Researchers regrow human corneas in mice

Kurzweil AI - Mon, 07/07/2014 - 6:51am

A restored functional cornea following transplantation of human ABCB5-positive limbal stem cells to limbal stem cell-deficient mice (credit: Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank)

A team of Boston medical researchers has identified a way to trigger regrowth of human corneal tissue using stem cells. The finding could restore vision for victims of chemical injury and others with damaging eye diseases.

The corneal limbus, a source of stem cells, is the border of the cornea and the sclera (the white of the eye) (credit: Wikimedia Commons)

Limbal stem cells, which reside in the eye’s limbus, help maintain and regenerate corneal tissue. Their loss due to injury or disease is one of the leading causes of blindness.

In the past, tissue or cell transplants have been used to help the cornea regenerate, but it was unknown whether there were actual limbal stem cells in the grafts, or how many, and the outcomes were not consistent.

A marker for limbal stem cells

In this new study, researchers at the Massachusetts Eye and Ear/Schepens Eye Research Institute (Mass. Eye and Ear), Boston Children’s Hospital, Brigham and Women’s Hospital, and the VA Boston Healthcare System used a molecule known as ABCB5, which acts as a marker for hard-to-find limbal stem cells.

ABCB5 allowed the researchers to locate hard-to-find limbal stem cells in tissue from deceased human donors and use these stem cells to regrow anatomically correct, fully functional human corneas in mice.

“Limbal stem cells are very rare, and successful transplants are dependent on these rare cells,” says Bruce Ksander, Ph.D., of Mass. Eye and Ear, co-lead author on the study with post-doctoral fellow Paraskevi Kolovou, M.D. “This finding will now make it much easier to restore the corneal surface. It’s a very good example of basic research moving quickly to a translational application.”

Composite image depicting the palisades of Vogt within the human limbus (left), ABCB5-positive limbal stem cells isolated from the palisades (right; ABCB5 — green, nucleus — red) and a restored functional cornea following transplantation of human ABCB5-positive limbal stem cells to limbal stem cell-deficient mice (bottom right) (credit: Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank)

The research, published in Nature, is also one of the first known examples of constructing a tissue from an adult-derived human stem cell, the researchers say.

The discovery

ABCB5 was originally discovered in the lab of Markus Frank, M.D., of Boston Children’s Hospital, and Natasha Frank, M.D., of the VA Boston Healthcare System and Brigham and Women’s Hospital (co-senior investigators on the study) as being produced in tissue precursor cells in human skin and intestine.

In the new work, using a mouse model developed by the Frank lab, they found that ABCB5 also occurs in limbal stem cells and is required for their maintenance and survival, and for corneal development and repair. Mice lacking a functional ABCB5 gene lost their populations of limbal stem cells, and their corneas healed poorly after injury.

“ABCB5 allows limbal stem cells to survive, protecting them from apoptosis [programmed cell death],” says Markus Frank. “The mouse model allowed us for the first time to understand the role of ABCB5 in normal development, and should be very important to the stem cell field in general.” according to Natasha Frank.

Markus Frank is working with the biopharmaceutical industry to develop a clinical-grade ABCB5 antibody that would meet U.S. regulatory approvals.

“A single lab cannot do a study like this,” says Natasha Frank, also affiliated with the Harvard Stem Cell Institute. “It integrates genetics, knockout mice, antibodies, transplantation—a lot of technical expertise that we were lucky came together in a very nice way.

Human trials planned

“Our study demonstrated that the cell surface protein ABCB5 is essential for normal limbal stem cell function in corneal development and repair, through critical roles in stem cell maintenance and survival,” she explained to KurzweilAI in an email. “Furthermore, our findings show that the capacity to fully restore the cornea is exclusively contained within the ABCB5-positive limbal stem cell compartment (human or mouse), indicating that this pure limbal stem cell population has the potential to significantly improve therapy for corneal disease associated with limbal stem cell deficiency.

“Until now, no molecular marker existed for limbal stem cells by which these rare cells could be isolated and purified. Previously published work on limbal epithelial cell grafts showed that when more than three percent of transplanted cells were stem cells, transplants were successful — less than three percent and the transplants were not. We hypothesized that ABCB5 would represent a marker for limbal stem cells, based on its expression on stem and progenitor cell populations in other human tissues.

“While we tested the capacity of human limbal stem cells to regenerate the cornea upon grafting to limbal stem cell-deficient mice, we would expect this novel transplant approach to also work in humans, and efforts are currently underway to meet regulatory requirements to allow testing in human clinical trials.

“More research to develop the technique and make sure it is safe will be required before human trials can take place, and we expect this to take one to two years before entering clinical trials, with several additional years of clinical study needed before the treatment might become ultimately available.”

The research was supported by the National Institute of Neurological Disorders and Stroke (grant K08NS051349), the Veterans Administration (BLR&D 1I01BX000516 and VA RR&D 1I01RX000989), the Harvard Stem Cell Institute, the National Cancer Institute (R01CA113796, R01CA158467, R01CA138231), the Department of Defense (PR0332453), the National Institutes of Health (R01EY018624, P30EY014801, R01EY021768, R01CA138231, R01EB017274, U01HL100402, P41EB015903 and NIH New Innovator Award DP2OD007483), the Corley Research Foundation, the Western Pennsylvania Medical Eye Bank Core Grant for Vision Research (EY08098), the Howard Hughes Medical Institute and the Life Sciences Research Foundation.

Abstract of Nature paper

Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far. Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5) marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated human or murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC-deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs in mice and p63α-positive LSCs in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.

Categories: Science

Free Wi-Fi Supplier, Gowex, Files For Bankruptcy

Slashdot - Mon, 07/07/2014 - 6:00am
PuceBaboon writes "The BBC is reporting that a Spanish firm, Gowex, which provides free Wi-Fi services in major cities world-wide, has filed for bankruptcy, following revelations that financial accounts filed over the past four years were "false". The company supplies services in London, Shanghai, New York and Buenos Aires, as well as Madrid. Other sources report that up to 90% of the company's reported revenue came from "undisclosed related parties" (in other words, from Gowex itself) and that the value of the company's share price was now effectively zero.

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Categories: Science

Police Using Dogs To Sniff Out Computer Memory

Slashdot - Mon, 07/07/2014 - 3:06am
First time accepted submitter FriendlySolipsist points out a story about Rhode Island Police using a dog to find hidden hard drives. The recent arrival of golden Labrador Thoreau makes Rhode Island the second state in the nation to have a police dog trained to sniff out hard drives, thumb drives and other technological gadgets that could contain child pornography. Thoreau received 22 weeks of training in how to detect devices in exchange for food at the Connecticut State Police Training Academy. Given to the state police by the Connecticut State Police, the dog assisted in its first search warrant in June pinpointing a thumb drive containing child pornography hidden four layers deep in a tin box inside a metal cabinet. That discovery led the police to secure an arrest warrant, Yelle says. “If it has a memory card, he’ll sniff it out,” Detective Adam Houston, Thoreau’s handler, says.

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Categories: Science

FDA: We Can't Scale To Regulate Mobile Health Apps

Slashdot - Mon, 07/07/2014 - 12:40am
chicksdaddy writes Mobile health and wellness is one of the fastest growing categories of mobile apps. Already, apps exist that measure your blood pressure and take your pulse, jobs traditionally done by tried and true instruments like blood pressure cuffs and stethoscopes. If that sounds to you like the kind of thing the FDA should be vetting, don't hold your breath. A senior advisor to the U.S. Food and Drug Administration (FDA) has warned that the current process for approving medical devices couldn't possibly meet the challenge of policing mobile health and wellness apps and that, in most cases, the agency won't even try. Bakul Patel, and advisor to the FDA, said the Agency couldn't scale to police hundreds of new health and wellness apps released each month to online marketplaces like the iTunes AppStore and Google Play.

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Categories: Science

No Shortage In Tech Workers, Advocacy Groups Say

Slashdot - Sun, 06/07/2014 - 11:33pm
sabri writes To have a labor shortage or not to have, that's the question. According to the San Jose Mercury News: Last month, three tech advocacy groups launched a labor boycott against Infosys, IBM and the global staffing and consulting company ManpowerGroup, citing a "pattern of excluding U.S. workers from job openings on U.S soil." They say Manpower, for example, last year posted U.S. job openings in India but not in the United States." "It's getting pretty frustrating when you can't compete on salary for a skilled job," said Rich Hajinlian, a veteran computer programmer from the Boston area. "You hear references all the time that these big companies ... can't find skilled workers. I am a skilled worker."

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Categories: Science

Oculus Suspends Oculus Rift Dev Kit Sales In China

Slashdot - Sun, 06/07/2014 - 10:30pm
An anonymous reader writes with news about how Oculus is dealing with the reselling of dev kits in China. Bad news for those of you looking to get your hands on a preorder of the Oculus Rift virtual reality headset. A representative from Oculus recently confirmed that the company has had to stop selling its headsets in China as a result of an undisclosed amount of reselling. Which is to say, some of those preordering the developer edition of the virtual reality headset in China — not the consumer product, which hasn't been officially released in any capacity just yet — aren't actually looking to develop anything on the headsets. Nor are they even interested in getting a first look at the virtual reality capabilities of the $350 development kit. They're scalping, plain and simple, to take advantage of what appears to be a hefty amount of demand for the device.

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Categories: Science

Cassini's Space Odyssey To Saturn

Slashdot - Sun, 06/07/2014 - 9:23pm
An anonymous reader writes in with this look at the amazingly successful Cassini mission and the discoveries it has made. Scientists says Cassini is helping them understand how our solar system developed. Of the astronomically profound discoveries it's made over a decade of circling, the startling hint this April of a new moon being formed in the rings of Saturn is merely the latest. Indeed, the spacecraft Cassini — which inserted itself into orbit around the giant gas planet in July, 2004 — has transmitted imagery and sensory data back to Earth that has given us a new understanding of our bejewelled neighbour three doors down. "It's one of the most successful (space) missions probably ever," says University of Toronto astrophysicist Hanno Rein, whose own work has been significantly informed by the tiny craft's output.

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Categories: Science

Comet Pan-STARRS marches across the sky

Science Daily - Sun, 06/07/2014 - 9:18pm
NASA's NEOWISE mission captured a series of pictures of comet C/2012 K1 -- also known as comet Pan-STARRS -- as it swept across our skies in May 2014. The comet is named after the astronomical survey project called the Panoramic Survey Telescope and Rapid Response System in Hawaii, which discovered the icy visitor in May 2012.
Categories: Science

Consciousness On-Off Switch Discovered Deep In Brain

Slashdot - Sun, 06/07/2014 - 8:16pm
An anonymous reader writes "One moment you're conscious, the next you're not. For the first time, researchers have switched off consciousness by electrically stimulating a single brain area. Although only tested in one person, the discovery suggests that a single area – the claustrum – might be integral to combining disparate brain activity into a seamless package of thoughts, sensations and emotions. It takes us a step closer to answering a problem that has confounded scientists and philosophers for millennia – namely how our conscious awareness arises. When the team zapped the area with high frequency electrical impulses, the woman lost consciousness. She stopped reading and stared blankly into space, she didn't respond to auditory or visual commands and her breathing slowed. As soon as the stimulation stopped, she immediately regained consciousness with no memory of the event. The same thing happened every time the area was stimulated during two days of experiments.

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Categories: Science

Rewriting the history of volcanic forcing during the past 2,000 years

Science Daily - Sun, 06/07/2014 - 7:33pm
Scientists have completed the most accurate and precise reconstruction to date of historic volcanic sulfate emissions in the Southern Hemisphere. The new record is derived from a large number of individual ice cores collected at locations across Antarctica and is the first annually resolved record extending through the Common Era.
Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

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Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science

A Tour of One of the World's Only Underwater Labs With Fabien Cousteau

Slashdot - Sun, 06/07/2014 - 7:10pm
An anonymous reader writes Having completed his 31-day stretch underwater, Fabien Cousteau, grandson of famed oceanographer Jacques Cousteau, shows off his underwater laboratory to PBS in this video. When asked about his observations' Fabien said' "It's just amazing, we've seen so much new behavior that I've never seen before. Fish sleeping in sponges, a goliath grouper attacking a barracuda, never seen that before, I don't think anyone has ever caught it on film before. Christmas tree worms, spawning and giving off this milky smoke like stuff off. I mean it's just science fiction, it's really amazing down here. And that's why we're down here, my grandfather used to say, in order to film a fish you must become a fish. So we're trying to get as close as we can to becoming fish."

Read more of this story at Slashdot.








Categories: Science