Stem Cell Clinic

Embattled Stem Cell Researchers Sue Harvard And Brigham And Women's Hospital

By Stem Cell Medicine

Two embattled and highly controversial stem cell researchers are suing the Brigham and Womens Hospital and Harvard Medical School for an ongoing investigation into their research. The investigation has already resulted in the retraction of one paper inCirculationand anexpression of concern about another paper in theLancet.

The suit was filed by Piero Anversa, the highly prominent stem cell researcher who is a Harvard professor and the head of a large lab at the Brigham, and his longtime colleague,Annarosa Leri, an associate professor of medicine at Harvard who has coauthored many papers with Anversa. The suit places the blame for any scientific misconduct relating to the two papers on a third colleague and coauthor,Jan Kajstura, their longtime collaborator. In an explanation of the problems relating to the Circulation paper,Anversa and Leri accuse Kajstura of doctoring data in a spreadsheet in such a way that they could not have detected it. For theLancet paper the two scientists say thatKajstura and another unnamed scientist in the lab altered two images. Kastura is no longer at the Brigham.

The news was first reported byCarolyn Johnson in theBoston GlobeandJessica Bartlett in the Boston Business Journal. The story has also been reported in depth by Ivan Oransky onRetraction Watch.

The lawsuit accuses Elizabeth Nabel, the president of the Brigham, and the individual members of the investigating panel, of inappropriate and illegal behavior and conflicts of interest.At one point the complaint alleges that the scientists on the panel lack substantial expertise in the relevant scientific areas, including cardiac stem cells. But then, when another member was added to the panel, Ulrich von Andrian, the complaint states that he suffers from serious conflicts of interest that impede his ability to participate in the investigation in an impartial manner. Nabel and von Andrian, along with other Harvard and Brigham figures, serve on the scientific advisory board of Moderna Therapeutics, a stem cell company pursuing an alternative modality for regenerative treatment of cardiac disease.

Anversa and Leri further allege that the investigation caused the withdrawal of a multimillion dollar offer to purchase their company, Autologous/Progenital. The investigation also ended efforts to recruit Anversa and Leri to the University of Miami and the Mt. Sinai School of Medicine in New York.

The complaint discloses that as a result of the ongoing investigation Anversa and Leri were subject to embarrassing questions from other prominent stem cell researchers, including Joshua Hare, Steven Houser, and Eduardo Marban. These researchers, the complaint states, had no need to know of the inquiry.

Anversa and Leri also criticizethe panel for expanding its investigation to at least 15 papers from the research group. There is no justification for expanding the investigation to encompass these additional papers at this late stage. Most were published before the inquiry process began in January 2013, and all were published before the investigation began in February 2014. It is unclear from the complaint why these papers should not have been subject to scrutiny.

As I reported in 2011, the Lancet paper reporting the results of theSCIPIO trial was the subject of considerable hype at the time of its original publication. ABC News, CBS News and other media outlets used phrases like medical breakthrough and heart failure cure. ABC News correspondent Richard Besser was so enthusiastic that anchor Diane Sawyer commented that she had never seen him so excited. The first author of SCIPIO, Roberto Bolli, said the work could represent the biggest advance in cardiology in my lifetime.

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Embattled Stem Cell Researchers Sue Harvard And Brigham And Women's Hospital

365 days: 2014 in science

By Stem Cell Clinic

Keith Vanderlinde/NSF

The BICEP2 telescope at the South Pole may have spied gravitational waves or dust.

This year may be best remembered for how quickly scientific triumph morphed into disappointment, and even tragedy: breakthroughs in stem-cell research and cosmology were quickly discredited; commercial spaceflight faced major setbacks. Yet landing a probe on a comet, tracing humanitys origins and a concerted push to understand the brain provided reasons to celebrate.

Asian nations soared into space this year. The Indian Space Research Organisation put a mission into orbit around Mars the first agency to do so on its first try. Japan launched the Hayabusa-2 probe, its second robotic voyage to bring back samples from an asteroid. And even as Chinas lunar rover Yutu (or Jade Rabbit) stopped gathering data on the Moons surface, mission controllers took the next step in the countrys lunar exploration programme by sending a test probe around the Moon and back to Earth.

But for commercial spaceflight, it was a bad year. Virgin Galactics proposed tourism vehicle SpaceShipTwo disintegrated during a test flight in California and killed one of its pilots. That came just three days after a launch-pad explosion in Virginia destroyed an uncrewed private rocket intended to take supplies to the International Space Station. The accident wiped out a number of research experiments destined for the station, whose managers are trying to step up its scientific output. Problems on the station also delayed the deployment of a flock of tiny Earth-watching satellites, nicknamed Doves, which are part of the general trend of using miniature CubeSats to collect space data.

On a bigger scale, the European Space Agency successfully launched the first in its long-awaited series of Sentinel Earth-observing satellites.

After a decade-long trip, the European Space Agencys Rosetta spacecraft arrived at comet 67P/ChuryumovGerasimenko in August and settled into orbit. Three months later, Rosetta dropped the Philae probe to 67Ps surface, in the first-ever landing on a comet. Philae relayed science data for 64hours before losing power in its shadowy, rocky landing site.

Meanwhile, a flotilla of Mars spacecraft probes from India, the United States and Europe had an unplanned close brush with comet Siding Spring, which zipped past the red planet in October at a distance of 139,500kilometres about one-third of the distance from Earth to the Moon. NASA rovers continued to trundle along on the Martian surface: Curiosity finally reached the mountain that it has been heading towards since landing in 2012, and Opportunity passed 40kilometres on its odometer, breaking a Soviet lunar rovers distance record for off-Earth driving.

The search for planets beyond the Solar System also got a huge boost. In February, the team behind the now mostly defunct Kepler spacecraft announced that it had confirmed the existence of 715extrasolar planets, the largest-ever single haul. Kepler data also revealed the first known Earth-sized exoplanet in the habitable zone of its star, a step closer to the long-sought Earth twin.

Considering that they have been dead for around 30,000 years, Neanderthals had a hell of a year. Their DNA survives in non-African human genomes, thanks to ancient interbreeding, and two teams this year catalogued humans Neanderthal heritage. Scientists learnt more about the sexual encounters between Homo neanderthalensis and early humans after analysing the two oldest Homo sapiens genomes on record from men who lived in southwest Siberia 45,000years ago and in western Russia more than 36,000years ago, respectively. The DNA revealed hitherto-unknown human groups and more precise dates for when H.sapiens coupled with Neanderthals, which probably occurred in the Middle East between 50,000 and 60,000 years ago. Radiocarbon dating of dozens of archaeological sites in Europe, meanwhile, showed that humans and Neanderthals coexisted there for much longer than was once thought up to several thousand years in some places.

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365 days: 2014 in science

Stem cells faulty in Duchenne muscular dystrophy, Stanford researchers find

By Stem Cell Clinic

PUBLIC RELEASE DATE:

17-Dec-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center @sumedicine

Like human patients, mice with a form of Duchenne muscular dystrophy undergo progressive muscle degeneration and accumulate connective tissue as they age. Now, researchers at the Stanford University School of Medicine have found that the fault may lie at least partly in the stem cells that surround the muscle fibers.

They've found that during the course of the disease, the stem cells become less able to make new muscle and instead begin to express genes involved in the formation of connective tissue. Excess connective tissue -- a condition called fibrosis -- can accumulate in many organs, including the lungs, liver and heart, in many different disorders. In the skeletal muscles of people with muscular dystrophy, the fibrotic tissue impairs the function of the muscle fibers and leads to increasing weakness and stiffness, which are hallmarks of the disease.

The researchers discovered that this abnormal change in stem cells could be inhibited in laboratory mice by giving the animals a drug that is already approved for use in humans. The drug works by blocking a signaling pathway involved in the development of fibrosis. Although much more research is needed, the scientists are hopeful that a similar approach may one day work in children with muscular dystrophy.

"These cells are losing their ability to produce muscle, and are beginning to look more like fibroblasts, which secrete connective tissue," said Thomas Rando, MD, PhD, professor of neurology and neurological sciences. "It's possible that if we could prevent this transition in the muscle stem cells, we could slow or ameliorate the fibrosis seen in muscular dystrophy in humans."

A paper describing the researchers' findings will be published Dec. 17 in Science Translational Medicine. Rando, the paper's senior author, is director of the Glenn Laboratories for the Biology of Aging and founding director of the Muscular Dystrophy Association Clinic at Stanford. Former postdoctoral scholar Stefano Biressi, PhD, is the lead author. Biressi is now at the Centre for Integrative Biology at the University of Trento in Italy.

A devastating disease

Duchenne muscular dystrophy is a devastating disease that affects about 1 in every 3,600 boys born in the United States. Patients usually experience severe, progressive muscle weakness that confines them to a wheelchair in early adolescence and eventually leads to paralysis. It's caused by mutations in the dystrophin gene, which encodes the dystrophin protein. The dystrophin protein serves to connect muscle fibers to the surrounding external matrix. This connection stabilizes the fibers, enhancing their strength and preventing injury. Sufferers are nearly always boys because the dystrophin gene is located on the X chromosome. (Girls would need to inherit two faulty copies, which is unlikely because male carriers often die in early adulthood.)

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Stem cells faulty in Duchenne muscular dystrophy, Stanford researchers find

Press Conference for Researcher Accused of Fraud Becomes TV Phenomenon in Japan

By Stem Cell Doctors

TOKYO Live broadcasts of scientist Haruko Obokata's press conference, in which she defended her groundbreaking stem cell research against allegations of data fabrication, were a ratings hit on multiple TV networks and online platforms on Wednesday.

The event in a hotel in Osaka attracted 300 members of the domestic and international media, and was broadcast live on most of Japan's major networks. Nihon Terebi (NTV) topped the ratings with 12.3 percent, with public broadcaster NHK in second with 9.4 percent and Tokyo Broadcasting Systems (TBS) in third with 6.8 percent, according to Video Research Inc.

GALLERY: Bollywood's Blatant Copies of Hollywood Movie Posters

The press conference was scheduled to run for 30 minutes, but ended up lasting more than two hours, as Obokata, age 30, sometimes struggled to answer questions from hostile members of the media. TV networks extended news programs and shifted schedules to continue coverage.

TV Tokyo, famous for ignoring major news events and sticking with its regular schedule, went ahead with an episode of Law & Order, followed by straight-to-video Canadian action movie Recoil.

The Wednesday lunchtime event attracted more than 1.26 million to a live Ustream broadcast and 550,000 viewers to a live stream on Nico Nico Douga, a Japanese online video platform that allows users to post comments on-screen in real time. More than 690,000 comments were posted during the course of the press conference.

Around 112,500 Tweets relating to the events at the press conference were sent in two hours.

STORY: Japan's Fuji TV Links With Crunchyroll to Stream Dramas in the U.S.

Obokata, who had been hailed as a pioneer in Japan's male-dominated scientific world, was hospitalized on Monday suffering from stress, and faced the media against the advice of doctors.

In January, Obokata was hailed as a scientific star in the local media after what appeared to be groundbreaking stem cell research by a team she led was published in British scientific journal Nature. Stories about the researcher, who spent two years at Harvard, focused on her cute apron worn in place of a traditional lab coat, and how she had persevered in the face of adversity.

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Press Conference for Researcher Accused of Fraud Becomes TV Phenomenon in Japan

Four clinics face action over stem-cell treatment claims

By Stem Cell Treatment

The wife of well-known former monk Mitsuo Shibahashi, previously known as Phra Mitsuo Gavesako, owns one of the clinics. The department began looking into their operation after one patient complained about losing more than Bt2 million on the treatment. The patient was treated for and hopes to recover from a brain infarction (stroke or blood clot).

Probes reveal the clinics allegedly provided basic check-ups before arranging for their customers to get stem-cell injections in Germany. "According to the Medical Council's regulations, stem-cell treatment is allowed for blood-related diseases only," the department's director-general Boonruang Triruangwor-awat said yesterday.

He said three of the four clinics had clearly violated rules about advertising medical services. "[Their] benefits are exaggerated," he said,

The four clinics are located in CentralWorld, Ekkamai area, Soi Thonglor 55, and Ploenchit Centre.

Boonruang said these clinics could be punished under Article 34(2) of the Medical Facilities Act.

"Offenders face a jail term of up to one year or a maximum fine of Bt20,000," he said.

He added that his department was also in the process of seeking the Medical Council's ruling to determine if these clinics could be punished under Article 49.

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Four clinics face action over stem-cell treatment claims

University of Toronto cell biologists discover on-off switch for key stem cell gene – Discovery may propel advances in …

By Stem Cell Medicine

TORONTO, ON Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animals genome the controller directs when a particular gene the pilot can perform its prescribed function.

A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal.

We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells, said Professor Jennifer Mitchell of U of Ts Department of Cell and Systems Biology, lead investigator of a study published in the December 15 issue of Genes & Development.

Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR, said Mitchell.

Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome made some people more likely to develop certain diseases. They have found that the answers are more often in the regions of the human genome that turn genes on and off.

If we want to understand how genes are turned on and off, we need to know where the sequences that perform this function are located in the genome, said Mitchell. The parts of the human genome linked to complex diseases such as heart disease, cancer and neurological disorders can often be far away from the genes they regulate, so it can be difficult to figure out which gene is being affected and ultimately causing the disease.

It was previously thought that regions much closer to the Sox2 gene were the ones that turned it on in embryonic stem cells. Mitchell and her colleagues eliminated this possibility when they deleted these nearby regions in the genome of mice and found there was no impact on the genes ability to be turned on in embryonic stem cells.

We then focused on the region weve since named the SCR as my work had shown that it can contact the Sox2 gene from its location 100,000 base pairs away, said study lead author Harry Zhou, a former graduate student in Mitchells lab, now a student at U of Ts Faculty of Medicine. To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells. Once we had a good idea that this region could be acting on the Sox2 gene, we removed the region from the genome and monitored the effect on Sox2.

The researchers discovered that this region is required to both turn Sox2 on, and for the embryonic stem cells to maintain their characteristic appearance and ability to differentiate into all the cell types of the adult organism.

Just as deletion of the Sox2 gene causes the very early embryo to die, it is likely that an abnormality in the regulatory region would also cause early embryonic death before any of the organs have even formed, said Mitchell. It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells.

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University of Toronto cell biologists discover on-off switch for key stem cell gene - Discovery may propel advances in ...

Cutting Out the Cellular Middleman: New Technology Directly Reprograms Skin Fibroblasts For a New Role

By Uncategorized

PHILADELPHIA As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei George Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

The research was supported by the National Institutes of Health (R01-AR054593, P30-AR057217)

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Cutting Out the Cellular Middleman: New Technology Directly Reprograms Skin Fibroblasts For a New Role

New technology directly reprograms skin fibroblasts for a new role

By Uncategorized

As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei "George" Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

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New technology directly reprograms skin fibroblasts for a new role

New Procedure Gives Tulsan A Chance To Walk Using His Own Stem Cells

By Stem Cell Treatment

TULSA, Oklahoma -

It's a procedure that saved a Tulsa man from having knee surgery and his doctor says it's a revolution in medical care.

Doctors used Michael Conte's own stem cells to heal his damaged knee in a treatment that's only recently become available in Oklahoma.

To Michael Conte, breathing underwater is as much a part of his life as breathing fresh air. After all, he and his wife, both scuba instructors at Oral Roberts University were married under the sea in the Bahamas in 1992.

He works several jobs, is in the National Guard, mountain bikes, weight trains and walks. Michael is as active as a 49-year-old man as you'll find anywhere.

"I work at American, I'm in the military, I teach at ORU, I'm always on the go," said Michael Conte.

After a recent knee injury, you can imagine the disappointment when his doctor told Michael, he would have to slow down because he needed a knee replacement. So Michael started looking for other options.

"I'm definitely too I mean young to have a knee replacement. And they're only good for like ten years. So it doesn't really solve anything," said Michael Conte.

What he found was stem cell treatment and Dr. Venkatesh Movva in Tulsa. In a procedure, that until recently was only available in Europe, Regenexx uses a person's own stem cells to regenerate bad tissue in places like knees, hips, shoulders, ankles and elbows.

"We take your own stem cells, the patient's own stem cells from a reservoir of stem cells. Because we all have stem cells in different reservoirs," said Dr. Venkatesh Movva.

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New Procedure Gives Tulsan A Chance To Walk Using His Own Stem Cells

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