discovery deepens our understanding of brain plasticity and provides the framework for understanding the functional contribution of new neurons in the amygdala," Professor Sah said.

The research, led by Professor Sah, Professor Bartlett and Dr Jhaveri, is published in Molecular Psychiatry.

Explore further: PTSD may be physical and not only psychological

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Adult brains produce new cells in previously undiscovered area - Medical Xpress

Adult brain’s fear HQ can grow new cells – Cosmos

A new cradle of brain cell formation has been discovered in the adult amygdala, a region that gives memories their emotional bite.

The discovery could lead to a deeper understanding of post-traumatic stress disorder, anxiety, and phobias and also to better treatments.

The formation of freshly minted neurons the cells that send and receive signals in the brain was long thought to be non-existent in adults. But that dogma was overturned in the early 1990s with the discovery of neuron-forming stem cells in the adult hippocampus, a seahorse-shaped region that acts as the brains memory hub. The smell-processing olfactory bulb in rodents, at least also churns out baby neurons throughout life.

Now, the almond-shaped amygdala can be added to this select club.

Our discovery has enormous implications for understanding the amygdala's role in regulating fear and fearful memories," says Pankaj Sah of the Queensland Brain Institute at the University of Queensland, one of the studys lead authors.

The amygdala plays an important role in imbuing memories with emotion. This helps us to learn from our experiences, but the process can go awry in post-traumatic stress disorder, anxiety, or phobias. In these conditions, fear can overwhelm, thanks to an overzealous amygdala.

Researchers have had inklings that the amygdala can make new neurons. But the new work, published in Molecular Psychiatry, is the first to clearly show that stem cells forming in the mouse amygdala grow into bona fide, fully functioning neurons, which is actually pretty revolutionary, says Jee Kim from the Florey Institute of Neuroscience & Mental Health at the University of Melbourne, who was not involved in the study.

The discovery is likely to hold true for the similarly wired human amygdala, says Dhanisha Jhaveri of the Queensland Brain Institute, who co-led the study.

The amygdala only contains a small number of these newborn cells fewer than in the hippocampus. But even small numbers could have a big impact," says Jhaveri.

Thats because the newly formed cells are interneurons, cells that dampen down activity in neural circuits. In the amygdala, these cells help to keep emotions like fear in check.

Now that the fledgling neurons have been discovered, the researchers are working to nut out the pulleys and levers that control their formation. In the hippocampus, exercise and antidepressant drugs can spur new cell formation, whereas stress and inflammation stymy the process.

Similar triggers could affect neurogenesis in the amygdala, too, says Jhaveri. Understanding these triggers, and identifying drugs that specifically encourage new cell formation in the amygdala could ultimately lead to better treatments for anxiety-related disorders.

The finding could also help to explain why exposure therapy, designed to gradually dampen a persons response to a phobia or traumatic memory, works, according to Kim. These neurons may be important in how we learn to reduce our fear, she says.

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Adult brain's fear HQ can grow new cells - Cosmos

Orphan Black is ending, but how far has human cloning come? – The Verge

Orphan Black, the Canadian science fiction show that revolves around human cloning, will end on Saturday, August 12th after five darkly funny, gory seasons. The show began with a former British street urchin, Sarah Manning (Tatiana Maslany), watching as someone with her exact facial features commits suicide by jumping in front of a train. From there, the show unravels to be about large biotech corporations, conspiracies, and above all, morally questionable science.

Spoilers ahead for all of Orphan Black except the finale.

Science classes teach students early on that human experimentation is ethically wrong if the subjects dont know theyre being experimented on, or exactly what the experiment entails. Orphan Black explores this taboo by giving us villains that love experimenting on unwilling or unwitting people. From installing a secret camera in a womans artificial eye to harvesting the eggs of an eight-year-old girl, the corporate forces on the show are unapologetically sinister and indifferent to basic scientific ethics. The show is both a celebration of science and a reminder that its frightening when used to the wrong ends.

maybe Orphan Black can inspire the science thats to come

With the end of Orphan Black imminent, were looking at the real world for our fix of real science straddling the world of science fiction. Since the show began airing in 2013, have we gotten any closer to the future of extreme body modifications and human cloning that Orphan Black has so often teased? I spoke with Paul Knoepfler, a biology professor at UC Davis, and John Quackenbush, professor of biostatistics and computational biology at Harvard and the Dana-Farber Cancer Institute, to see how far away we are from some of the shows most outrageous inventions.

GROWING A TAIL

Early in the shows run, Olivier, a body-modification fan whos one of the antagonists overseeing a human cloning project, shows off the pink tail hes grown. Sarah is understandably disgusted. But such body modifications could exist, as humans are already naturally born with primordial tails, Knoepfler says. All youd need to do is stop the pre-programmed cell death of those tail cells, maybe by giving a pregnant woman a drug, Knoepfler says. The most challenging part of getting a functional tail would be finding a way to extend the length of the spine, according to Quackenbush. And even if a tail was successfully constructed, there are more unknowns, says Knoepfler, like what part of the brain would control it, or whether the tail would trip you as youre walking. Granted, that isnt a problem if its this short:

I SPY WITH MY BIONIC EYE

At the end of season 2, Rachel Duncan, a clone whos grown up under the care of large corporations, is stabbed in the eye. She receives an artificial replacement, and after many months, she regains complete sight. Ultimately, though, she decides to tear out her eye, because she learns the man responsible for commissioning it also had a camera installed inside it to spy on her. This leads to a truly creepy cinematic moment where Rachel sneaks into the mans office, looks down at his mysterious tablet, and discovers a live stream of what her eye sees: a screen within a screen within a screen, ad infinitum. I watched you touch yourself in the shower where you think its clean, the man says gleefully in a following episode.

Putting the shows sinister ingenuity aside for a moment, Rachels bionic eye spy-cam and all may be possible, Knoepfler and Quackenbush say. Bionic eyes already exist, but the main challenge is connecting an artificial eye with the optic nerve, which connects the eye to the brain. That nerve probably would have been damaged during Rachels initial injury. Creating a bionic eye poses an additional challenge, as the eye must mimic nature and be able to send and receive the right kinds of signals to be read by the brain, says Quackenbush. But if the eye and optic nerve could be reconnected, the eye could potentially be powered by a battery, and making a camera small enough to fit inside the eye is completely possible with todays current technology. Then Wi-Fi and Bluetooth would give the eye live-streaming capabilities.

POISONOUS BOT IMPLANT

In the penultimate season, Sarah discovers she has a bot implanted inside her cheek, which acts as a tracking device and contains a poison her enemies can release into her bloodstream. Micro-tracking implantations already exist in our world: just take the microchips that are often implanted in dogs and cats, Quackenbush says. The tracking device part of the bot also seems plausible: there are devices today that can draw on nearby Bluetooth devices as a network, Quackenbush says. And even storing a toxin inside the bot isnt just science fiction, given the steady infusion of insulin or other drugs that devices already offer humans today. The problem, however, is the bots power supply: it would have to be significant enough to potentially sustain the bot throughout a human lifetime and no such batteries exist yet.

AND OF COURSE, CLONING

We already have clones; theyre identical twins, says Quackenbush. But there are other, less random methods for achieving human cloning. One way is how Dolly the sheep was cloned, by taking the part of the egg cell that contains genetic information and replacing it with a donors cell nucleus. The egg is then fertilized and grown into a clone. But using this method, called somatic cell nuclear transfer, on humans could be extremely unsafe, because the clone could have serious developmental disorders, Knoepfler says.

Quackenbush imagines another method to approach human cloning: reversing cell aging. Basically, adult stem cells could be reverted into their original state as stem cells, when they possessed the genetic potential to divide and become the heart, liver, skin, and other organs. An embryo, in many ways, is the ultimate stem cell, says Quackenbush. But this method hasnt been tried before.

No federal laws in the US ban human cloning

Orphan Blacks science consultant, Cosima Herter, believes that cloning humans is illegal in North America. Were not allowed to hear about it, because were not allowed to do it, she wrote in a blog post for the show in 2013. This isnt quite right no federal laws, at least in the US, ban human cloning. The US Food and Drug Administration is the regulator that matters for research into cloning humans.

With the end of Orphan Black comes the end of a decently plausible science fiction series. Its given us hints of what the future might have in store. It could even inspire the science to come. I think [science fiction] is part of what got us into this business in the first place, Quackenbush says of himself, and others in the science community, You see the future and you want to try to invent it.

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Orphan Black is ending, but how far has human cloning come? - The Verge

Is stem cell injection the cure-all miracle? – Health24

08 August 2017 Stem cells are not only used in cancer treatment, but may be effective for a variety of other conditions.

Stem cell therapy has been claimed to cure cancer, improve chronic conditions such as headaches, and even make your skin look younger. How can that not be a good thing?

Youve probably heard about stem cell research before, but what exactly are stem cells, and how can stem cells injected into the body treat various diseases and conditions?

There has been enormous progress in this field over the last few decades, so let's take a look at how stem cell injections work.

What exactly are stem cells?

Stem cells are the bodys building blocks the reserve cells that the body is made up of. These cells are able to produce multiple different cells, each performing a specific function. Stem cells can be divided into two main categories:

What is stem cell therapy?

Stem cell therapy can be categorised as regenerative medicine. Stem cells used in medical treatments are currently harvested from three sources: umbilical cord blood, bone marrow and blood. These are treatments that restore damaged tissue and regenerate new cells in the case of illness or injury.

While there are other forms of stem cell therapy, these are still in the early stages and regarded as research.

How is stem cell therapy performed?

Adult stem cells are derived from a blood sample and injected back into the patient's blood. The surrounding cells are then activated, stimulating rejuvenation in the area.

Why the controversy?

In 2004 South Africa became the first African nation to open a stem cell bank. This involved embryonic stem cells for cloning research and not the "adult" stem cells used in treatment.

Embryonic stem cells are often viewed as problematic, as they are derived from very young foetuses. It is thus viewed as a form of "abortion" to use embryonic stem cells for treatment. But in most cases of stem cell therapy adult stem cells are used, which causes few ethical problems. Stem cells derived from the umbilical cord are not the same as from the embryo.

What does science say?

Prof Jacqui Greenberg from the University of Cape Town stated that although stem cells can potentially treat various diseases, they should be treated with extreme care.

She has no doubt that in time (in medical science particularly, progress is slow and measured in blocks of 10 years), stem cells will be the solution for many things. "But right now we have to strike a balance of not creating too much hype and raising hope too soon. Stem cells are the future, but the future is not now," Greenberg states.

The reason for this is that stem cells derived from an adult are too volatile at times. Researchers are not clear on how many of these stem cells will actually "survive" and "activate" to treat the condition at hand. Therefore it can't be predicted how many cells will survive and become functional.

There is as yet little proof that stem cells can actually fight disease when injected back into the host.Despite the success of IPS cell technology up to date, there are stillchallenges with regard to the purity of stem cells before their use in therapy.

Availability and cost in South Africa

Stem cell therapy is available at various treatment centres in South Africa. One of the most prominent is the South African Stem Cell Institute in the Free State. Here, various treatments, such as regenerative skin treatments and prolotherapy (regeneration of the joints), are offered.

Therapy starts with an initial consultation. During the second consultation vitals are checked, followed by either the fat harvest procedure under tumescent anaesthesia or bone marrow aspiration under local anaesthesia.

The stem cells are then cryopreserved and injected into the patient as needed. Prices of the treatment vary from R500 (for a once-off treatment in a small area, such as the hand) to R22 500 (a comprehensive process), depending on the condition being treated and length of treatment needed. This excludes the initial consultation fee and after-care.

There are also stem cell banks in South Africa, such as Cryo-Save, where stem cells can be stored at an annual fee (excluding initial consultation, testing and harvesting) and used for treatment.

Do your own research

If you do want to go the stem cell route, make sure that the medical programme being offered is legitimate and that the projected outcome is based on real evidence.

There are a number of private institutions banking on the promise of curing any number of diseases with stem cells from a patient's own blood. The truth, however, is that there is no conclusive proof that the majority of these diseases can be cured with the person's own stem cells annihilating the claim that stem cell therapy is the solution to all diseases.

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Is stem cell injection the cure-all miracle? - Health24

Advancells Announces Successful Reversal of Multiple Sclerosis Through Adult Stem Cell Therapy – New Kerala

NOIDA, India, August 4, 2017 : Advancells, an India-based research oriented company today announced successful reversal of Multiple Sclerosis using Adult Stem Cells and Regenerative medicine in the pilot patient of a planned clinical trial.

Patient Rahul Gupta from New Zealand was first diagnosed with MS in 2010 and has had multiple relapses of the disease in the past 7 years. His symptoms had been progressing at a fast pace and he had almost lost his power to walk. This is when he approached India-based Advancells, who have been working in the field of regenerative medicine and research on stem cells for therapeutic usages. The patient was accepted as a trial patient for Advancells unique Adult Stem Cell therapy program and the procedure was carried out in New Delhi in June 2017.

According to Mr. Gupta, "After my last relapse, I became determined to look for alternative treatments for Multiple Sclerosis. I started looking on the net and found that stem cells therapy is a hope for people, suffering with MS. On further research, I found that it is safe and will not harm me in any way. Thus, I was determined to undergo stem cells treatment, as my illness was progressing very quickly."

When contacted, Dr. Lipi Singh, Head of Technology at Advancells commented, "We get approached by a lot of patients from around the world who wish to be a part of our program but we can not take commercials therapies just yet. Patient selection is a key criterion for us and Rahul suited the criterions perfectly. He is young and still at a moderate level of the disease and in a very positive frame of mind. Patients at this stage are best suited for this kind of treatment and thus we decided to accept him as a pilot case."

To perform the therapy, bone marrow of the patient was aspirated and adult stem cells were separated from them. These unmanipulated cells were then reinjected back in the patient at specific points and the patient was put under physiotherapy and dietary routine.

"Straight after the treatment I saw major improvements, I could walk a lot better, could climb stairs (which I was unable to do after 2012) and even go on the treadmill ," reports Rahul.

As per Dr. Lipi Singh, "It will take approximately 3 months for us to review changes in the MRI of the patient but the drastic changes in symptoms clearly are an indication of the fact that the treatment is working and could become a hope for millions of patients across the world, who are suffering from this disease."

Rahul Gupta concludes by saying, "I had to travel all the way from South Pacific Island, New Zealand to Advancells, India to have this treatment done. And trust me; I am very happy with my decision. Right from the start, Advancells team was very professional and knowledgeable. Dr. Lipi gave me great confidence and guided me through the stem cells therapy process and the post treatment options, as well. In fact, she was in regular touch with me for clinical follow ups. This was really of great benefit to me and I found it to be the best part of Advancells, India. Apparently, it is difficult to feel human and valued in some industries and societies - I never felt isolated or like I was just another patient."

"This is a good start to a lengthy research phase but it seems that we are on the right track and hopefully we will be able to make a significant contribution in eradicating not only MS but a host of untreatable diseases existing today, in the future," concludes Dr. Singh.

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Advancells Announces Successful Reversal of Multiple Sclerosis Through Adult Stem Cell Therapy - New Kerala

Gene editing used to repair diseased genes in embryos – NHS Choices

Thursday August 3 2017

The technique means individual genes can be edited

"Deadly gene mutations removed from human embryos in landmark study," reports The Guardian. Researchers have used a gene-editing technique to repair faults in DNA that can cause the often-fatal heart condition, hypertrophic cardiomyopathy.

This inherited heart condition is caused by a genetic change (mutation) in one or more genes. Babies born with hypertrophic cardiomyopathy have diseased and stiff heart muscles, which can lead to sudden unexpected death in childhood and in young athletes; often because they don't realise they have the condition and so put their heart under strain when exercising.

In this latest study researchers used a technique called CRISPR-cas9 to target and then remove faulty genes. CRISPR-cas9 acts like a pair of molecular scissors, allowing scientists to cut out certain sections of DNA. The technique has attracted a great deal of excitement in the scientific community since it was released in 2014. But as yet, there have been no practical applications for human health.

The research is at an early stage and cannot legally be used as treatment to help families affected by hypertrophic cardiomyopathy. And none of the modified embryos were implanted in the womb.

While the technique showed a high degree of accuracy, it's unclear whether it is safe enough to be developed as a treatment. The sperm used in the study came from just one man with faulty genes, so the study needs to be repeated using cells from other people, to be sure the findings can be replicated.

Scientists say it is now important for society to start a discussion about the ethical and legal implications of the technology. It is currently against the law to implant genetically altered human embryos to create a pregnancy, although such embryos can be developed for research.

The study was carried out by researchers from Oregon Health and Science University and the Salk Institute for Biological Studies in the US, the Institute for Basic Science and Seoul University in Korea, and BGI-Shenzen and BGI-Quingdao in China. It was funded by Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation and the Leona M. and Harry B. Helmsley Charitable Trust and the Shenzhen Municipal Government of China. The study was published in thepeer-reviewed journal Nature.

The Guardian carried a clear and accurate report of the study. While thereports fromITV News, Sky News and The Independent were mostly accurate,they over-stated the current stage of research, with Sky News and ITV News saying it could eradicate "thousands of inherited conditions" and the Independent claiming it "opens the possibility for inherited diseases to be wiped out entirely." While this may be possible, we don't know whether other inherited diseases might be as easily targeted as this gene mutation.

Finally, the Daily Mail rolls out the arguably tired clich of the technique leading to "designer babies", which seems irrelevant at this point. The CRISPR-cas9 technique is only in its infancy and (ethics aside) it's simply not possible to use genetic editing to select desirable characteristics most of which are not the result of one single, identifiable gene. No reputable scientist would attempt such a procedure.

This was a series ofexperiments carried out in laboratories, to test the effects of the CRISPR-Cas9 technique on human cells and embryos.

This type of scientific research helps us understand more about genes and how they can be changed by technology. It doesn't tell us what the effects would be if this was used as a treatment.

Researchers carried out a series of experiments on human cells, using the CRISPR-cas9 technique first on modified skin cells, then on very early embryos, and then on eggs at the point of fertilisation by sperm. They used genetic sequencing and analysis to assess the effects of these different experiments on cells and how they developed, up to five days.

They looked specifically to see what proportion of cells carrying faulty mutations could be repaired, whether the process caused other unwanted mutations, and whether the process repaired all, or just some of, thecells in an embryo.

They used skin cells (which were modified into stem cells) and sperm from one man, who carried the MYBPC3 mutation in his genome, and donor eggs from women without the genetic mutation. This is the mutation known to cause hypertrophic cardiomyopathy.

Normally in such cases, roughly half the embryos would have the mutation and half would not, as there's a 50-50 chance of the embryo inheriting the male or female version of the gene.

The CRISPR-cas9 technique can be used to select and delete specific genes from a strand of DNA. When this happens, usually the cut ends of the strand join together, but this causes problems so can't be used in the treatment of humans. The scientists created a genetic template of the healthy version of the gene, which they introduced at the same time as using CRISPR-cas9 to cut the mutated gene. They hoped the DNA would repair itself with a healthy version of the gene.

One important problem with changing genetic material is the development of "mosaic" embryos, where some of the cells have corrected genetic material and others have the original faulty gene. If this happened, doctors would not be able to tell whether or not an embryo was healthy.

The scientists needed to test all the cells in the embryos produced in the experiment, to see whether all cells had the corrected gene or whether the technique had resulted in a mixture.

They also did whole genome sequencing on some embryos, to test for unrelated genetic changes that might have been introduced accidentally during the process.

All embryos in the study were destroyed, in line with legislation about genetic research on embryos.

Researchers found that the technique worked on some of the stem cells and embryos, but worked best when used at the point of fertilisation of the egg. There were important differences between the way the repair worked on the stem cells and the egg.

The researchers found no evidence of mutations induced by the technique, when they examined the cellsin a variety of ways. However, they did find some evidence of gene deletions caused by DNA strands splicing (joining) themselves together without repairing the faulty gene.

The researchers say they have demonstrated how human embryos "employ a different DNA damage repair system" to adult stem cells, which can be used to repair breaks in DNA made using the CRISPR-cas9 gene-editing technique.

They say that "targeted gene correction" could "potentially rescue a substantial portion of mutant human embryos", and increase the numbers available for transfer for couples using pre-implantation diagnosis during IVF treatment.

However, they caution that "despite remarkable targeting efficiency", CRISPR-cas9-treated embryos would not currently be suitable for transfer. "Genome editing approaches must be further optimised before clinical application" can be considered, they say.

Currently, genetically-inherited conditions like hypertrophic cardiomyopathy cannot be cured, only managed to reduce the risk of sudden cardiac death. For couples where one partner carries the mutated gene, the only option to avoid passing it onto their children is pre-implantation genetic diagnosis. This involves using IVF to create embryos, then testing a cell of the embryo to see whether it carries the healthy or mutated version of the gene. Embryos with healthy versions of the gene are then selected for implantation in the womb.

Problems arise if too few or none of the embryos have the correct version of the gene. The researchers suggest their technique could be used to increase the numbers of suitable embryos.

However, the research is still at an early stage and has not yet been shown to be safe or effective enough to be considered as a treatment.

The other major factor is ethics and the law. Some people worry that gene editing could lead to "designer babies," where couples use the tool to select attributes like hair colour, or even intelligence. At present, gene editing could not do this. Most of our characteristics, especially something as complex as intelligence, are not the result of one single, identifiable gene, so could not be selected in this way. And it's likely that, even if gene editing treatments became legally available, they would be restricted to medical conditions.

Designer babies aside, society needs to consider what is acceptable in terms of editing human genetic material in embryos. Some people think that this type of technique is "playing God" or is ethically unacceptable because it involves discarding embryos that carry faulty genes. Others think that it's rational to use the scientific techniques we have developed to eliminate causes of suffering, such as inherited diseases.

This research shows that the questions of how we want to legislate for this type of technique are becoming pressing. While the technology is not there yet, it is advancing quickly. This research shows just how close we are getting to making genetic editing of human embryos a reality.

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Gene editing used to repair diseased genes in embryos - NHS Choices