Ella1977/DreamstimeIn the not too distant future most human babies will be born using eggs and sperm produced from the skin cells of their parents, claims Stanford University law professor and bioethicist Hank Greely in his book, The End of Sex and the Future of Human Reproduction. Basically, Greely is making informed speculation how in vitro gametogenesis (IVG) will progress over the next few years. And considerable progress has been made.

For example, Japanese researchers have turned skin cells from mice into eggs which they fertilized to produce embryos that were implanted into surrogates that then gave birth to healthy mouse pups. In April, Spanish researchers announced that they had made significant progress toward transforming human skin cells into viable sperm.

Harvard bioethicist Glenn Cohen and his colleagues described how "disruptive reproductive technologies" derived from IVG might evolve in a January article in the journal Science Translational Medicine. They go on to assert that "IVG raises vexing ethical and social policy challenges in need of redress."

First let's consider the biomedical benefits of IVG. One result would be the creation of an unlimited supply of early-stage embryos for research. In the reproductive realm, IVG could produce sperm or eggs for people suffering from various forms of infertilty, e.g., congenital and chemotherapy-induced. In addition, IVG could be used to prevent mitochondrial diseases by creating eggs without those mutations and boost regenerative medicine by creating patient-specific stem cell lines that could be used as transplants to replace diseased tissues and organs.

More speculatively, IVG could be used by same sex couples to produce genetically related children. In addition, since skin cells could be used to produce both sperm and eggs, they might be used to create single-parent children (Women wanting a boy would have to find a donated Y-chromosome.) In addition, there is the possibility that someone lift some cells left behind on a glass or comb by a celebrity and turn them into gametes without their permission. Furthermore, the ability to produce unlimited quantities of gametes and embryos will make it feasible to use genome-editing techniques to correct genetic defects and, perhaps, eventually introduce gene variants that could enhance physical and mental functioning.

Glenn and his colleagues observe that some religious believers object to the creation of embryos outside of human bodies and that doctrinaire anti-market folks oppose the "commodification" of human reproduction. Certainly, opponents are entitled to their opinions, but there is no ethical reason why their beliefs should be permitted to interfere with the biomedical and reproductive choices of those who don't agree with them.

Safety concerns will be paramount before rolling out this technology. With regard to reproduction, one benchmark might be that the likelihood of producing birth defects in babies using IVG is no greater than IVF. As I explained in my Designer Babies and Human Enhancement lecture in Moscow:

Greely believes that in about 40 years half of all American babies will born using what he calls Easy PGD. At that time most people will use gametes produced from their skin cells to create scores of IVF embryos that will each have his or her entire genomes sequenced. Prospective parents will then choose among the embryos based on which combination of genetic traits they would prefer. Presumably they would tend avoid those embryos afflicted with debilitating genetic diseases.

Greely believes that Easy PGD will be extremely cheap, e.g., whole genome testing should fall to around $10 by the beginning of the next decade. Easy PGD would also make it possible for same sex couples to have offspring genetically related to both parents and it might even be possible for a person to have both sperm and eggs created from their skin cells, enabling them to be both mother and father of their child.

Interestingly, biologist Craig Venter, the leader of the group that raced the government to a tie in sequencing the human genome, and now founder of the life extension company Human Longevity, Inc. can sequence a fetal genome and give the mother "a picture of what her future child will look like at 18."

"There is a yuck factor here," said Arthur Caplan, a bioethicist at New York University in The New York Times today. "It strikes many people as intuitively yucky to have three parents, or to make a baby without starting from an egg and sperm. But then again, it used to be that people thought blood transfusions were yucky, or putting pig valves in human hearts." Just so.

Naturally, Glenn and his colleagues call for a vigorous ethical debate and government regulation of the technologies. I would gently suggest that a front page article in the Times means that a vigorous public debate is already taking place.

With regard to government regulation - there may be a role for it to the extent that safety issues cannot be handled by developers of the technology. However, the government should certainly stay far, far away from any eugenic efforts to tell people when and what sort of children they may have. The last time the U.S. government started meddling with the reproductive decisions of Americans, it didn't turn out well.

For more background, see my article, "Is Heaven Populated Chiefly by the Souls of Embryos?"

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Skin Cells Into Babies: Bioethicists Freakout Again - Reason (blog)

Brain balls sound like something straight out of a Tim Burton movie: starting as stem cells harvested from patients, they eventually develop into masses of living neurons, jumbled together in misshapen blobs.

Just like the developing brain, these neurons stretch and grow, reaching out skinny branches that grab onto others to form synapsesjunctions where one neuron talks with the next.

And they do talk: previous attempts at growing these brain organoids found that they spark with electrical activity, much like the webs of neurons inside our heads that lead to thoughts and memories.

Theyre creepy. Theyre fascinating. And they may be neuroscientists best bet at modeling developmental disorders like autism in a dish.

Last week, two studies published in the prestigious journal Nature argued for brain balls as a reductionist model for broken brains. In one study, scientists took skin cells from patients with Timothy syndrome, a devastating neurodevelopmental disorder that often ends with childhood death, and grew them into brain balls to study where and how the developing brain veered off track.

In a separate paper, researchers used cutting-edge technology to profile the inhabitants of brain balls as they matured for eight months in a dish. Heres a creepy teaser: some blobs contained retinal neurons that normally allow us to see. Brain balls with eyes?!

As bizarre as that sounds, the fact that brain balls can develop a variety of neuron types with densely packed synapses is a win. Because theyre made from human cells, brain balls may eventually mimic diseases like schizophrenia, autism, or Alzheimers better than mouse models, revealing what went wrong and offering ample test grounds for potential treatments.

Weve never been able to recapitulate these human-brain developmental events in a dish before, says Dr. Sergiu Pasca at Stanford, who led the Timothy syndrome study. Our method lets us see the entire movie, not just snapshots.

Brain balls, better known by their scientific name cerebral organoids, first came onto the neurodevelopmental scene in 2013.

They often begin their short life as run-of-the-mill skin cells. Scientists first transform them back into stem cells. Then, using a chemical concoction of nutrients and signaling molecules, the stem cells are pushed to spontaneously assemble into little Frankenstein blobs of brain tissue.

But the process isnt just random bursts of division and growth. Rather, the way the brain balls mature roughly echoes how a fetuss cortex develops in the womb: the outer edges curl inward, forming outer and deeper layers.

What really sparked scientists interest was this: almost 90 percent of the neurons within a brain ball had active synapses, often spontaneously shooting electrical pulses to others in their network. While scientists believe brain balls arent capable of thinkingthe high-level cognitive processes constantly churning in our headstheyre definitely doing something.

To begin getting some answers, Dr. Paola Arlotta and team at Harvard followed a number of brain balls for nine months as they gradually maturedroughly the amount of time for human gestation, and much longer than any previous attempts.

Periodically, the researchers harvested more than 80,000 brain balls and ran sophisticated genetic tests to figure out their gene expression profile. Like law enforcement using DNA to match a perpetrators identity, this allowed researchers to profile the inhabitants of the organoids.

It was a cellular bonanza: as expected, excitatory neurons and non-neuronal cells called glia both made an appearance. More surprising were inhibitory neurons that dampen network activity, and cells that normally form the corpus callosum, a highway that connects the brains two hemispheres.

But creepiest by far, every single type of retinal cell also made an appearance. Although they couldnt really see in the normal sense, when bathed under light they did fire off electrical signals.

Just like a developing brain, the older they got the more complex the brain balls became. At eight months old, they contained roughly the same density of synapses as a human fetus cortex.

The cells connect witheach other, forming circuits, and once theyre connected, they can synchronize their activity, potentially mimicking higher-order functions of the human brain, says Arlotta.

Thats great, because it means mini brains could be used to study how different types of neurons connect with each other, and how disrupting the process leads to developmental problems.

Thats the direction the second study took. Rather than letting the mini brains grow wild, Pasca and team at Stanford tweaked the protocol to force them into different identities.

As a fetus brain grows, it gradually separates into an outer layer chock full of excitatory neurons, and an inner sanctum where inhibitory neurons reside. A big part of brain wiring is inhibitory neurons reaching out towards the surface and hooking up with their respective partners.

Starting from skin cells collected from patients with Timothy disease, the scientists used distinct chemical concoctions to form two batches of brain balls, each roughly 1/16 of an inch across and containing one million cells. One batch contained mostly inhibitory neurons, mimicking deeper brain regions, whereas the other modeled the cortex.

The spheroid cells were remarkably similar to those from corresponding regions of the human fetal brain, says Dr. J. Gray Camp and Dr. Barbara Treutlein at the Max Planck Institute in Germany, who were not involved in the studies.

The team then stuck the two types of brain blobs together into the same dish, and as expected, the inhibitory ball started nudging its way into the cortical one, until the two fused together.

As it turns out, the inhibitory neurons from Timothy patients were terrible migrants. Rather than smoothly slithering their way into the mesh of excitatory partners, they stuttered, stopped, but somehow ended up much further than theyre supposed to go, as if making up for their inefficiency.

The problem seemed to be the faulty neurons themselves, rather than defective signals from the environment. When researchers fused a Timothy inhibitory ball with a healthy excitatory one, they still fumbled without heads or tails.

But surprisingly, when treated with a chemical normally used for high blood pressure, the Timothy balls calmed down and migrated normally.

Spheroids are opening up new windows through which we can view the normal development of the fetal human brain, says Pasca. More importantly, it will help us see how this goes awry in individual patients.

While the scientists dont know whether the same drug could help babies with Timothy after theyre bornand their basic brain wiring already establishedPasca hopes that there may be a window of opportunity later on in life to correct the misguided migration.

All said, brain balls are an extremely reductionist model of the human brain. Although its hard to say whether the root of Timothy disease is faulty inhibitory neuron migration, its a great place to start looking for answers.

Pasca is rushing to speed up the process of growing spheroids, hoping to develop a giant depository harvested from many patients to screen for drugs that steers them towards a normal developmental path.

Others are a bit more cautious. These new studies show that brain balls whipped up from the same patient or patients with the same disease can express very different genes, warned Camp and Treutlein. The problem is likely more prominent in neurodevelopmental disorders like autism, in which the cause is a lot more heterogeneous.

But the fact that brain organoids behave like actual brains on several fundamental functionsmaking connections, spontaneously firing, responsive to external cuesis promising, so much so that theyre sparking intense ethical debates. Can they eventually see or think? Do they feel? Will consciousness spontaneously emerge without us detecting it?

For now, the mini brains are simply too tiny for higher-level thinking. Only time will tell what theyll eventually become, and how much information these mini brains can provide, says Camp and Treutlein.

Image Credit:PascaLab

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Bizarre Mini Brains Offer a Fascinating New Look at the Brain - Singularity Hub

Injured skin repairs itself with the help of stem cells, but how this process works isnt well understood. A new study proposes that differentiated skin cells turn back into stem cells to heal the wound.

The process is regulated by a protein called Gata6 made by sebaceous duct cells. In response to injury, these cells migrate out into the skin and de-differentiate into stem cells, which then give rise to replacement skin, according to researchers led by Fiona Watt of Kings College London.

The study was published in Nature Cell Biology. When placed online, the study, Wounding induces dedifferentiation of epidermal Gata6 cells and acquisition of stem cell properties, can be found at j.mp/skincells. Watt was senior author. Giacomo Donati, also of Kings College London, was senior author.

Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane, the study stated.

This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.

One of the most-anticipated results of stem cell research would be generation of replacement tissues for those lost by disease or injury. But the potential for immune rejection limits this potential. While immune-matching can be achieved through patient-derived induced pluripotent stem cells, this process takes time and is costly.

Immune-tolerant allogenic stem cells have been produced in a study reported Monday in Nature Biotechnology. These cells were produced by making them express minimally variant human leukocyte antigen class E molecules. Production of these molecules causes a self response that inhibits attack by NK natural killer cells.

When published, the study, HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells, can be found online at j.mp/allogenic. David W Russell was senior author and Germn Gornalusse was first author. Both are of University of Washington, Seattle.

A study conducted in a mouse model of spinal muscular atrophy suggests that symptoms might be reduced by increasing the activity of synapses between sensory and motor neurons. It suggests there may be more than one path to improving or preserving muscle function in SMA patients.

SMA is caused by the deterioration and eventual death of spinal motor neurons. The only treatment shown to affect the underlying course of the disease, Spinraza, was researched by Ionis Pharmaceuticals in Carlsbad and brought to market in a partnership with Biogen.

The study was published Monday in Nature Neuroscience. George Z Mentis was the senior author and Emily V Fletcher was first author. Both are of Columbia University in New York. When placed online, the study, Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy, can be found at j.mp/smanew.

Researchers treated the mice with kainate, which restored near-normal synaptic functioning and improved motor functioning. While the chemical induces seizures, the mice were given doses lower than the seizure threshold.

Because of kainates seizure-inducing potential, the researchers are looking for safer chemicals to stimulate the synaptic connections.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Skin regeneration, universal donor stem cells and new SMA treatment approach - The San Diego Union-Tribune

A team of scientists at the University of Texas Southwestern Medical Center has identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray. The research is published in the journal Genes & Development.

Layers of the skin. Image credit: M.Komorniczak / Madhero / CC BY-SA 3.0.

With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems, said senior author Dr. Lu Le, an associate professor of dermatology with the Harold C. Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center.

Dr. Le and colleagues found that a protein called KROX20 (also termed EGR2), more commonly associated with nerve development, turns on in skin cells that become the hair shaft.

These hair precursor cells then produce a protein called stem cell factor (SCF) that the researchers showed is essential for hair pigmentation.

When the authors deleted the SCF gene (KITLG gene) in the hair progenitor cells in mouse models, the animals hair turned white.

When they deleted the KROX20-producing cells, no hair grew and the mice became bald.

We uncovered this explanation for balding and hair graying while studying a disorder called Neurofibromatosis Type 1, a rare genetic disease that causes tumors to grow on nerves, Dr. Le said.

Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells.

What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF or that cells involved in hair shaft creation make the KROX20 protein.

If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs.

But without SCF, the hair in mouse models was gray, and then turned white with age. Without KROX20-producing cells, no hair grew.

We will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people as well as in male pattern baldness, Dr. Le said.

_____

Chung-Ping Liao et al. Identification of hair shaft progenitors that create a niche for hair pigmentation. Genes & Development, published online May 2, 2017; doi: 10.1101/gad.298703.117

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Skin Cell Discovery Could Lead to Possible Treatments for Balding ... - Sci-News.com

Soon to be a thing of the past?

Iolanda Astor

By Alice Klein

The humble mussel could soon help us prevent scarring. A sticky substance naturally secreted by the marine animal is one element of a glue that closes skin wounds seamlessly in rats. The glue could be used to prevent unsightly scars after accidental cuts or surgical operations.

If this can be replicated in humans, it might be the next big thing for scar therapy, says Allison Cowin at the University of South Australia, who wasnt involved in the study.

Scars form when the collagen scaffolding in skin is broken apart. Instead of re-forming in their original and neat basket-weave arrangement, the collagen fibres grow back in parallel bundles that create the characteristic lumpy appearance of scars.

One way to reduce scarring is to apply decorin, a skin protein involved in collagen organisation. But because decorin has a highly complex physical structure it is hard to synthesise and therefore not used in the clinic.

To get round this problem, Hyung Joon Cha at Pohang University of Science and Technology in South Korea and his colleagues have created a simplified version of decorin. They combined a small section of the decorin protein with a collagen-binding molecule and a sticky substance secreted by mussels.

The resulting glue was tested on rats with deep, 8-millimetre-wide wounds. The glue was spread over each wound and covered with clear plastic film. Rats in a control group had their wounds covered in plastic without any glue.

By day 11, 99 per cent of the wound was closed in the treated rats compared with 78 per cent in the control group. By day 28, treated rats had fully recovered and had virtually no visible scarring. In comparison, control rats had thick, purple scars (see images below).

Jeon EY, Choi B-H, Jung D, Hwang BH, Cha HJ.

Closer inspection under the microscope confirmed that collagen fibres in the treated wounds had returned to their original basket-weave arrangement. The new skin had also developed hair follicles, blood vessels, oil glands and other structures that arent regenerated in scars.

The glue is able to promote normal collagen growth because negative charges on the decorin fragments hold the fibres apart, says Cha. In doing so, the fibres are more easily able to weave in and out between each other instead of sticking together randomly.

Cowin says the results are impressive but there is still a way to go before the results can be translated to humans. Rats have loose skin, whereas we have tight skin, and they tend to heal better and have less scarring than we do, she says. As a result, the glue may not be as effective in people as in rats.

Cha says that the glue will now be tested in pigs, whose skin better resembles our own.

New scar treatments are greatly needed because the existing ones dont work very well, says Cowin. Silicone gels, steroids, pressure bandages, cryotherapy and laser treatments are often used to reduce the appearance of scars, but they cannot erase them completely.

Cowin is developing a scar treatment that uses monoclonal antibodies to block a type of protein that impairs wound healing. Other groups are applying embryonic stem cells to wounds, based on the observation that skin abrasions inembryos and early fetuses dont scar.These approaches are still being tested in animals.

Journal reference: Biomaterials, DOI: 10.1016/j.biomaterials.2017.04.041

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Mussel gloop can be used to make wounds knit without any scars - New Scientist

A fascinating documentary that is making the rounds at film festivals like Tribeca and Cannes gives a rare view of a controversial treatment that more and more Americans are paying up to $50,000 to receive. Stem cell therapy is widely considered to be the next big hope in medicine, with researchers everywhere from Stanford to Johns Hopkins investigating the technologys potential to treat seemingly every ailment known to mankindAlzheimers, cancer, joint injuries, even basic signs of aging. The only hitch: With one tiny exception, it isnt legal in the United States.

We all know the stem cell revolution is occurring outside the U.S., says Brian Mehling, M.D., a Manhattan-based orthopedic surgeon who is certainly doing his part to foment the insurgency. A coproducer of the film, as well as its charismatic recurring subject, Mehling is bringing stem cell tourism into the spotlight and determined to lift the curtain on a medical field that remains mysterious to most. His Blue Horizon medical clinics, with locations in China and Slovakiaand three more set to open in Mexico, Israel, and Jamaicacater to American tourists looking to cutting-edge therapy for help when traditional medicine fails.

Stem cells are the undifferentiated cells that abound in newborns and have the ability to transform into blood, nerve, or muscle cells and aid the body in self-repair. Proselytizers like Mehling say they constitute the latest in holistic medicine, allowing the body to healwithout drugs, surgery, or side effects. At clinics such as Mehlings, doctors either inject the cells, which are generally obtained from umbilical cords during C-sections, into a patients spinal cord (much like an epidural), or administer them via IV drip. The process is alarmingly quick, and patients can typically check out of the facility by the end of the day. One of the few stem-cell therapies approved for use in the United States is one used to treat the blood disease known as beta thalassemia; in that instance, the treatment replaces damaged blood in the immune system and saves tens of thousands of lives each year. Few other stem cell applications, however, have been proven effective in the rigorous clinical trials the Food and Drug Administration requires before signing off on any treatment.

In fact, stem cell clinics remain completely unregulated, and there have been incidents of related troubles. In one recent report , Jim Gass, a resident of San Diego who traveled to stem cell clinics in Mexico, China, and Argentina to help recover from a stroke, later discovered a sizable tumor on his spinal columnand the cancerous cells belonged to somebody else. Troubling cases also emerged at a loosely regulated clinic in Sunrise, Florida where, earlier this spring, three women suffering macular degeneration reported further loss of vision after having stem cells, extracted from their belly fat via liposuction, injected into their eyes. Though, on the whole, reports of treatments at clinics gone awry remain relatively few.

In his film, Stem Cells: The Next Frontier , which is set to appear at Cannes Film Festival this month, Mehling offers a persuasive side of the story, with rapturous testimonials from patients, some of whom who have regained the ability to walk after their stem cell vacations. Added bonus: They come home with better skin, bigger sex drive, and (in the case of at least one balding patient) more hair.

However compelling, there is scant evidence that the injections actually make a difference, and most American doctors caution against buying into the hype. Stem cell researcher Jaime Imitola, M.D. and Ph.D, director of the progressive multiple sclerosis clinic research program at Ohio State University, says he is impressed by the evidence that stem cells can help with neurological disorders in animals. But the question is how can you translate it into clinical trials? We still dont know what were doing when we put stem cells in people.

David Scadden, a professor of medicine and stem cell and regenerative biology at Harvard, and the director of Harvards Stem Cell Institute, says that stem cell tourism is a waste of money for the time being. A world-renowned expert in stem cell science, he remains optimistic about its future applications. Researchers are currently looking into reprogramming, for instance, which effectively converts a mature cell into a stem cell. You rewind its history so it forgets its a blood cell or a skin cell and it rewinds back in time and it can become any cell type, he says. Youd be able to test drugs on these cells, and it could be used to reverse Type 1 diabetes.

For now, though, he does not recommend experimenting with stem cells before we understand them well enough to properlyand safelyharness their benefits. People call me about it all the timethey say, I have this knee thats bugging me, Im going to one of these clinics, he says. His response? For the most part they dont do harm. But nobody Ive spoken with has come back to me and said, You Harvard docs have to get on this . . . . Not yet.

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Stem Cell Tourism Is the Controversial Subject of a New Cannes Documentary - Vogue.com

Men's Health

This Gun Sprays Stem Cells, Helps Burn Victims Grow Skin in Days Men's Health A revolutionary new technique is enabling burn victims to heal quicker, less painfully, and with more normal skin. And it's all thanks to a gun. The SkinGun sprays stem cells onto wounds and allows patients to grow a new, healthy layer of skin in as ...

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This Gun Sprays Stem Cells, Helps Burn Victims Grow Skin in Days - Men's Health

Scientists unveil the UK's largest resource of human stem cells from healthy donors Science Daily The Human Induced Pluripotent Stem Cell Initiative (HipSci) project used standardised methods to generate iPSCs on a large scale to study the differences between healthy people. Reference sets of stem cells were generated from skin biopsies donated by ... and more »

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Scientists unveil the UK's largest resource of human stem cells from healthy donors - Science Daily

A molecular switch has been identified that converts skin cells into cells found in blood vessels, raising hopes of aiding heart disease sufferers.

This technique boosts levels of an enzyme that keeps cells young and could also potentially help cells avoid ageing as they are grown in the lab. Although this technique has been used before, this is the first time it has been understood by scientists.

Some techniques to convert mature skin cells into pluripotent stem cells use a cocktail of chemicals to ensure they turn into designated cell types. Other methods modify cells, skippingthe stem cell state completely. Recently, researchers have been exploring rewinding skin cells so they lose some of their mature cell identity.

Dr Jalees Rehman, who led the study at the University of Illinois at Chicago, said: They dont revert all the way back to a pluripotent stem cell, but instead turn into intermediate progenitor cells. Even though they only differentiate into a few different cell types, progenitor cells can be grown in large quantities, making them suitable for regenerative therapies.

Rehmans research group discovered that progenitor cells could be converted into blood vessel endothelial cells or erythrocytes depending on the level of a gene transcription factor called SOX17. When SOX17 levels were increased, progenitor cells were five times as likely to become endothelial cells. When this process was reversed, fewer endothelial cells but more erythrocytes were produced.

Dr Rehman said: It makes a lot of sense that SOX17 is involved because it is abundant in developing embryos when blood vessels are forming. When human progenitor cells were embedded into a gel implanted into mice, the cells formed functional human blood vessels. Mice that were suffering from heart damage formed functional human blood vessels in their hearts even interlinking with existing murine vessels to improve heart function.

During the course of the research, the scientists observed increased levels of telomerase the anti-ageing enzyme responsible for telomeres on the ends of chromosome in progenitor cells. The increase in telomerase we see in the progenitor cells could be an added benefit of using this partial de-differentiation technique for the production of new blood vessels for patients with cardiac disease, especially for older patients, said Dr Rehman. The process of converting and expanding these cells in the lab could make them age even further and impair their long-term function. But if the cells have elevated levels of telomerase, the cells are at lower risk of premature ageing.

Increased levels of telomerase are also observed in cancer cells, enabling cell division to occur at avery high rate. However, the scientists didnt observe any tumour formation during their research and their next steps will involve further research over a longer time period in larger animals. The study was published in Circulation.

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Protein enables scientists to convert skin to blood vessels - Lab News

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Get burned over the weekend? RenovaCare has got your back. The New York-based biotech company has expertise in stem cells and organ regeneration, and has brought these skills to bear on wound care. One of the companys most promising methods uses a literal skin gun to spray skin stem cells on a burn or chronic wound to promote rapid healing. The healing is so rapid that you can walk into the hospital with a burn on a Friday night and return on Monday largelyhealed.

The skin gun process uses a patients stem cells, which are collected from healthy skin. The stem cells are isolated from the skin sample and suspended in a water solution that makes them easy to spray. Thecomputer-controlled skin gun works like the air brushes that are used by painters, but with much more precision.

The treatment is stupidly simple just spray the stem cells on the burned skin and wait for them to regrow. It is also extremely fast, taking only 1.5 hours to isolate the cells and and spray the skin. Once the skin cells are applied, it takes only a few days for the treatment to be effective. When state trooper Matthew Uram was burned in an unfortunate bonfire accident, he chose this experimental treatment and was entirely healed from his second-degree burns in four days.

This skin gun approach offers a significant improvement over the current methods of in-lab skin growth and surgical grafting that takes weeks and sometimes even months to be effective. Those who undergo these conventional skin graft techniques often suffer from infections and other setbacks, rendering the treatment far from optimal. A technology like the skin gun that could promote complete healing in a matter of days would represent a clear advance.

RenovaCares skin gun is still in the developmental stage and has not been approved by the FDA for sale in the United States, so you wont be able to find it on the shelves of burn units quite yet. The company is making progress towards that goal, however, and has recently announceda successful round of testing that shows its gun is capable of dispersing the skin cell liquid in a very uniform and dense manner.

Recent experiments conducted at Stem Cell Systems GmbH (Berlin, Germany) show that the gun can spray more than 20,000 evenly distributed droplets in a test area as compared to a conventional needle and syringe which produced only 91. The gun is not only capable of even dispersal, but it also is gentle on the skin stem cells, which retain 97.3 percent viability after SkinGun spraying. RenovaCare is continuing its research and development as it moves towards FDA approval and eventual commercial rollout. The company recently a filed a 510(k) submission with the FDA, which is a notice of intent to market a device and often is the first step before clinical trials.

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New Burn Healing Method uses Skin-Gun Stem-Cell Therapy ...

Jonathan Pitre was exhausted on Tuesday, but he found some strength while watching the Ottawa Senators close out the New York Rangers in Game 6 of their second-round playoff series. -

His white blood cell count rising slowly, Jonathan Pitre will have a medical test Thursday to answer a crucial question: Are the new cells in his bloodstream genetically different?

The answer will reveal whether his second stem cell transplant has taken root in his bone marrow.

I want to be excited but Im holding back until we know for sure, said Pitres mother, Tina Boileau, who has been at his side in Minnesota since the transplant one month ago. Once we know, it seems like well be able to put one foot in front of the other and move on.

The family is taking a cautious approach since Pitres first transplant ended in disappointment in October when doctors learned that his own stem cells had recolonized his bone marrow.

Thursdays test will determine the source of Pitres new cells by isolating his white blood cells and examining the DNA they contain. All of Pitres cells will have a pair of X and Y chromosomes, but doctors will be hoping to find cells with a pair of X chromosomes since those cells can only come from his mother.

Such a discovery would provide evidence that the stem cells donated by Boileau have taken root in her sons bone marrow, and have started to produce new blood cells.

Im really hoping for a positive outcome; I think were due for good news, said Boileau, who expects to learn the results on Monday.

Pitre, who turns 17 next month, has seen his white blood cell count climb recently from 0.0 to 0.4, which remains well below the normal range of 4.0 to 11.0. He continues to suffer fevers, pain and profound exhaustion.

On Tuesday night, he watched the Ottawa Senators close out the New York Rangers while his mother applied fresh dressings and gauze after his bath. It was the first time in his life, Boileau said, that her son did not have the strength to stand during the procedure.

We had the game on and I have to say it really helped us get through it, said Boileau. Jonathan got a bit of strength from the excitement, and it was just enough to help me finish his dressings.

Pitre told his mother Tuesday night that hes not sure if he can see this one through.

I said, Youre going to have to because theres no way Im going home without you,' Boileau said. He managed to crack a little smile and said, OK, mom.

The University of Minnesota Masonic Childrens Hospital is theonly facility in the world that offers a blood and marrow transplant as a treatment for those with severe epidermolysis bullosa (EB). If Pitres transplant is successful, his new stems cells will have the power to deliver to his injured skin cells that can secrete a missing protein essential to the development of collagen.

Collagen is the glue that gives skin its strength and structure, and those with Pitres disease, recessive dytstrophic EB, are missing it. The treatment holds the potential to dramatically improve Pitres skin and make his disease more manageable.

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An exhausted Jonathan Pitre will soon learn if his stem cell transplant has worked - Ottawa Citizen

May 10, 2017 Eye stem cells. Credit: University of Southampton

Reported in Nature today, one of the largest sets of high quality human induced pluripotent stem cell lines from healthy individuals has been produced by a consortium involving the Wellcome Trust Sanger Institute. Comprehensively annotated and available for independent research, the hundreds of stem cell lines are a powerful resource for scientists studying human development and disease.

With collaborative partners from King's College London, the European Bioinformatics Institute, the University of Dundee and the University of Cambridge, the study also investigates in unprecedented detail the extensive variation between stem cells from different healthy people.

Technological advancements have made it possible to take an adult cell and use specific growth conditions to turn back the clock - returning it to an early embryonic state. This results in an induced pluripotent stem cell (iPSC), which can develop into any type of cell in the body. These iPSCs have huge scientific potential for studying the development and the impact of diseases including cancer, Alzheimer's, and heart disease.

However, the process of creating an iPSC is long and complicated and few laboratories have the facilities to characterise their cells in a way that makes them useful for other scientists to use.

The Human Induced Pluripotent Stem Cell Initiative (HipSci) project used standardised methods to generate iPSCs on a large scale to study the differences between healthy people. Reference sets of stem cells were generated from skin biopsies donated by 301 healthy volunteers, creating multiple stem cell lines from each person.

The researchers created 711 cell lines and generated detailed information about their genome, the proteins expressed in them, and the cell biology of each cell line. Lines and data generated by this initiative are available to academic researchers and industry.

Dr Daniel Gaffney, a lead author on the paper, from the Wellcome Trust Sanger Institute, said: "We have created a comprehensive, high quality reference set of human induced pluripotent stem cell lines from healthy volunteers. Each of these stem cell lines has been extensively characterised and made available to the wider research community along with the annotation data. This resource is a stepping stone for researchers to make better cell models of many diseases, because they can study disease risk in many cell types, including those that are normally inaccessible."

By creating more than one stem cell line from each healthy individual, the researchers were able to determine the similarity of stem cell lines from the same person.

Prof Fiona Watt, a lead author on the paper and co-principal investigator of HipSci, from King's College London, said: "Many other efforts to create stem cells focus on rare diseases. In our study, stem cells have been produced from hundreds of healthy volunteers to study common genetic variation. We were able to show similar characteristics of iPS cells from the same person, and revealed that up to 46 per cent of the differences we saw in iPS cells were due to differences between individuals. These data will allow researchers to put disease variations in context with healthy people."

The project, which has taken 4 years to complete, required a multidisciplinary approach with many different collaborators, who specialised in different aspects of creating the cell lines and characterising the data.

Dr Oliver Stegle, a lead author on the paper, from the European Bioinformatics Institute, said: "This study was only possible due to the large scale, systematic production and characterisation of the stem cell lines. To help us to understand the different properties of the cells, we collected extensive data on multiple molecular layers, from the genome of the lines to their cell biology. This type of phenotyping required a whole facility rather than just a single lab, and will provide a huge resource to other scientists. Already, the data being generated have helped to gain a clearer picture of what a typical human iPSC cell looks like."

Dr Michael Dunn, Head of Genetics and Molecular Sciences at Wellcome, said: "This is the fantastic result of many years of work to create a national resource of high quality, well-characterised human induced pluripotent stem cells. This has been a significant achievement made possible by the collaboration of researchers across the country with joint funding provided by Wellcome and the MRC. It will help to provide the knowledge base to underpin a huge amount of future research into the effects of our genes on health and disease. By ensuring this resource is openly available to all, we hope that it will pave the way for many more fascinating discoveries."

Explore further: Stem cell consortium tackles complex genetic diseases

More information: Helena Kilpinen et al, Common genetic variation drives molecular heterogeneity in human iPSCs, Nature (2017). DOI: 10.1038/nature22403

http://www.yourgenome.org/facts/what-is-a-stem-cell

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Scientists unveil the UK's largest resource of human stem cells from healthy donors - Medical Xpress

As we get older, many of us struggle with the harsh reality of our hair turning grey or falling out. But despite how common these problems are, scientists have struggled to identify their underlying biological cause, which means that we've been stuck using quick fixes such as hair dye and toupees to mask the problem.

Now, scientists have finally identified the specific cells that cause hair to grow and develop pigment in mice - a big step towards developing a treatment for grey hair and baldness.

The researchers actually stumbled upon these 'hair progenitor cells' by accident while researching a rare genetic disorder that causes tumours to grow on nerves, called Neurofibromatosis Type 1.

"Although this project was started in an effort to understand how certain kinds of tumours form, we ended up learning why hair turns grey and discovering the identity of the cell that directly gives rise to hair," saidlead researcher Lu Le from the University of Texas Southwestern Medical Centre.

"With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems."

Researchers already knew that skin stem cells contained in the bulge at the bottom of hair follicles were involved in hair growth, but they weren't quite sure what it was made these skin cells turn into hair cells. So they couldn't begin to find a way to target them or stimulate their growth.

But while researching tumour formation on nerve cells, they discovered the protein that sets these cells apart.

Called KROX20, the protein is more commonly associated with nerve development. But in hair follicles in mice the team discovered it switches on in skin cells that will go on to become the hair shaft that makes hair grow.

This protein then causes these cells to produce a protein called stem cell factor (SCF), and when both of these molecules are expressed in a cell, they move up the hair bulb, interact with pigment-producing melanocyte cells, and grow into healthy, coloured hairs.

But if one or the other is missing, the process goes wrong.When the team deleted the KROX20-producing cells, they found that no hair grew and mice became bald.

When they deleted the SCF gene in these hair-progenitor cells, the animal's hair turned white.

To be clear, this research has only been conducted in mice so far. While we have a lot of biological similarities with mice, the study needs to be repeated in humans before we can get too excited.

But Le and his team are already working on a project that will look for KROX20 and SCF in people with greying and thinning hair, in an attempt to work out whether it's associated with male pattern baldness in humans.

The hope is that it might not only teach us about why our hair changes as we get older, but also ageing in general. And the fact that the research could potentially lead to treatments that will help us look younger for longer doesn't hurt either.

The research has been published inGenes & Development.

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Scientists think they've finally found the mechanism behind grey hair and baldness - ScienceAlert

Bone marrow makes our red blood cells

DENNIS KUNKEL MICROSCOPY/SPL

By Helen Thomson

Scientists have engineered a bone-like implant to have its own working marrow that is capable of producing healthy blood. The implant may help treat several blood and immune disorders without the side effects of current treatments.

Bone marrow is the spongy tissue present inside the centre of bones. One of its jobs is to produce red blood cells from stem cells. Bone marrow transplants are sometimes needed to treat immune diseases that attack these stem cells, or in certain types of anaemia, in which the body cant make enough blood cells or clotting factors.

Such transplants involve replacing damaged marrow with bone marrow stem cells from a healthy donor. But first, the recipient must have their own bone marrow stem cells wiped out to make room for the transplanted donor cells. This is done using radiation and drugs, which can have serious side effects, such as nausea and loss of fertility.

To get round this problem, Shyni Varghese at the University of California, San Diego, and her colleagues have engineered an implant that resembles real bone. It provides a home for donor cells to grow and proliferate, bypassing the need for any drug and radiation treatment.

The implant has two main sections: an outer bone-like structure and an inner marrow, both engineered from a hydrogel matrix. Within the outer structure, calcium phosphate minerals help stem cells from the host grow into cells that help build bone. The inner matrix creates a home for donor bone marrow stem cells.

When placed beneath the skin in mice, the implant grew into a bone-like structure and produced a working marrow. Blood cells made by the donor stem cells inside the implant were able to get into circulation where they mixed with the hosts own blood cells. Six months later, blood cells from both the donor and host were still circulating around the body.

Its an additional accessory for the host, says Varghese. They have their own bone tissue and now an additional one that can be used if needed. Its like having more batteries for the bone.

Since the implant contributes to the hosts blood supply, rather than replacing it altogether, it cannot be used to treat people who have blood cancers, who would still need to have their own bone marrow stem cells wiped out to cure the disease.

Edward Gordon-Smith, emeritus professor of haemotology at St Georges University of London, says that the study isa splendid achievement.He says the structure could also offer a new way of studying blood stem cells and how blood disorders arise.

Journal reference: PNAS, DOI: 10.1073/pnas.1702576114

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Synthetic bone implant can make blood cells in its marrow - New Scientist

The newtechnique involves isolating and spraying the patient's own skin stem cells on the burn wounds

BURNS victims are being treated with an amazing gun which sprays them with stem cells and makes skin rapidly grow.

Treatment for people with extensive burns is a painful process and can often take weeks or months as surgeons take large sheets of skin from elsewhere on the body and graft it onto the affected area with the prospect of permanent scars a possibility.

Renova Care

Renova Care

Doctors in the US have developed the SkinGun, anew technique which involves isolating and spraying the patients own skin stem cells on the burn wounds.

Response to the SkinGun has been positive with patients saying their new skin is virtually indistinguishable from the rest of their body, the Daily Mail has reported.

Thomas Bold, chief executive of RenovaCare, the company behind SkinGun, said: The procedure is gentler and the skin that regrows looks, feels and functions like the original skin.

The procedure involves a small patch of healthy skin being removed.

Then stem cells are separated out and placed in a solution which is then sprayed onto the wound.

The whole thing takes around 90 minutes.

Case studies include a 43-year-old man who suffered serious burns to his upper left arm, shoulder, back and torso after he was scalded by hot water and left him with huge welts.

Within six days new skin had formed over the wound and he was discharged from hospital.

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Burn victims treated with amazing gun which sprays them with stem cells and makes skin grow - The Sun

Skin cells found at root of balding, gray hair Science Daily The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell ...

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Skin cells found at root of balding, gray hair - Science Daily

Ive been a fan of stem cells ever since I discovered ReLuma and AQ Skin Solutions, both of which use human conditioned media from adult adipose fat. Back then, it was a leap of face based on research surrounding stem cells and wound healing. Ever since, I have relied on my own experience and reports from the Truth In Aging community stem cells seem to work. So, I was excited (and vindicated) to read new research on stem cells and aging.

Researchers from the Perelman School of Medicine at the University of Pennsylvania found adult stem cells collected from human fat have a potential use to treat aging. Their findings are published in the journal, Stem Cells. The posh name for fat is adipose (worth keeping in mind if you want to bewilder a loved one by asking them if your bottom looks adipose in these pants). Anyway, adipose-derived stem cells (ASCs), create more proteins than researchers initially thought even when harvested from the elderly.

Our study shows these cells are very robust, even when they are collected from older patients, said Ivona Percec, M.D., director of Basic Science Research in the Center for Human Appearance and the study's lead author. It also shows these cells can be potentially used safely in the future because they require minimal manipulation and maintenance. Now, notice Dr. Percec uses the word safely. This is also a useful development, because we have never really known whether administering stem cells as anti-agers was really a safe thing to do.

Interestingly, adipose stem cells behave differently to other stem cells such as fibroblasts from the skin in that they are more stable over time and the rate at which they multiply stays consistent even as we age. I found some research from 2013 that speculated that these cells may be the same in infants through to the elderly. Dr. Perecs research seems to have clinched that this is indeed the case.

When you harvest adipose derived stem cells, they can become virtually any type of cell and put to the service of anti-aging, as well as healing purposes. Recent research has shown that they are a powerful source of skin regeneration because of their capability to provide not just cells but also tons of cytokines, or growth factors. The result, as one research paper puts it, is great promise for applications in repair of skin, rejuvenation of aging skin and aging-related skin lesions.

Adipose stem cells were discovered 40 years after the identification of bone marrow stem cells, opening up a new era of active stem cell therapy. It looks as if we are on the threshold of much more discovery in this field. For instance, Dr. Percec and her team are taking the research a step further to look at how tight the DNA is wound around proteins inside the cells and the way this affects aging.

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New Study Finds Human Fat Has Potential to Treat Aging - Truth In ... - Truth In Aging

Science Daily

Scientists turn human induced pluripotent stem cells into lung cells Science Daily CReM scientists work with induced pluripotent stem cells, or iPSCs, which were discovered by Shinya Yamanaka in 2006. Yamanaka figured out how to take an adult cell in the human body -- like a blood cell or skin cell -- and "reprogram" it into a stem ... and more »

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Scientists turn human induced pluripotent stem cells into lung cells - Science Daily

Researchers have modified mouse stem cells to combat the kind of inflammation that arthritis and other conditions cause. The stem cells may one day be used in a vaccine that would fight arthritis and other chronic inflammation conditions in humans, a new paper suggests.

Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy), develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation.

Researchers initially worked with skin cells from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation. The research is availablein the journal Stem Cell Reports.

Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed, says Farshid Guilak, the papers senior author and a professor of orthopedic surgery at Washington University School of Medicine. To do this, we needed to create a smart cell.

Many current drugs used to treat arthritisincluding Enbrel, Humira, and Remicadeattack an inflammation-promoting molecule called tumor necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, says Guilak, also a professor of developmental biology and of biomedical engineering and codirector of Washington Universitys Center of Regenerative Medicine.

If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.

As part of the study, Guilak and his colleagues grew mouse stem cells in a test tube and then used CRISPR technology to replace a critical mediator of inflammation with a TNF-alpha inhibitor.

We hijacked an inflammatory pathway to create cells that produced a protective drug.

Exploiting tools from synthetic biology, we found we could re-code the program that stem cells use to orchestrate their response to inflammation, says Jonathan Brunger, the papers first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

Over the course of a few days, the team directed the modified stem cells to grow into cartilage cells and produce cartilage tissue. Further experiments by the team showed that the engineered cartilage was protected from inflammation.

We hijacked an inflammatory pathway to create cells that produced a protective drug, Brunger says.

The researchers also encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists easily could determine when the cells were responding. Recently, Guilaks team has begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drugthe TNF-alpha inhibitorthat would protect the synthetic cartilage cells that Guilaks team created and the natural cartilage cells in specific joints.

When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation, Guilak explains. We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, its possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.

With an eye toward further applications of this approach, Brunger adds, The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health supported this work. The Nancy Taylor Foundation for Chronic Diseases; the Arthritis Foundation; the National Science Foundation; and the Collaborative Research Center of the AO Foundation in Davos, Switzerland, provided additional funding.

Authors Farshid Guilak and Vincent Willard have a financial interest in Cytex Therapeutics of Durham, North Carolina, which may choose to license this technology. Cytex is a startup founded by some of the investigators. They could realize financial gain if the technology eventually is approved for clinical use.

Source: Washington University at St. Louis

Link:
How 'smart' stem cells could lead to arthritis vaccine - Futurity: Research News

An artist's impression of a reprogrammed stem cell.

Ella Marushchenko

In a curious confluence of the information technology industrys favourite word and scientists weakness for punning acronyms, researchers in St Louis, Missouri, in the US, have created what have been dubbed SMART cells.

SMART, in this case, stands for Stem cells Modified for Autonomous Regenerative Therapy, and their creation by a team based jointly at the Washington University School of Medicine and Shriners Hospital for Children promises a novel treatment for arthritis and other chronic conditions.

The team, led by Washington Universitys Farshid Guilak, reasoned that much of the pain and discomfort endured by arthritis suffers arises from inflammation caused by damaged cartilage. Reducing that inflammation, therefore, is an important therapeutic outcome.

To test this the team used mice. First, they harvested skin cells from tails, then turned them into stem cells. Next, using CRISPR gene-editing technology they excised a gene associated with inducing inflammation and replaced it with one that dampens it.

The resulting cells were then induced to grow into cartilage cells in cultures. The tissue thus produced was found to be free of inflammation.

In a clever move perhaps making the stem cells doubly smart Guilak and his colleagues further modified the stem cells so that they would light up when experiencing inflammation, making them easy to spot.

The research is published in in the journal Stem Cell Reports, and includes the news that research has now commenced using live mice.

Should the SMART cells eventually be found to be a viable avenue for human treatment, the results promise to be both more effective and better focused than existing arthritis drugs.

Pharmacological approaches to arthritis treatment mainly target the inflammation-promoting molecule called tumor necrosis factor alpha. The problem, however, is that they all do so on a system-wide basis, weakening the immune system and making patients more liable to infection.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localised inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, says Guilak.

Study co-author Jonathan Brunger says the most pleasing aspect of the teams CRISPR-based approach is that it effectively highjacks the inflammatory pathway and turns it into a protective mechanism.

The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine, he adds.

Link:
SMART cells to fight arthritis - Cosmos