Vision saved by first induced pluripotent stem cell treatment … – Concord Register
By Sykes24Tracey
iPS cells may help halt failing vision
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By Andy Coghlan
A woman in her 80s has become the first person to be successfully treated with induced pluripotent stem (iPS) cells. A slither of laboratory-made retinal cells has protected her eyesight, fighting her age-related macular degeneration a common form of progressive blindness.
Such stem cells can be coaxed to form many other types of cell. Unlike other types of stem cell, such as those found in an embryo, can be made from adult non-stem cells a discovery that in 2012.
Now, more than a decade after they were created, these stem cells have helped someone. at the RIKEN Laboratory for Retinal Regeneration in Kobe, Japan, and her team took skin cells from the woman and turned them into iPS cells. They then encouraged these to form retinal pigment epithelial cells, which are important for supporting and nourishing the retina cells that capture light for vision.
The researchers made a slither of cells measuring just 1 by 3 millimetres. Before in 2014, they first removed diseased tissue on her retina that was gradually destroying her sight. They then inserted the small patch of cells they had created, hoping they would become a part of her eye and stop her eyesight from degenerating.
Now the results are in. Published today, they show that the treatment hasnt made the womans vision any sharper, but it does seem to have prevented further deterioration with her vision now stable for more than two years. Since the graft, the woman says her vision is brighter.
Takahashi and her team have done incredible work, and deserve all the praise they get for this project, says , director of the Center for iPS Cell Research and Application at Kyoto University, who won the Nobel prize for and collaborated on this work. This is a landmark study and opens the door to similar treatments for many diseases, he says.
This first iPSC-derived retinal graft is an important landmark in the field of retinal regeneration, says at University College London, and head of a trial at Moorfields Eye Hospital in London of similar grafts made instead from human embryonic stem cells.
One worry about this approach is that turning the stem cells into new tissues could lead to cancer-causing genetic mutations though the team found no evidence of this in the treated woman. However, a trial of the technique in another person was cancelled in 2015, after tests revealed that the cells intended to be given to the man had developed genetic abnormalities.
But although it has taken many years to bring , many private centres around the world have been advertising unregulated treatments purporting to use stem cells for some time.
A second study published today shows just how badly some unregulated treatments described as stem cell therapies can go wrong. Three case reports of women given such treatments for age-related macular degeneration detail how one woman went blind and the vision of the other two became much worse.
All three ended up seeking emergency treatment in 2015, after each paid $5000 to a private clinic to receive injections of their own fatty tissue into their eyes.
Patients and physicians in the US should be made aware that not all stem cell clinics are safe, and that stem therapy as provided in private clinics in the US is unproven and potentially harmful, says at the University of Miamis Bascom Palmer Eye Institute, Florida, who subsequently treated two of the women.
Albini advises people to be suspicious of any procedure involving payment. Most legitimate research in the US does not require patients to pay for the experimental procedures, he says, adding that people should check whether a trial has been registered with the US Food and Drug Administration. Be aware that if it sounds too good to be true, it may indeed not be true.
Journal reference: New England Journal of Medicine, DOI: ;
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March 19th, 2017
Cutting-edge stem cell therapy proves safe, but will it ever be effective? – Science Magazine
By JoanneRUSSELL25
Masayo Takahashi (second from left) treated macular degeneration with retinal tissue grown from iPS cells.
Kyodo News/Contributor/getty images
By Dennis NormileMar. 15, 2017 , 5:00 PM
Its official: The first use of induced pluripotent stem (iPS) cells in a human has proved safe, if not clearly effective. Japanese researchers reported in this weeks issue of The New England Journal of Medicine (NEJM) that using the cells to replace eye tissue damaged by age-related macular degeneration (AMD) did not improve a patients vision, but did halt disease progression. They had described the outcome at conferences, but publication of the details is an encouraging milestone for other groups gearing up to treat diseased or damaged organs with the versatile replacement cells, which are derived from mature tissues.
This initial success is pretty momentous, says Alan Trounson, a stem cell scientist at the Hudson Institute of Medical Research in Melbourne, Australia. But the broader picture for iPS therapies is mixed, as researchers have retreated from their initial hopes of creating custommade stem cells from each patients tissue. That strategy might have ensured that recipients immune systems would accept the new cells. But it proved too slow and expensive, says Shinya Yamanaka of Kyoto University in Japan, who first discovered how to create iPS cells and is a co-author of the NEJM paper. He and others are now developing banks of premade donor cells. Using stocks of cells, we can proceed much more quickly and cost effectively, he says.
Even so, clinical work is progressing more quickly than I had expected, says Yamanaka, who did his groundbreaking work just a decade ago. His collaborator on this trial, Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe, Japan, had a head start. An ophthalmologist, Takahashi was familiar with the ravages of AMD, a condition that progressively damages the macula, the central part of the retina, and is the leading cause of blindness in the elderly.
Takahashi started investigating treatments for AMD in 2000, a time when the only cells capable of developing into all the tissues of the body had to be extracted from embryos. But she was stymied by immune reactions to these embryonic stem (ES) cells. When Yamanaka announced that he could induce mature, or somatic cells, to return to an ES celllike state, Takahashi quickly changed course to develop a treatment based on iPS cells.
Her team finally operated on the first patient, a 77-year-old Japanese woman with late-stage AMD, in September 2014. They took a sample of her own skin cells, derived iPS cells, and differentiated them into the kind of retinal cells destroyed by the disease. A surgeon then slipped a small sheet of the cells into the retina of her right eye.
An operation on a second patient was called off because a number of minor genetic mutations had crept into his iPS cells during processing, and uncontrolled growthcancerhas been a worry with such cells. These changes do not directly induce cancer, but we wanted to make safety the first priority, Yamanaka says. Also, Takahashi says, AMD drugs had stabilized the patients condition so there was no urgency in subjecting him to the risks of surgery, which include hemorrhaging and retinal damage.
Immediately after surgery the first patient reported her eyesight was brighter. Takahashi says the surgery halted further deterioration of her eye, even without the drug injections still being used to treat her other eye, and there were no signs of rejection of the graft as of last December.
Clinical work is progressing much more quickly than I expected.
The result is a proof of principle that iPS cellbased therapy is feasible, says Kapil Bharti, a molecular cell biologist at the U.S. National Institutes of Healths National Eye Institute in Bethesda, Maryland, who is also developing iPS cells for treating AMD. Takahashi says once her team gains more experience with the technique they will extend it to patients with earlier-stage AMD in an effort to preserve vision.
Last month, Takahashi won approval to try the procedure on another five patients with late-stage AMD. But this time, instead of using iPS cells derived from each patient, the team will draw on banked cells from a single donor. It takes time to create iPS cells, and a lot of time for the safety evaluation, Yamanaka says. It is also costly, at nearly $900,000 to develop and test the iPS cells for the first trial, Takahashi adds.
Using donor cells to create the iPS cells will make it more difficult to ensure immune compatibility. But Yamanaka says that donor iPS cells can be matched to patients based on human leukocyte antigen (HLA) haplotypessets of cell-surface proteins that regulate immune reactions. HLA-matched cells should require only small doses of immunosuppressive drugs to prevent rejection, Takahashi saysand perhaps none at all for transplantation into the immune-privileged eye.
Kyoto Universitys Center for iPS Cell Research and Application, which Yamanaka heads, has been developing an iPS cell bank. Just 75 iPS cell lines will cover 80% of the Japanese population through HLA matching, he says. Trounson, a past president of the California Institute for Regenerative Medicine, a stem cell funding agency, says banked iPS cells have advantages. Donor iPS cells may be safer than cells derived from older patients, whose somatic cells may harbor mutations. And Jordan Lancaster, a physiologist at the University of Arizona in Tucson, likes the speed of the approach. He is devising patches for heart failure patients based on iPS-derived myocardial cells that will be premanufactured, cryopreserved, and ready to use at a moments notice.
Patient-specific iPS cells will still have clinical uses. For one thing, Bharti says it will be difficult for cell banks to cover all HLA haplotypes. And a patients own iPS cells could be used to screen for adverse drug reactions, says Min-Han Tan, an oncologist at Singapores Institute of Bioengineering and Nanotechnology, who recently published a report on the approach.
Other human trials are not far behind. Yamanaka says his Kyoto University colleague Jun Takahashi (Masayo Takahashis husband) will launch trials of iPS-derived cells to treat Parkinsons disease within 2 years. Bharti hopes to start human trials of iPS cells for a different type of macular degeneration next year. And as techniques for making and growing iPS cells improve, researchers can contemplate treatments requiring not just 100,000 cells or sothe number in Takahashis retinal sheetsbut millions, as in Lancasters heart patches.
As clinical use approaches, Takahashi cautions that researchers need to keep public expectations realistic. For now, iPS treatments may help but wont fully reverse disease, she says. Regenerative medicine is not going to cure patients in the way they hope.
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March 18th, 2017
3 women blinded after receiving stem cell therapy for macular degeneration – ClickLancashire
By daniellenierenberg
The new report says the three women, in their 70s and 80s, paid $5,000 to be treated in 2015 for age-related macular degeneration. Participants can also report their concerns to the Office for Human Research Protections within the U.S. Department of Health and Human Services.
The "devastating outcomes" experienced by the women raise the "need for oversight of such clinics and for the education of patients by physicians and regulatory bodies", the paper said.
The women all suffered detached retinas, vision loss, and hemorrhages in their eyes.
"We don't mean to say all stem cell clinical studies are risky", coauthor Dr. Thomas Albini of the University of Miami told Reuters Health in a telephone interview.
Paul Knoepfler, a stem-cell scientist at the University of California at Davis who is a frequent critic of the clinics, said he didn't understand why the FDA and the NIH have not moved more aggressively to ensure patient safety. They sought treatment at a Florida clinic that had announced a study to treat the condition on clinicaltrials.gov, a federal database of research studies. Two out of the three patients found the trial through the website, which doesn't fully vet trials for scientific soundness. "Platelet count increased to 1.01m3 following the treatment and there were remarkable improvements in other symptoms", said Geeta Shroff, Stem Cell Specialist, Director, Nutech Mediworld. Stem cell clinics have cropped up all over the United States in recent years and are operating in a self-perceived regulatory loophole. Stem cells were then extracted from the fat and injected into their eyes. Albini says the complications could have come from injecting a contaminant into the eye, or from the fact that the stem cells may have turned into myofibroblasts after the injections, which are cells associated with scarring.
The Japanese case marks the first time anyone has given induced pluripotent stem (iPS) cells to a patient to treat any condition.
Legitimate medical research seldom requires patients to pay and, in the case of eye treatments, only one eye is treated at a time so doctors can gauge its effectiveness, the Kuriyan team said.
Although the women had moderate vision loss prior to the stem cell treatments, a year later their vision ranged from total blindness to 20/200, which is considered legally blind.
And even if the interventions were done well, they say, there is no evidence that they could have restored the patients' vision. They first cultivate stem cells to form the retinal pigmented epithelial cells that are needed to restore a damaged retina.
Shoddy stem cell preparation may have led to some of the complications, said the study authors.
The episode, described Wednesday in an article in the New England Journal of Medicine, represents one of the most egregious examples of patient injury involving a stem-cell clinic. The company also noted that it does not now treat eye patients.
The paper also mentions that the women believed that they were taking part in a clinical trial because they were aware of the clinic's work on the ClinicalTrials.gov website run by the U.S. National Library of Medicine. In other words, the company claims the study was stopped before patients were enrolled. In fact, doctors have done bone marrow transplant, a procedure where stem cell transplantation is performed.
"There's this perception that there are all these stem cell therapies out there that are close to clinical application that. are being held back by regulators and if they just step back, there would be all these treatments", he said. However, it can be hard for patients to distinguish between trials that are legitimate, and those that are not, the authors wrote.
"There's no excuse for not designing a trial properly and basing it on preclinical research", added study Jeffrey Goldberg, also a study author, of Stanford University's School of Medicine.
Researchers from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg and an global team have now identified an ingenious mechanism by which the body orchestrates the regeneration of red and white blood cells from progenitor cells.
See if a trial is affiliated with an academic medical center - that's a good sign it is legitimate, they say.
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March 18th, 2017
Researchers develop new animal model to study rare brain disease – Medical Xpress
By JoanneRUSSELL25
March 17, 2017 Left: Cross-sectional view of the cerebrum in normal ferret. Neurons are localized in the cerebral cortex, the surface layer of the cerebrum. Since the surface of the cerebrum has folds (gyri), the layer containing neurons winds on its way. Right: Cross-sectional view of the cerebrum in TD ferret. Clusters of neurons (indicated by arrows) are found deep in the cerebrum, which are not detected in the cerebrum of normal ferret. They are called 'periventricular nodular heterotopia,' PNH. In addition, in the surface layer, a larger number of smaller folds (gyri) are seen than normal (indicated by asterisks). They are called polymicrogryri. Credit: Kanazawa University
Thanatophoric dysplasia (TD) is an intractable disease causing abnormalities of bones and the brain. In a recent study of ferrets, which have brains similar to those of humans, researchers using a newly developed technique discovered that neuronal translocation along radial glial fibers to the cerebral cortex during fetal brain development is aberrant, suggesting the cause underlying TD.
In TD cases, the limb and rib bones are shorter than normal, and brain abnormalities manifest, including polymicrogyria and periventricular nodular heterotopia. Previous research has determined that a gene, fibroblast growth factor receptor 3 (FGFR3), is responsible. However, as a result of TD rarity and the difficulty of obtaining brain samples from human patients, the pathophysiology of TD is largely unknown, and effective therapy has not been established.
The present research team of Kanazawa University generated an animal model of TD using ferrets that reproduces the brain abnormalities found in human TD patients. By using this animal model, the team elucidated the formation process of polymicrogyria, one of the abnormalities found in the TD brain. The team has also investigated the formation process of PNH, the other brain abnormality found in human TD patients.
First, PNH was analyzed in terms of composing cell types to reveal that a large number of neurons but few glial cell exist in PNH. In a healthy brain, neurons are found in the cerebral cortex near the brain surface. The researchers believe that during fetal brain development, PNH formation might be induced by the inability of neurons to translocate themselves to the cerebral cortex. The researchers found that the spatial arrangement of radial glial cells was distorted; radial glial fibers are believed to serve as the "track" for neurons to translocate themselves. Thus, the distortion of radial glial fibers seems to be a reason for aberrant localization of neurons.
Research on abnormalities of bones in TD is progressing with iPS cells at Kyoto University, and it is expected that the whole aspect of TD with brain and bone abnormalities would be elucidated and that the therapeutic methods would be developed. The present study on PNH was only possible using the experimental technique for ferrets developed by the research team. This animal model technique could also contribute to studies of other neurological diseases that have been difficult to investigate with conventional model animals.
Explore further: Researchers discover a gene's key role in building the developing brain's scaffolding
More information: Naoyuki Matsumoto et al, Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals, Human Molecular Genetics (2017). DOI: 10.1093/hmg/ddx038
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March 18th, 2017
Team Deciphers How the Body Controls Stem Cells – Scicasts (press release) (blog)
By Sykes24Tracey
Luxembourg (Scicasts) Stem cells are unspecialized cells that can develop into any type of cell in the human body. So far, however, scientists only partially understand how the body controls the fate of these all-rounders, and what factors decide whether a stem cell will differentiate, for example, into a blood, liver or nerve cell. Researchers from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg and an international team have now identified an ingenious mechanism by which the body orchestrates the regeneration of red and white blood cells from progenitor cells. "This finding can help us to improve stem cell therapy in future," says Dr. Alexander Skupin, head of the "Integrative Cell Signalling" group of LCSB. The LCSB team has published its results in the scientific journal PLOS Biology.
Although all cells in an organism carry the same genetic blueprints -- the same DNA -- some of them act as blood or bone cells, for example, while others function as nerve or skin cells. Researchers already understand quite well how individual cells work. But how an organism is able to create such a diversity of cells from the same genetic template and how it manages to relocate them to wherever they are needed in the body is still largely unknown.
In order to learn more about this process, Alexander Skupin and his team treated blood stem cells from mice with growth hormones and then watched closely how these progenitor cells behaved during their differentiation into white or red blood cells. The researchers observed that the cells' transformation does not occur in linear, targeted fashion, but rather more opportunistically. Each progenitor cell adapts to the needs of its environment and integrates itself into the body where new cells are needed. "So, it is not as though the cell takes a ticket at the beginning of its differentiation and then travels straight to its destination. Rather, it gets off frequently to look around and see which line is best to take," Alexander Skupin explains. By this clever mechanism, a multicellular organism can adapt the regrowth of new cells to its current needs. "Before progenitor cells differentiate once and for all, they first lose their stem cell character and then check, as it were, which cell line is currently in demand. Only then do they develop into the cell type that best suits their characteristics and which prevails in their environment," Alexander Skupin says.
The researcher likens this step to a game of roulette, where the different types of cells can be thought of as the differently numbered slots in the roulette wheel that catch the ball. "When the cells lose their stem cell character, they are quasi thrown into the roulette wheel, where they first bounce around aimlessly. Only when they have found the right environment do the cells then drop into that niche - like the roulette ball falling into a numbered slot - and differentiate definitively." This way, the body can orchestrate its cell regeneration and at the same time prevent stem cells from being misdirected too early. "Even if a cell takes a wrong turn, it is ultimately sorted out again if its characteristics are unsuitable for the niche, or slot, it has landed in," says Skupin.
With their study, Alexander Skupin and his team have shown for the first time that a progenitor cell's fate is not clearly predetermined and does not follow a straight line. "This observation contradicts the current doctrine that stem cells are programmed to follow a certain lineage from the beginning," Alexander Skupin says. The researcher is furthermore convinced that the processes are similar for other progenitor cells. "In the lab, we have observed the same differentiation pattern in so-called iPS cells, or induced pluripotent stem cells, which can transform into many different types of cells."
This knowledge can help the researchers to improve the effectiveness of therapies in future. Stem cell therapy involves administering a patient his or her own body's stem cells in order to replace other cells that have died as a result of an affliction such as Parkinson's disease. While this promising treatment method has been intensively researched over many years, there has so far been only limited practical success in endogenous stem cell therapy. It is also highly controversial, since it is frequently accompanied by severe side effects and it cannot be ruled out that some cells might degenerate and lead to cancer. "Because we now have a better understanding of how the body influences the direction in which stem cells differentiate, we can hopefully control this process better in future," Alexander Skupin concludes.
Article adapted from a University of Luxembourg news release.
Publication: Cell Fate Decision as High-Dimensional Critical State Transition. Mitra Mojtahedi et al. PLoS Biol. (2016): Click here to view.
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March 18th, 2017
3 Women Blinded By Unproven Stem Cell Treatments – NPR
By NEVAGiles23
Scientists have long hoped that stem cells might have the power to treat diseases. But it's always been clear that they could be dangerous too, especially if they're not used carefully.
Now a pair of papers published Wednesday in the New England Journal of Medicine is underscoring both the promise and the peril of using stem cells for therapy.
In one report, researchers document the cases of three elderly women who were blinded after getting stem cells derived from fat tissue at a for-profit clinic in Florida. The treatment was marketed as a treatment for macular degeneration, the most common cause of blindness among the elderly. Each woman got cells injected into both eyes.
In a second report, a patient suffering from the same condition had a halt in the inexorable loss of vision patients usually experience, which may or may not have been related to the treatment. That patient got a different kind of stem cell derived from skin cells as part of a carefully designed Japanese study.
The Japanese case marks the first time anyone has given induced pluripotent stem (iPS) cells to a patient to treat any condition.
"These two reports are about as stark a contrast as it gets," says George Q. Daley, Harvard Medical School's dean and a leading stem cell researcher. He wrote an editorial accompanying the two papers. "It's really striking."
The report about the three women in their 70s and 80s who were blinded in Florida is renewing calls for the Food and Drug Administration to crack down on the hundreds of clinics that are selling unproven stem cell treatments for a wide variety of medical conditions, including arthritis, autism and stroke.
"One of the big mysteries about this particular case and the mushrooming stem cell clinic industry more generally is why the FDA has chosen to effectively sit itself out on the sidelines even as this situation overall grows increasingly risky to patients," says Paul Knoepfler, a University of California, Davis, stem cell researcher who has studied the proliferation of stem cell clinics.
"The inaction by the FDA not only puts many patients at serious risk from unproven stem cell offerings, but also it undermines the agency's credibility," Knoepfler wrote in an email.
In response to a query from Shots, an FDA spokeswoman wrote in an email that the agency is in the process of finalizing four new guidelines aimed at clarifying how clinics could use stem cells as treatments. The agency also noted that it had previously issued a warning to patients.
In the meantime, "consumers are encouraged to contact FDA and the appropriate state authorities in their jurisdictions to report any potentially illegal or harmful activity related to stem cell based products," the FDA email says.
Other researchers say the cases should stand as a warning to patients considering unproved stem cell treatments, especially those tried outside carefully designed research studies.
"Patients have to be wary and tell the difference between the snake oil salesmen who are going to exploit them and the kind of slow, painstaking legitimate clinical trials that are also going on," Daley says.
The New England Journal of Medicine report did not name the Florida clinic, but noted that the treatment was listed on a government website that serves as a clearinghouse for research studies. The sponsor is listed as Bioheart, Inc., which is part of U.S. Stem Cell Inc. in Sunrise, Fla.
Kristen Comella, the scientific director of U.S. Stem Cell, would not discuss the cases. "There were legal cases associated with eye patients that were settled under confidentiality, so I am not permitted to speak on any details of those cases due to the confidentiality clause," Comella said by phone.
She acknowledged, however, that the clinic had been performing the stem cell procedures. They were discontinued after at least two patients suffered detached retinas, she says.
But Comella defended the use of stem cells from fat tissue to treat a wide variety of other health problems.
"We have treated more than 7,000 patients and we've have had very few adverse events reported. So the safety track record is very strong," Comella says. "We feel very confident about the procedures that we do, and we've had great success in many different indications."
According to the New England Journal of Medicine report, The Florida clinic was using adult stem cells, which circulate in various parts of the body, including in fat tissue. While those cells may someday be turn out to be useful for treating disease, none have been proven to work.
The body produces a variety of stem cells. The kind that have generated the most excitement and controversy are human embryonic stem cells, which are derived from early human embryos and can be coaxed to become any kind of cell in the body.
Scientists are also excited about iPS cells, which can be made in the laboratory by turning any cell in the body, such as skin cells, into cells that resemble embryonic stem cells.
Those are the cells that were tested by the Japanese scientists. The stem cells were converted into retinal pigment epithelium (RPE) cells, which are the cells that are destroyed by macular degeneration.
"This represents a landmark," says Daley. "It's the first time any patient has been treated with cellular derivatives of iPS cells. So it's definitely a world first."
Daley noted that the scientists only treated one of the patient's eyes in case something went wrong, to ensure remaining vision would not be threatened in the other eye.
After at least a year, no complications had occurred and the patient had not experienced any further deterioration of vision in the treated eye. While that is promising, more patients would have to be treated and followed for much longer to know whether that approach is successful, Daley says.
"Given that macular degeneration is the most frequent cause of vision loss and blindness in the elderly and our population is aging, the prevalence of macular degeneration is going up dramatically," Daley says. "So to be able to preserve or even restore sight would be a really remarkable medical advance."
Despite the potentially encouraging results with the first patient, Daley noted that the Japanese scientists decided not to treat a second patient and suspended the study. That's because they discovered worrisome genetic variations in the RPE cells they had produced for the second patient.
"They weren't certain these would cause problems for the patient, but they were restrained enough and cautious enough that they decided not to go forward," Daley says. "That's what contrasts so markedly with the approach of the second group, who treated the three patients with an unproven stem cell therapy that ended up have devastating effects on their vision."
In this case, the New England Journal of Medicine report says, patients paid $5,000 each to receive injections of solutions that supposedly contained stem cells that were obtained from fat removed from their abdomens through liposuction.
Even though the safety and effectiveness of this procedure is unknown, all three patients received injections in both eyes.
"That's what led to these horrible results," says Thomas Albini, a retina specialist at the University of Miami's Bascom Palmer Eye Institute, who helped write the report.
Before the procedure, all three women still had at least some vision. Afterwards, one woman was left completely blind while the other two were effectively blind, Albini and his colleagues reported.
The cases show that patients need to be warned that something that "sounds too good to be true may indeed be too good to be true and may even be horrible," Albini says.
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March 16th, 2017
Researchers decipher how the body controls stem cells – Science Daily
By Sykes24Tracey
Researchers decipher how the body controls stem cells Science Daily "In the lab, we have observed the same differentiation pattern in so-called iPS cells, or induced pluripotent stem cells, which can transform into many different types of cells." This knowledge can help the researchers to improve the effectiveness of ... |
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March 15th, 2017
Waiting to Reprogram Your Cells? Don’t Hold Your Breath – Scientific American
By LizaAVILA
Guiding a recent tour of a Kyoto University lab, a staff member holds up a transparent container. Inside are tiny pale spheres, no bigger than peas, floating in a clear liquid. This is cartilage, explains the guide, Hiroyuki Wadahama. It was made here from human iPS cells.
A monitor attached to a nearby microscope shows a mass of pink and purple dots. This is the stuff from which the cartilage was grown: induced pluripotent stem cells, often called iPS cells. Scientists can create these seemingly magical cells from any cell in the body by introducing four genes, in essence turning back the cellular clock to an immature, nonspecialized state. The term pluripotent refers to the fact iPS cells can be reprogrammed to become any type of cell, from skin to liver to nerve cells. In this way they act like embryonic stem cells and share their revolutionary therapeutic potentialand as such, they could eliminate the need for using and then destroying human embryos. Also, iPS cells can proliferate infinitely.
They can also give rise, however, to potentially dangerous mutations, possibly including ones that lead to cancerous tumors. Thus, iPS cells are a double-edged swordtheir great promise is tempered by risk. Another problem is the high cost of treating a patient with his or her own newly reprogrammed cells. But now Japanese researchers are trying a different approach.
When Kyoto University researcher Shinya Yamanaka announced in 2006 that his lab had created iPS cells from mouse skin cells for the first time, biologists were stunned. In 2007, along with James Thomson of the University of WisconsinMadison, Yamanaka repeated the feat with human skin cells. Many hailed the opening of an entirely new field of personalized regenerative medicine. Need new liver cells? No problem. Patients could benefit from having their own cells reprogrammed into ones that could help treat disease, potentially eliminating the prospect of immune rejection. In 2012 Yamanaka shared the Nobel Prize in Physiology or Medicine with John Gurdon for discovering that mature cells can be converted to stem cells. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy, the Nobel judges wrote. To capitalize on the discovery, Kyoto University set up the $40-million Center for iPS Cell Research and Application (CiRA), which Yamanaka directs.
A decade after the Yamanaka teams groundbreaking discoveries, however, iPS cells have retreated from the headlines; to the layperson, progress seems scant. There has only been one clinical trial involving iPS cells, and it was halted after a transplant operation on just one patienta Japanese woman in her 70s with macular degeneration, a condition that can lead to blurry vision or partial blindness. Doctors at Kobe City Medical Center General Hospital used her skin cells to grow iPS cells, which were reprogrammed into retinal cells and implanted in her eye. The treatment stopped the degeneration but the trial was halted in 2015 because genetic mutations were detected in another batch of iPS cells intended for another patient. Regulatory changes, under which the Japanese government allowed the distribution of iPS cells for clinical use, also prompted researchers to switch the study to a more efficient process of using cells from third-party donors instead of using a patients own cells. The Japanese government has a lot of incentives to considerwere developing a new science, a new technology and also a new economic market, says CiRA spokesperson Peter Karagiannis. So theres the ethical issues, but theres also money to be made. How do we balance the two?
The Kobe clinical trial had a lot riding on it. And the setback followed a major stem cell scandal in which biologist Haruko Obokata of the Riken Center for Developmental Biology was found to have falsified data in studies, published in 2014, that claimed a new method of achieving pluripotency. Then, earlier this year, Yamanaka had to apologize at a news conference after it was discovered that a reagent used to create iPS cells at CiRA was mislabeled, which could mean the wrong reagent was used. Although the mix-up is being examined, the center has halted supplies of some of its iPS cells to researchers across Japan; the error also set back by a few years a CiRA project to produce clinical-grade platelets from iPS cells.
But Yamanaka says he remains focused on the bigger picture of iPS cells and is still optimistic they can not only help researchers but may be key to transformative clinical therapies. CiRA still has a bank of tens of millions of iPS cells that have already been reset and checked for safety, so they can be used in patient applications. In terms of regenerative medicine, things have gone quicker than I expected, Yamanaka says, adding, iPS cells have exceeded expectations because of their potential for disease modeling, which allows us to elucidate unknown disease mechanisms, and drug discovery.
Those hoping for quick clinical success should remember it takes time for revolutionary treatments to go from lab bench to bedside, says Andras Nagy, a stem cell researcher at Mount Sinai Hospitals LunenfeldTanenbaum Research Institute in Toronto, who has not been directly involved in Yamanakas work. If you fully appreciate the paradigm-shifting nature of iPS cells, tremendous progress has in fact been made over the past 10 years, says Nagy, who in 2009 established a method of creating stem cells without using viruses (which had initially been used to deliver reprogramming genes into targeted cells). By comparison, penicillin was discovered as an antibiotic in 1928, but it was not available in the clinic until the early 1940s.
Researchers in Japan are meanwhile using iPS cell technology to pave the way to better drugs. For instance, CiRAs Kohei Yamamizu recently reported developing a cellular model of the bloodbrain barrier made entirely from human iPS cells. It could become a useful tool for testing drugs for brain diseases.
All eyes, however, are back on Kobe City Medical Center General Hospital, which is resuming its retina trialthis time with iPS cells from donors instead of cells from patients themselves. Using CiRAs bank of iPS cells, there are significant time and cost savingsit could be one fifth the cost of cell preparation and patient transplant or less. The initial study, with its personalized approach, reportedly cost about $875,000 for just one patient. We plan to evaluate the efficacy of transplanting the [donor] cells and consider the feasibility of using this method as a routine treatment in the future, accessible to the wider society, study co-leader Masayo Takahashi of the RIKEN Center for Developmental Biology said at a February press conference in Kobe. Her husband Jun Takahashi, a researcher at CiRA, is also planning to use donor-derived iPS cells for a clinical applicationto help treat patients with Parkinsons disease.
Nagy admits the promise of personalized cell regeneration is probably too costly for mainstream use, and he believes genomic editingin which DNA is inserted or deletedis key to safe iPS cell implants. For his part, Yamanaka is cautiously optimistic about iPS cells as a therapeutic tool.
Regenerative medicine and drug discovery are the two key applications for iPS cells, Yamanaka says. With the use of iPS cell stock, we are now able to work quicker and cheaper, so thats the challenge going forward.
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March 15th, 2017
Applied StemCell Announces the Appointment of Dr. Michele Calos, Stanford Professor and Vice President of the … – Yahoo Finance
By daniellenierenberg
MILPITAS, Calif.--(BUSINESS WIRE)--
Applied StemCell (ASC), a leading stem cell and genome-editing company with a goal to advance genome editing and stem cell technologies for biomedical research and clinical applications, welcomes Dr. Michele Calos as a member of the companys Scientific Advisory Board (SAB).
Dr. Michele Calos is a Professor of Genetics at the Stanford University School of Medicine, Vice President of the American Society of Gene and Cell Therapy, and has served as an Advisory Committee member for the US FDA, grant review panels for the NIH and NSF, and on numerous editorial review committees of scientific journals. She is a leader in the field of molecular genetics and has developed several novel vector systems for genetic manipulation of mammalian cells. In particular, she developed novel methods for sequence-specific integration in mammalian cells using the C31 phage integrase system. A similar integrase system was also successfully used in site-specific integration in human ES and iPS cells. For this work, Dr. Calos holds a joint patent application with Applied StemCells Chief Scientific Officer, Dr. Ruby Yanru Chen-Tsai and several other Stanford researchers. Dr. Calos pioneering work with C31 integrase also set the scientific stage for ASCs TARGATT integrase technology, which was co-developed by Dr. Chen-Tsai and Dr. Liqun Luo of Stanford University for gene modification in mouse models.
We are extremely pleased to have Dr. Calos join as a member of our scientific advisory board. With her impressive background in integrase gene modification technology and gene therapy, Dr. Calos will be an invaluable guide in furthering expansion of our genome editing platforms and our gene/cell therapy pipeline, said Ruby Yanru Chen-Tsai, Ph.D., Co-founder and Chief Scientific Officer of Applied StemCell.
Dr. Calos and her research team are currently focused on gene therapy and genome engineering for the treatment of Duchenne and Limb Girdle Muscular Dystrophies and developing further novel strategies for gene and cell therapy.
About Applied StemCell, Inc.
Applied StemCell, Inc. is a leading stem cell and gene-editing company focused on the development of products and therapeutics that are enabled by its proprietary gene editing platform technologies TARGATT and CRISPR/Cas9. For more information, please visit http://www.appliedstemcell.com.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170306005063/en/
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March 12th, 2017
Applied StemCell Announces the Appointment of Dr. Michele Calos, Stanford Professor and Vice President of the … – Business Wire (press release)
By Sykes24Tracey
MILPITAS, Calif.--(BUSINESS WIRE)--Applied StemCell (ASC), a leading stem cell and genome-editing company with a goal to advance genome editing and stem cell technologies for biomedical research and clinical applications, welcomes Dr. Michele Calos as a member of the companys Scientific Advisory Board (SAB).
Dr. Michele Calos is a Professor of Genetics at the Stanford University School of Medicine, Vice President of the American Society of Gene and Cell Therapy, and has served as an Advisory Committee member for the US FDA, grant review panels for the NIH and NSF, and on numerous editorial review committees of scientific journals. She is a leader in the field of molecular genetics and has developed several novel vector systems for genetic manipulation of mammalian cells. In particular, she developed novel methods for sequence-specific integration in mammalian cells using the C31 phage integrase system. A similar integrase system was also successfully used in site-specific integration in human ES and iPS cells. For this work, Dr. Calos holds a joint patent application with Applied StemCells Chief Scientific Officer, Dr. Ruby Yanru Chen-Tsai and several other Stanford researchers. Dr. Calos pioneering work with C31 integrase also set the scientific stage for ASCs TARGATT integrase technology, which was co-developed by Dr. Chen-Tsai and Dr. Liqun Luo of Stanford University for gene modification in mouse models.
We are extremely pleased to have Dr. Calos join as a member of our scientific advisory board. With her impressive background in integrase gene modification technology and gene therapy, Dr. Calos will be an invaluable guide in furthering expansion of our genome editing platforms and our gene/cell therapy pipeline, said Ruby Yanru Chen-Tsai, Ph.D., Co-founder and Chief Scientific Officer of Applied StemCell.
Dr. Calos and her research team are currently focused on gene therapy and genome engineering for the treatment of Duchenne and Limb Girdle Muscular Dystrophies and developing further novel strategies for gene and cell therapy.
About Applied StemCell, Inc.
Applied StemCell, Inc. is a leading stem cell and gene-editing company focused on the development of products and therapeutics that are enabled by its proprietary gene editing platform technologies TARGATT and CRISPR/Cas9. For more information, please visit http://www.appliedstemcell.com.
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March 7th, 2017
Stem Cell Research & Therapy | Home page
By LizaAVILA
"Stem cells have enormous potential for alleviating suffering for many diseases which currently have no effective therapy. The field has progressed to the clinic and it is important that this pathway is underpinned by excellent science and rigorous standards of clinical research. The journal provides an important avenue of publication in translational aspects of stem cell therapy spanning preclinical studies, clinical research and commercialization."
Timothy O'Brien,Editor-in-Chief,Stem Cell Research & Therapy
"The study of stem cells is one of the most exciting areas of contemporary biomedical research. We believe that Stem Cell Research & Therapy will act as a highly active forum for both basic and translational research into stem cell biology and therapies. Specifically, by developing this forum for cutting edge research, we hope that Stem Cell Research & Therapy will play a significant role in bringing together the critical information to synergize stem cell science with stem cell therapies."
Rocky S Tuan,Editor-in-Chief,Stem Cell Research & Therapy
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Stem Cell Research & Therapy | Home page
ISSCR 2017 – Drug Target Review – Drug Target Review
By NEVAGiles23
event
Date: 14 June 2017 - 17 June 2017
Location: Boston Convention and Exhibition Center 415 Summer Street Boston 02210 United States
Website: ISSCR2017.org
Email: [emailprotected]
Telephone: +1 224-592-5700
The International Society for Stem Cell Research (ISSCR) 2017 annual meeting will be held 14-17 June in Boston, Mass., U.S., at the Boston Convention and Exhibition Center. The meeting brings together 4000 stem cell researchers and clinicians from around the world to share the latest developments in stem cell research and regenerative medicine. In a series of lectures, workshops, poster presentations, and a dynamic exhibition floor, researchers focus on recent findings, technological advances, trends, and innovations that are realizing progress in using stem cells in the discovery and validation of novel treatments.
In 2017, the ISSCR is expanding its translational and clinical programming with two half-day, pre-meeting educational sessions geared toward bringing new therapies to the clinic. The Workshop on Clinical Translation (WCT) and the Clinical Advances in Stem Cell Research (CASC) programs are designed for scientists and physicians interested in learning more about the process of developing stem cell-based therapies and advances in stem cell applications in the clinic.
The Presidential Symposium recognizes a decade of progress in iPS cell research and application with a distinguished lineup of speakers including Shinya Yamanaka, discoverer of iPSCs. Additional plenary presentations include distinguished speakers from around the world focusing on organoids and organogenesis, the making of tissues and organs; stem cells and cancer; chromatin and RNA biology; stress, senescence and aging; tissue regeneration and homeostasis; and the frontiers of cell therapy.
Concurrent sessions feature new and innovative developments across the breadth of the field, and incorporate more than 100 abstract-selected speakers. Disease modelling, tissue engineering, stem cell niches, epigenetics, hematopoietic stem cells, and gene modification and gene editing are just a few of the 28 topic areas presented.
Other meeting offerings include career development sessions and networking opportunities. A full listing of the ISSCR 2017 meeting programming can be found at ISSCR2017.org.
Map
42.3461949 -71.04563680000001
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March 2nd, 2017
What’s the Catch: The Fountain of Youth – Paste Magazine
By daniellenierenberg
Scientist Juan Carlos Izpisua Belmonte from the Salk Institute in La Jolla, California, claims that the aging process may reversible: Our study shows that aging may not have to proceed in one single direction. With careful modulation, aging might be reversed.
Izpisua Belmonte attests that he implemented a new form of gene therapy on mice that were given a genetic disorder called progeria. After six weeks of treatment, the animals looked youngerand not only that, they had straighter spines, better cardiovascular health, healed more quickly when injured and actually lived longer.
How Its Done The rejuvenating treatment performed on the mice manipulates adult cells, such as skin cells, and turns them back into powerful stem cells (similar to what is seen in embryos). These powerhouses are referred to as induced pluripotent stem (iPS) cells and have the ability to multiply and transform into any cell type in the body; in fact, in trial tests, Izpisua Belmonte says iPS cells are being designed to provide organs and limbs for patients. He claims that his latest study is the first to show that the same technique can be used on other cells to rewind the clock and make them look younger. Izpisua Belmonte explains, The treatment involved intermittently switching on the same four genes that are used to turn skin cells into iPS cells. The mice were genetically engineered in such a way that the four genes could be artificially switched on when the mice were exposed to a chemical in their drinking water.
What This Means: This finding at the Salk Institute suggests that aging may not have to proceed in one directionin fact, Izpisua Belmonte states that it may actually be reversible. Although tests have not been conducted on humans yet, he predicts that applications via creams or injections are a decade away.
This rejuvenating treatment may not lead to immortality, but due to a growing body of evidence, scientists at the Salk Institute theorize that aging is driven by an internal genetic clock that actively causes our body to enter a state of decline. In developing this technology, it is hoped that future treatments designed will slow the ticking of this internal clock and ultimately increase life expectancy.
Whats the Catch? Dr. Sidney Chiu, a 5th year resident at the University of Toronto, thinks this information should be taken with a grain of salt: The findings are promising, but nowhere near ready for the front lines of healthcare. These experiments were done in highly controlled settings on genetically modified mice. If this finding were true, it would be worthy of a Nobel Prize because it would be akin to uncovering the Holy Grail. Chiu elaborates, If you can induce iPS cells, you have the basic building blocks to regenerate anything in the body. But this is far beyond any current medical science we have.
There are also numerous issues to address concerning the study: firstly, the mice are bred in labs for these types of tests, so the variables are controlled from the outset to attain desired results. Chiu adds, In the real world, you cannot turn specific genes on and off using treated water on mice in the wild, let alone humans. There isnt one specific gene for aging; I would be cautious about this scientists claims that isolating merely four could unlock the key to anti-aging. Even if we were just talking about reviving skin tissue, if his findings were true, it would be a breakthrough.
Chiu says that while it is technically possible to alter genetic material when humans are in an embryonic state, that wasnt done here (gene editing research in human embryos is currently allowed in Sweden China, and the United Kingdom. The United States doesnt currently have any legal prohibitions against it).
But its not to say that all of this is in the realm of science fiction; Chiu offers knowledge of research being conducted specifically for telomeres and their relationship to aging. Think of telomeres as the plastic caps that protect your shoelaces from fraying. The laces would be our chromosomes, the recipe for making a living thing. In fact, telomeres have an important role; they protect genetic material from damage that could otherwise lead to diseases or cell death. But because the number of cell divisions in telomeres is finite, once they become shorter (in length) and can no longer reproduce, it causes tissues to degenerate and eventually die. It is theorized that this process may contribute to the human aging process. So scientists are trying to find ways to extend the length of telomeres.
Izpisua Belmonte says that chemical approaches (via creams or injections) might be in human clinical trials to rejuvenate skin, bones and muscle within the next decade. However, from his perspective as a frontline healthcare worker, Chiu believes that we may just have to wait a bit longer than that before such innovations are accessible to everyone.
Main Photo by Thomas Rydberg, CC-BY
Tiffany Leigh is a Toronto-based food, travel, and science writer.
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February 21st, 2017
A key ion channel may SLACK off in ALS – ALS Research Forum
By Sykes24Tracey
Slacking off in ALS? Mutant SOD1 may partially close the SLACK ion channel resulting in increased excitability in some neurons (Zhang et al., 2017).[Image: NIGMS.]
Increased activity in the motor cortex of the brain may occur in most forms of ALS (see September 2015 news). But whether this hyperexcitability contributes to the disease remains an open question.
Now, researchers at Yale University make the case that ALS-linked mutant SOD1 may downregulate a key sodium-gated potassium ion channel, known as SLACK, through an apoptosis signal-regulatingkinase1 (ASK1)-based mechanism (Zhang et al., 2017).
The findings may help explain how motor neuron hyperexcitability occurs in ALS. These changes in excitability may contribute to disease pathogenesis and may underlie fasciculations, one of the earliest clinical manifestations of the disease.
The question is whether this pathway is the primary way that SOD1 mutations cause disease, said Steve Vucic of the University of Sydney, who was not involved in the study. If so, [there] is a tremendous opportunity for developing treatments against these kinase pathways.
The study is published on January 24 in the Journal of Neuroscience.
Excitement builds
Neuronal hyperexcitability emerged in recent years as an early and potentially unifying stepin ALS, due to its detection in a number of sporadic and genetic forms. While the evidence is still not yet conclusive, some studies suggest that this prolonged excitation can lead to toxicity, strengthening the case that these changes in excitability may contribute to the disease (Fritz et al., 2013; Hadzipasic et al., 2014).
How hyperexcitability occurs in ALS remains unclear. But a growing number of studies suggest that mutant SOD1 may be involved, at least in some cases of the disease (Wainger et al., 2014; van Zundert et al., 2008).
Researchers at Yale University, led by Leonard Kaczmarek and Arthur Horwich, wondered whether mutant SOD1 could trigger hyperexcitability in motor neurons by downregulating a key membrane-bound ion channel called SLACK (sequence like a calcium-activated K channel), also known as KCNT1 or KNa1.1.
SLACK is a key regulator of excitability that helps neuronsreturn to the resting state upon firing. Its widely expressed in the CNS and its dysfunction has also been implicated in neurological diseases including Fragile X and epilepsy (Barcia et al., 2012; Heron et al., 2012; Martin et al., 2014).
Hyperexcitability in the bag. Researchers use sea slug bag cell neurons to study underlying hyperexcitability mechanisms. [Image: Kabir et al., 2001 under a CC-BY-NC-SA license.]
To investigate this question, first co-authors Yalan Zhang and Weiming Ni turned to the neuronalmodel system, the sea slug Aplysia. The system gained recognition in the 1960s for its role in providing Eric Kandel Nobel Prize-winning insights into learning and memory formation.
The approachinvolves the manipulation and study of bag cell neurons, very large neuroendocrine cells in the sea slugs abdomen that control egg laying. The really big advantage is that, because of their size, you can inject materials into them and then use a very fine microelectrode to record changes in excitability, all without any disturbance of the cytoplasm, Kaczmarek said.
The researchers compared the activity of potassium channels in bag cell neurons in the presence or absence of wild-type or mutant SOD1, including soluble oligomers of increasing size. They found that SOD1 or mutant SOD1 G85R monomers had no effect. But when they injected SOD1 G85R oligomers, they observed a reduction in outward potassium currents by 20-30%. This drop occured within 10 minutes and increased with larger oligomer size.
Whats more, SOD1 G85R oligomers increased excitability of these neurons. Injection of these soluble 300 kDa protein complexes decreased the neurons resting membrane potential and increased its susceptibility to firing in response to applied stimuli, they found.
Further experiments identified the SLACK channel as the one most likely to have been affected by mutant SOD1, because neurons pretreated with siRNA against SLACK mitigated the effect of these protein complexes in these neurons.
Together, the results suggest that soluble mutant SOD1 oligomericcomplexes may lead to hyperexcitability due to partial closure of SLACK, a key sodium-gated potassium channel that helps neurons return to their resting state upon firing.
ASK1ing for trouble
How could mutant SOD1 downregulateSLACK? The researchers suspected that these effects may be triggered by ASK1, a key kinase that has been previously implicated in the destruction of motor neurons in the disease (Raoul et al., 2002).
ASK1 has been shown to mediate key effects of mutant SOD1 in mouse models of the disease including ER stress and disruption of axonal transport (Lee et al., 2016; Song et al., 2013). In addition, inhibitingthis pathway appears to extend the survival of a SOD1 G93A mouse model of the disease (Fujisawa, et al. 2016).
To investigate this possibility, the researchers blocked ASK1 signaling and determined the impact of SOD1 oligomeric complexes on potassium channel activity. They found that the suppression of outward potassium current could be abolished by pre-treatment with an inhibitor of the apoptosis signaling regulating kinase ASK1. Similar effects were achieved with an inhibitor of one of ASK1s downstream targets, JNK.
The results, Kaczmarek said, suggest that mutant SOD1 oligomericcomplexessuppressSLACK channels in neurons through a ASK1-based mechanism, causing hyperexcitability.
Its an attractive idea, says Massachusetts General Hospitals Brian Wainger, who was not involved in the study. The findings may provide a potentially direct mechanistic connection between mutant SOD1 and motor neuron hyperexcitability in ALS.
Mind your Potassium and KCNQs. Researchers are evaluating Kv 7.2 potassium channel activators including retigabine (orange) in hopes to reduce hyperexcitability in people with the disease. More specific channel modulators are being developed. One such activator, AUT00063, is being evaluated at the phase 2a stage by the London startup Autifony Therapeutics to treat hearing disorders. [Miceli et al., 2011 under CC BY 4.0 license.]
But a change in excitability may not be the only or even the most important consequence of SLACK down regulation, according to Kaczmarek. SLACK may act as an activity sensor, providing a direct link between neuronal firing and protein synthesis.
His teamhas previously shown that SLACK channel activity plays a role in synaptic development, through its ability to regulateactivity-dependent protein synthesis (Brown et al., 2010; Zhang et al., 2012). When you precipitate the channel from mammalian brain, it pulls down several messenger RNAs, he pointed out, and mutations that cause channel overactivity are associated with epilepsy (Barcia et al., 2012; Kim et al., 2015).
In fact, Kaczmarek added, it may not be the hyperexcitability of motor neurons that is toxic in ALS, but rather its proposed (but not yet tested) consequences on protein synthesis. A rapid change in the activity of these channels, as we saw here, is likely going to alter protein synthesis, and that can produce much longer-lasting effects, potentially more consistent with a late-onset disease.
This was an extremely elegant study, and an ingenious way to approach the issue of hyperexcitability, said Steve Vucic, who, in collaboration with University of Sydneys Matthew Kiernan in Australia helped identify these neuronal changes as an early sign of ALS in people with the disease. The goal now will be to see if this same pathway is affected in the mammalian models, or in human ALS iPS cells.
Brian Wainger agrees. The key questions, according to Wainger, are whether these findings hold up in mammalian models, and whether these findings can be generalized to other forms of the disease.
Searching for ALS-linked gene variants in SLACK or related ion channels might also provide insight into its relevance for the human disease, added Vucic.
Approaching the clinic
Hyperexcitability is clearly a clinical feature of many forms of familial and sporadic ALS, explains Wainger. Thats why it is attractive as a convergent mechanism for many forms of ALS. But one of the challenges is to determine to what extent an increase in firing is relevant for disease pathogenesis, rather than, as some argue, being a compensatory mechanism. Directly modulating excitability is one of the clearest ways of answering that question directly, he added.
If motor neuron hyperexcitabilitydoes hold up as a driver of disease, however, it may be a good target for therapy, according to Kaczmarek. I see this as very much a therapeutic possibility.
The reason is because opening up these potassium ion channels may help motor neurons in people with ALS return to their resting state and thereby, reduce hyperexcitability in the disease.
Finding magneto. Researchers are using transcranial magnetic stimulation to evaluate in part whether mexiletine and retigabine reduce hyperexcitability in people with the disease.[Image: NIH].
Kaczmareks team is now hoping to do just that by developing a SLACK activator. The project is ongoing.
In the meantime, clinicians are aiming to reduce hyperexcitability in people with ALS by repurposing existing medicines in hopes to treat the disease. Brian Wainger is leading an effort to determine whether the epilepsy drug retigabine may be helpful in ALS. The drug, identified by Wainger as a potential treatment while in the laboratory of Kevin Eggan, may help normalize the activity of motor neurons by opening up Kv7 potassium channels in people with the disease (see April 2016 news; ; Wainger et al., 2014).
Across the US, the University of Washingtons Michael Weiss is taking a different approach. He is evaluating whether mexiletine, a sodium channel blocker, may reduce hyperexcitability in people with the disease (see March 2016 news). Both strategies are currently at the phase 2 stage.
In a disease that has a selective neuronal vulnerability like ALS, says Wainger, I think it is likely that the electrophysiological properties of the neuron are going to be related to the degenerative nature of the disease. So normalizing those properties may have a good chance of being helpful.
References
Zhang Y, Ni W, Horwich AL, Kaczmarek LK. AnALS-associatedmutantSOD1rapidlysuppressesKCNT1 (Slack) Na+-activated K+ channels in Aplysia neurons. J Neurosci. 2017 Jan 24. pii: 3102-16. [PubMed]
Fritz E, Izaurieta P, Weiss A, Mir FR, Rojas P, Gonzalez D, Rojas F, Brown RH Jr, Madrid R, van Zundert B. MutantSOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability. J Neurophysiol. 2013 Jun;109(11):2803-14. 2013 Mar 13. [PubMed].
Hadzipasic M, Tahvildari B, Nagy M, Bian M, Horwich AL, McCormick DA. Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16883-8. [PubMed].
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van Zundert B, Peuscher MH, Hynynen M, Chen A, Neve RL, Brown RH Jr, Constantine-Paton M, Bellingham MC. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J Neurosci.2008 Oct 22;28(43):10864-74. [PubMed].
Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet. 2012 Nov;44(11):1255-9. [PubMed].
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Raoul C, Estvez AG, Nishimune H, Cleveland DW, deLapeyrire O, Henderson CE, Haase G, Pettmann B. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Neuron. 2002 Sep 12;35(6):1067-83. [PubMed].
LeeS, Shang Y, Redmond SA, Urisman A, Tang AA, Li KH, Burlingame AL, Pak RA, Jovii A, Gitler AD, Wang J, Gray NS, Seeley WW, Siddique T, Bigio EH,LeeVM, Trojanowski JQ, Chan JR, Huang EJ. Activation of HIPK2 Promotes ER Stress-Mediated Neurodegeneration in Amyotrophic Lateral Sclerosis. Neuron. 2016 Jul 6;91(1):41-55. [PubMed].
Song Y, Nagy M, Ni W, Tyagi NK, Fenton WA, Lpez-Girldez F, Overton JD, Horwich AL, Brady ST. Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5428-33. [PubMed].
Fujisawa T, Takahashi M, Tsukamoto Y, Yamaguchi N, Nakoji M, Endo M, Kodaira H, Hayashi Y, Nishitoh H, Naguro I, Homma K, Ichijo H. The ASK1-specific inhibitors K811 and K812 prolong survival in a mouse model of amyotrophic lateral sclerosis. Hum Mol Genet. 2016 Jan 15;25(2):245-53. [PubMed].
Brown MR, Kronengold J, Gazula VR, Chen Y, Strumbos JG, Sigworth FJ, Navaratnam D, Kaczmarek LK. Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nat Neurosci. 2010 Jul;13(7):819-21. [PubMed].
Zhang Y, Brown MR, Hyland C, Chen Y, Kronengold J, Fleming MR, Kohn AB, Moroz LL, Kaczmarek LK. Regulation of neuronal excitability by interaction of fragile X mental retardation protein with slack potassium channels. J Neurosci. 2012 Oct 31;32(44):15318-27. [PubMed].
Kim GE, Kronengold J, Barcia G, Quraishi IH, Martin HC, Blair E, Taylor JC, Dulac O, Colleaux L, Nabbout R, Kaczmarek LK. Human slack potassium channel mutations increase positive cooperativity between individual channels. Cell Rep. 2014 Dec 11;9(5):1661-72. [PubMed].
disease-als hyperexcitability mexiletine retigabine SOD1 topic-preclinical topic-researchmodels
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A key ion channel may SLACK off in ALS - ALS Research Forum
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February 20th, 2017
Hello, again, Dolly – The Economist
By daniellenierenberg
n}"Iu'.-[@$(~I)/NNbr. <~9Q/CN@ %G!kvPXrJMQ~Z"t~sMmLXpRzv78UUr * }RPN*cN[MPz%JTc6u|QuBvXE- 1GxNP03L4G`/Whsp =_:g[z_%z12"(}= AO^Elp|V.d~ M[(2j'='Jq&pT3zs)^3/Pa=-C.uo'8E7W[1&Vn s)2vL]VHC5u7dtfQ~{>V0 NNQNhu17*9&_^>5!EP5 mk`Az/<{Rp3Xm5@@3iJVD=d@[`^+UE+-;%%S_D'H@|n*&(@V{I 7f:^;7t4?7U|C Zc]>!we >'q6s>n@0aS~!I1Y6vV7J``4G$SGKjt?~ZEbvLWp"xETq [ ky/xH4iUB!X8L[q,5Z'cPL,>qKGV,cd72g]Xsn.Vh7%:6cwf,Y7njiF(E7: ssmY%XX.Ts>>v'p~@u]5b^; D(b{leDv M9:zT6R^3mk$^biv& \_%0L&.0Vd=Y,@=@=^vC!W!8Dy>E7_u_uAyy6xzGv[}{HkuTX$ I4nhlWtEt( Zhh]Ko8+[HS,NzHO INlnEI8EbH|C1MKoij[8iN]/]VMI~_pF8Y(nZhmp6R9/Kz^scV}tLj;3q/U="Ye?y%z%/yV)R*p7o[]ZU(YIohCiiwY6O2LAB]H+>o(4*d|+He_Wog6!Wu) mohEmB3NXlZI{J_E $xISAE/Rh43R$v!jmV R..k2naN4.b+zw6IrZ=HL.#>4K]RFxQ0|SPO#R.;'- See the original post here:
Hello, again, Dolly - The Economist
Market Players Developing iPS Cell Therapies
By Dr. Matthew Watson
While a number of companies have dabbled in this space, the following players are facilitating the development of iPS cell therapies: Cellular Dynamics International (CDI),Cynata Therapeutics, RIKEN, and Astellas (previously Ocata Therapeutics).
While each iPS cell therapy group is considered in detail below, Cellular Dynamics International (CDI) is featured first, because it dominates the iPSC industry. CDI also recently split into two business units, a Life Science Unit and a Therapeutics Unit, demonstrating a commercial strategy for its iPS cell therapy development.
Founded in 2004 and listed on NASDAQ in July 2013, Cellular Dynamics International (CDI) is headquartered in Madison, Wisconsin. The company is known for itsextremely robust patent portfolio containing more than 900 patents.
According to the company, CDI is the worlds largest producer of fully functional human cells derived from induced pluripotent stem (iPS) cells.[1] Their trademarked, iCell Cardiomyocytes, derived from iPSCs, are human cardiac cells used to aid drug discovery, improve the predictability of a drugs worth, and screen for toxicity. In addition, CDI provides: iCell Endothelial Cells for use in vascular-targeted drug discovery and tissue regeneration, iCell Hepatocytes, and iCell Neurons for pre-clinical drug discovery, toxicity testing, disease prediction, and cellular research.[2]
Induced pluripotent stem cells were first produced in 2006 from mouse cells and in 2007 from human cells, by Shinya Yamanaka at Kyoto University,[3] who also won the Nobel Prize in Medicine or Physiology for his work on iPSCs.[4] Yamanaka has ties toCellular Dynamics International as a member of the scientific advisory board of iPS Academia Japan. IPS Academia Japan was originally established to manage the patents and technology of Yamanakas work, and is now the distributor of several of Cellular Dynamics products, including iCell Neurons, iCell Cardiomyocytes, and iCell Endothelial Cells.[5]
Importantly, in 2010 Cellular Dynamics became the first foreign company to be granted rights to use Yamanakas iPSC patent portfolio.Not only has CDI licensed rights to Yamanakas patents, but it also has a license to use Otsu, Japan-based Takara Bios RetroNectin product, which it uses as a tool to produce its iCell and MyCell products.[6]
Furthermore, in February 2015, Cellular Dynamics International announcedit would be manufacturing cGMP HLA Superdonor stem cell lines that will support cellular therapy applications through genetic matching.[8] Currently, CDI has two HLA superdonor cell lines that provide a partial HLA match to approximately 19% of the population within the U.S., and it aims to expand its master stem cell bank by collecting more donor cell lines that will cover 95% of the U.S. population.[9]The HLA superdonor cell lines were manufactured using blood samples, and used to produce pluripotent iPSC lines, giving the cells the capacity to differentiate into nearly any cell within the human body.
On March 30, 2015, Fujifilm Holdings Corporation announced that it was acquiring CDI for $307 million, allowingCDI tocontinue to run its operations in Madison, Wisconsin, and Novato, California as a consolidated subsidiary of Fujifilm.[14] A key benefit of the merger is that CDIs technology platform enables the production of high-quality fully functioning iPSCs (and other human cells) on an industrial scale, while Fujifilm has developed highly-biocompatible recombinant peptidesthat can be shaped into a variety of forms for use as a cellular scaffoldin regenerative medicinewhen used in conjunction with CDIs products.[15]
Additionally, Fujifilm has been strengthening its presence in the regenerative medicine field over the past several years, including a recent A$4M equity stake in Cynata Therapeutics and anacquisition ofJapan Tissue Engineering Co. Ltd.in December 2014. Most commonly called J-TEC, Japan Tissue Engineering Co. Ltd. successfully launched the first two regenerative medicine products in the country of Japan.According toKaz Hirao, CEO of CDI, It is very important for CDI to get into the area of therapeutic products, and we can accelerate this by aligning it with strategic and technical resources present within J-TEC.
Kaz Hirao also states,For our Therapeutic businesses, we will aim to file investigational new drugs (INDs) with the U.S. FDA for the off-the-shelf iPSC-derived allogeneic therapeutic products. Currently, we are focusing on retinal diseases, heart disorders, Parkinsons disease, and cancers. For those four indicated areas, we would like to file several INDs within the next five years.
Finally, in September 2015, CDI againstrengthened its iPS cell therapycapacity by setting up a new venture, Opsis Therapeutics. Opsis is focused on discovering and developing novel medicines to treat retinal diseases and is apartnership with Dr. David Gamm, the pioneer of iPS cell-derived retinal differentiation and transplantation.
In summary, several key events indicate CDIs commitment to developing iPS cell therapeutics, including:
Australian stem cell company Cynata Therapeutics (ASX:CYP) is taking a unique approachby creating allogeneic iPSC derived mesenchyal stem cell (MSCs)on a commercial scale.Cynatas Cymerus technology utilizes iPSCs provided by Cellular Dynamics International, a Fujifilm company, as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-gradeMSCs.According to Cynatas Executive Chairman Stewart Washer who was interviewed by The Life Sciences Report, The Cymerus technology gets around the loss of potency with the unlimited iPS cellor induced pluripotent stem cellwhich is basically immortal.
OnJanuary 19, 2017, Fujifilm took anA$3.97 million (10%) strategic equity stakein Cynata, positioning the parties to collaborate on the further development and commercialisation of Cynatas lead Cymerus therapeutic MSC product CYP-001 for graft-versus-host disease (GvHD). (CYP-001 is the product designation unique to the GVHD indication). The Fujifilm partnership also includes potential future upfront and milestone payments in excess of A$60 million and double-digit royalties on CYP-001 product net sales for Cynata Therapeutics, as well as strategic relationship for potential future manufacture of CYP-001 and certain rights to other Cynata technology.
One of the key inventors of Cynatas technology is Igor Slukvin, MD, Ph.D., Scientific Founder of Cellular Dynamics International (CDI) and Cynata Therapeutics. Dr. Slukvin has released more than 70 publications about stem cell topics, including the landmark article in Cell describing the now patented Cymerus technique. Dr. Slukvins co-inventor is Dr. James Thomson, the first person to isolate an embryonic stem cell (ESC) and one of the first people to create a human induced pluripotent stem cell (hiPSC). Dr. James Thompson was theFounder of CDI in 2004.
There are three strategic connections between Cellular Dynamics International (CDI) and Cynata Therapeutics, which include:
Recently, Cynata received advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) that its Phase I clinical trial application has been approved, titledAn Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease. It will be the worlds first clinical trial involving a therapeutic product derived from allogeneic (unrelated to the patient) induced pluripotent stem cells (iPSCs).
Participants for Cynatas upcoming Phase I clinical trial will be adults who have undergone an allogeneic haematopoietic stem cell transplant (HSCT) to treat a haematological disorder and subsequently been diagnosed with steroid-resistant Grade II-IV GvHD.The primary objective of the trial is to assess safety and tolerability, while the secondary objective is to evaluate the efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.
Using Professor Yamankas Nobel Prize winning achievement of ethically uncontentious iPSCs and CDIs high quality iPSCs as source material, Cynata has achieved two world firsts:
Cynata has also released promising pre-clinical data in Asthma, Myocardial Infarction (Heart Attack), andCritical Limb Ischemia.
There are four key advantages of Cynatas proprietary Cymerus MSC manufacturing platform.Because the proprietary Cymerus technology allows nearly unlimited production of MSCs from a single iPSC donor, there is batch-to-batch uniformity. Utilizing a consistent starting material allows for a standardized cell manufacturing process and a consistent cell therapy product. Unlike other companies involved with MSC manufacturing, Cynata does not require a constant stream of new donors in order to source fresh stem cells for its cell manufacturing process, nor does it require the massive expansion of MSCs necessitated by reliance on freshly isolated donations.
Finally, Cynata has achieved a cost-savings advantage through its uniqueapproach to MSCmanufacturing. Its proprietary Cymerus technology addresses a critical shortcoming in existing methods of production of MSCs for therapeutic use, which is the ability to achieve economic manufacture at commercial scale.
On June 22, 2016, RIKEN announced that it is resuming its retinal induced pluripotent stem cell (iPSC) study in partnership with Kyoto University.
2013 was the first time in which clinical research involving transplant of iPSCs into humans was initiated, led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB)in Kobe, Japan. Dr. Takahashi and her team wereinvestigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration. Althoughthe trial was initiated in 2013 and production of iPSCs from patients began at that time, it was not until August of 2014 that the first patient, a Japanese woman, was implanted with retinal tissue generated using iPSCs derived from her own skin cells.
A team of three eye specialists, led by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, implanted a 1.3 by 3.0mm sheet of iPSC-derived retinal pigment epithelium cells into the patients retina.[196]Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them. Therefore, it is major news that theRIKEN Institute will now be resuming the worlds first clinical study involving the use of iPSC-derived cells in humans.
According to the Japan Times, this attempt at the clinical studywill involve allogeneic rather than autologous iPSC-derived cells for purposes of cost and time efficiency.Specifically,the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka. To learn about this announcement, view this article fromAsahi Shimbun, aTokyo- based newspaper.
In November 2015 Astellas Pharma announced it was acquiring Ocata Therapeutics for $379M. Ocata Therapeutics is a biotechnology company that specializes in the development of cellular therapies, using both adult and human embryonic stem cells to develop patient-specific therapies. The companys main laboratory and GMP facility is in Marlborough, Massachusetts, and its corporate offices are in Santa Monica, California.
When a number of private companies began to explore the possibility of using artificially re-manufactured iPSCs for therapeutic purposes, one such company that was ready to capitalize on the breakthrough technology was Ocata Therapeutics, at the time called Advanced Cell Technology. In 2010, the company announced that it had discovered several problematic issues while conducting experiments for the purpose of applying for U.S. Food and Drug Administration approval to use iPSCs in therapeutic applications. Concerns such as premature cell death, mutation into cancer cells, and low proliferation rates were some of the problems that surfaced. [17]
As a result, the company shifted its induced pluripotent stem cell approach to producingiPS cell-derived human platelets, as one of the benefits of a platelet-based product is that platelets do not contain nuclei, and therefore, cannot divide or carry genetic information. While the companys Induced Pluripotent Stem Cell-Derived Human Platelet Program received a great deal of media coverage in late 2012, including being awarded the December 2012 honor of being named one of the 10 Ideas that Will Shape the Yearby New Scientist Magazine,[178] unfortunately the company did not succeed in moving the concept through to clinical testing in 2013.
Nonetheless, Astellas is clearly continuing to develop Ocatas pluripotent stem cell technologies involving embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS cells). In a November 2015 presentation by Astellas President and CEO, Yoshihiko Hatanaka, he indicated that the company will aim to develop an Ophthalmic Disease Cell Therapy Franchise based around its embryonic stem cell (ESC) and induced pluripotent stem cell (iPS cell) technology. [19]
Footnotes [1] CellularDynamics.com (2014). About CDI. Available at: http://www.cellulardynamics.com/about/index.html. Web. 1 Apr. 2015. [2] Ibid. [3] Takahashi K, Yamanaka S (August 2006).Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell126(4): 66376. [4] 2012 Nobel Prize in Physiology or Medicine Press Release. Nobelprize.org. Nobel Media AB 2013. Web. 7 Feb 2014. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html. Web. 1 Apr. 2015. [5] Striklin, D (Jan 13, 2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet. Retrieved Feb 1, 2014 from, http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. [6] Striklin, D (2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet [Online]. Available at: http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. Web. 1 Apr. 2015. [7] Cellular Dynamics International (July 30, 2013). Cellular Dynamics International Announces Closing of Initial Public Offering [Press Release]. Retrieved from http://www.cellulardynamics.com/news/pr/2013_07_30.html. [8] Investors.cellulardynamics.com,. Cellular Dynamics Manufactures Cgmp HLA Superdonor Stem Cell Lines To Enable Cell Therapy With Genetic Matching (NASDAQ:ICEL). N.p., 2015. Web. 7 Mar. 2015. [9] Ibid. [10] Cellulardynamics.com,. Cellular Dynamics | Mycell Products. N.p., 2015. Web. 7 Mar. 2015. [11]Sirenko, O. et al. Multiparameter In Vitro Assessment Of Compound Effects On Cardiomyocyte Physiology Using Ipsc Cells.Journal of Biomolecular Screening18.1 (2012): 39-53. Web. 7 Mar. 2015. [12] Sciencedirect.com,. Prevention Of -Amyloid Induced Toxicity In Human Ips Cell-Derived Neurons By Inhibition Of Cyclin-Dependent Kinases And Associated Cell Cycle Events. N.p., 2015. Web. 7 Mar. 2015. [13] Sciencedirect.com,. HER2-Targeted Liposomal Doxorubicin Displays Enhanced Anti-Tumorigenic Effects Without Associated Cardiotoxicity. N.p., 2015. Web. 7 Mar. 2015. [14] Cellular Dynamics International, Inc. Fujifilm Holdings To Acquire Cellular Dynamics International, Inc.. GlobeNewswire News Room. N.p., 2015. Web. 7 Apr. 2015. [15] Ibid. [16]Cyranoski, David. Japanese Woman Is First Recipient Of Next-Generation Stem Cells. Nature (2014): n. pag. Web. 6 Mar. 2015. [17] Advanced Cell Technologies (Feb 11, 2011). Advanced Cell and Colleagues Report Therapeutic Cells Derived From iPS Cells Display Early Aging [Press Release]. Available at: http://www.advancedcell.com/news-and-media/press-releases/advanced-cell-and-colleagues-report-therapeutic-cells-derived-from-ips-cells-display-early-aging/. [18] Advanced Cell Technology (Dec 20, 2012). New Scientist Magazine Selects ACTs Induced Pluripotent Stem (iPS) Cell-Derived Human Platelet Program As One of 10 Ideas That Will Shape The Year [Press Release]. Available at: http://articles.latimes.com/2009/mar/06/science/sci-stemcell6. Web. 9 Apr. 2015. [19] Astellas Pharma (2015). Acquisition of Ocata Therapeutics New Step Forward in Ophthalmology with Cell Therapy Approach. Available at: https://www.astellas.com/en/corporate/news/pdf/151110_2_Eg.pdf. Web. 29 Jan. 2017.
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Market Players Developing iPS Cell Therapies
Regulators OK Clinical Trials Using Donor Stem Cells – The Scientist
By NEVAGiles23
The Scientist | Regulators OK Clinical Trials Using Donor Stem Cells The Scientist WIKIPEDIA, TMHLEEResearchers in Japan who have been developing a cell therapy for macular degeneration received support from health authorities this week (February 1) to begin a clinical trial using donor-derived induced pluripotent stem (IPS) cells ... |
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Regulators OK Clinical Trials Using Donor Stem Cells - The Scientist
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February 7th, 2017
What’s the benefit in making human-animal hybrids? – The Conversation AU
By raymumme
The red shows rat cells in the developing heart of a mouse embryo.
A team of scientists from the Salk Institute in the United States created a stir last week with the announcement that they had created hybrid human-pig foetuses.
The story was widely reported, although some outlets took a more hyperbolic or alarmed tone than others.
One might wonder why scientists are even creating human-animal hybrids often referred to as chimeras after the Greek mythological creature with features of lion, goat and snake.
The intention is not to create new and bizarre creatures. Chimeras are incredibly useful for understanding how animals grow and develop. They might one day be used to grow life-saving organs that can be transplanted into humans.
The chimeric pig foetuses produced by Juan Izpisua Belmonte, Jun Wu and their team at the Salk Institute were not allowed to develop to term, and contained human cells in multiple tissues.
The actual proportion of human cells in the chimeras was quite low and their presence appeared to interfere with development. Even so, the study represents a first step in a new avenue of stem cell research which has great promise. But it also raises serious ethical concerns.
A chimera is an organism containing cells from two or more individuals and they do occur in nature, albeit rarely.
Marmoset monkeys often display chimerism in their blood and other tissues as a result of transfer of cells between twins while still in the womb. Following a successful bone marrow transplantation to treat leukaemia, patients have cells in their bone marrow from the donor as well as themselves.
Chimeras can be generated artificially in the laboratory through combining the cells from early embryos of the same or different species. The creation of chimeric mice has been essential for research in developmental biology, genetics, physiology and pathology.
This has been made possible by advances in gene targeting in mouse embryonic stem cells, allowing scientists to alter the cells to express or silence certain genes. Along with the ability to use those cells in the development of chimeras, this has enabled researchers to produce animals that can be used to study how genes influence health and disease.
The pioneers of this technology are Oliver Smithies, Mario Cappechi and Martin Evans, who received a Nobel Prize in Physiology or Medicine in 2007 for their work.
More recently, researchers have become interested in investigating the ability of human pluripotent stem cells master cells obtained from human embryos or created in the laboratory from body cells, to contribute to the tissues of chimeric animals.
Human pluripotent stem cells can be grown indefinitely in the laboratory, and like their mouse counterparts, they can form all the tissues of the body.
Many researchers have now shown they can make functional human tissues of medical significance from human pluripotent cells, such as nerve, heart, liver and kidney cells.
Indeed, cellular therapeutics derived from human pluripotent stem cells are already in clinical trials for spinal cord injury, diabetes and macular degeneration.
However, since 2007 it has been clear that there is not one type of pluripotent stem cell. Rather, a range of different types of pluripotent stem cells have been generated in mice and humans using different techniques.
These cells appear to correspond to cells at different stages of embryonic development, and therefore are likely to have different properties, raising the question about which source of cells is best.
Creating a chimeras has long been the gold standard used by researchers to determine the potential of pluripotent stem cells. While used extensively in animal stem cell research, chimeric studies using human pluripotent stem cells have proved challenging as few human cells survive in human-animal chimeras.
Although the number of human cells in the chimera was low, the findings by the Salk Institute researchers provide a new avenue to address two important goals. The first is the possibility of creating humanised animals for use in biomedical research.
While it is already possible to produce mice with human blood, providing an invaluable insight into how our blood and immune system functions, these animals rely on the use of human fetal tissue and are difficult to make.
The use of pluripotent stem cells in human-animal chimeras might facilitate the efficient production of mice with human blood cells, or other tissues such as liver or heart, on a larger scale. This could greatly enhance our ability to study the development of diseases and to develop new drugs to treat them.
The second potential application of human-animal chimeras comes from some enticing studies performed in Japan in 2010. These studies were able to generate interspecies chimeras following the introduction of rat pluripotent stem cells into a mouse embryo that lacked a key gene for pancreas development.
As a result, the live born mice had a fully functional pancreas comprised entirely of rat cells. If a similar outcome could be achieved with human stem cells in a pig chimera, this would represent a new source of human organs for transplantation.
While scientifically achieving such goals remains a long way off, it is almost certain that progress in pluripotent stem cell biology will enable successful experimentation along these lines. But how much of this work is ethically acceptable, and where do the boundaries lie?
Many people condone the use of pigs for food or as a source of replacement heart valves. They might also be content to use pig embryos and foetuses as incubators to manufacture human pancreas or hearts for those waiting on the transplant list. But the use of human-monkey chimeras may be more contested.
Studies have shown that early cells of the central nervous system made from human embryonic stem cells can engraft and colonise the brain of a newborn mouse. This provides a proof of concept for possible cellular therapies.
But what if human cells were injected into monkey embryos? What would be the ethical and cognitive status of a newborn rhesus monkey whose brain consists of predominantly human nerves?
It may be possible to genetically engineer the cells so that human cells can effectively grow into replacement parts. But what safeguards do we need to ensure that the human cells dont also contribute to other organs of the host, such as the reproductive organs?
While the announcement of a human-pig chimera may have taken many by surprise, regulators and medical researchers well recognise that chimeric research may raise issues in addition to the those already posed by animal research.
However, rather than call for a blanket ban or restricting funding for this area of medical research, it requires careful case-by-case consideration by independent oversight committees fully aware of animal welfare considerations and recognising existing standards.
For example, The 2016 Guidelines for Clinical Research and Translation from the International Society for Stem Cell Research call for research where human gametes could be generated from human-animal chimeras to be prohibited, but supports research using human-animal chimeras conducted under appropriate review and oversight.
Chimeric research will and needs to continue. But equally scientists involved in this field need to continue to discuss and consider the implications of their research with the broader community. Chimeras can all too readily be dismissed as mythological monsters engendering fear.
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February 7th, 2017
Companies Developing Induced Pluripotent Stem Cell (iPS …
By daniellenierenberg
While a number of companies have dabbled in this space, the following players are facilitating the development of iPS cell therapies: Cellular Dynamics International (CDI), RIKEN, Cynata Therapeutics, and Astellas (previously Ocata Therapeutics).
While each iPS cell therapy group is considered in detail below, Cellular Dynamics International (CDI) is featured first, because it dominates the iPSC industry. CDI also recently split into two business units, a Life Science Unit and a Therapeutics Unit, demonstrating a commercial strategy for its iPS cell therapy development.
Cellular Dynamics International (CDI) is headquartered in Madison, Wisconsin, although it provides technical support and sales information from both the United States and Japan. CDI was founded in 2004 and listed on NASDAQ in July 2013. The company had global revenues of $16.7 million in 2014 and currently has 150+ employees. It also has an extremely robust patent portfolio containing more than 800 patents, of which 130 pertain to iPSCs.
According to the company, CDI is the worlds largest producer of fully functional human cells derived from induced pluripotent stem (iPS) cells.[1] Their trademarked, iCell Cardiomyocytes, derived from iPSCs, are human cardiac cells used to aid drug discovery, improve the predictability of a drugs worth, and screen for toxicity. In addition, CDI provides: iCell Endothelial Cells for use in vascular-targeted drug discovery and tissue regeneration, iCell Hepatocytes, and iCell Neurons for pre-clinical drug discovery, toxicity testing, disease prediction, and cellular research.[2] As such, CDIs main role with regard to iPCS therapy development is the production of industrial-scale, clinical-grade iPSCs.
As mentioned previously, induced pluripotent stem cells were first produced in 2006 from mouse cells and in 2007 from human cells, by Shinya Yamanaka at Kyoto University,[3] who also won the Nobel Prize in Medicine or Physiology for his work on iPSCs.[4] Yamanaka has ties toCellular Dynamics International as a member of the scientific advisory board of iPS Academia Japan.
IPS Academia Japan was originally established to manage the patents and technology of Yamanakas work, and is now the distributor of several of Cellular Dynamics products, including iCell Neurons, iCell Cardiomyocytes, and iCell Endothelial Cells.[5] Importantly, in 2010 Cellular Dynamics became the first foreign company to be granted rights to use Yamanakas iPSC patent portfolio.Not only has CDI licensed rights to Yamanakas patents, but it also has a license to use Otsu, Japan-based Takara Bios RetroNectin product, which it uses as a tool to produce its iCell and MyCell products.[6] Through its licenses and intellectual property, CDI currently uses induced pluripotent stem cells to produce human heart cells (cardiomyocytes), brain cells (neurons), blood vessel cells (endothelial cells), and liver cells (hepatocytes), manufacturing them in high quantity, quality, and purity.
These human cells produced by the company are used for both in vitro and in vivo applications that range from basic and applied research to drug discovery research that includes target identification and validation, toxicity testing, safety and efficacy testing, and more. As such, CDI has emerged as a global leader with the ability to generate iPSCs that have the potential to be used for a wide range of research and possibly therapeutic purposes.
In a landmark event with the iPSC market, the company had an initial public offering (IPO) in July of 2013, in which it sold 38,460,000 shares of common stock to the public at $12.00 per share, to raise proceeds of approximately $43 million.[7] This event secured the companys position as the global leader in producing high-quality human iPSCs and differentiated cells in industrial quantities.
In addition, in March of 2013, Celullar Dynamics International and the Coriell Institute for Medical Research announced receiving multi-million dollars grants from the California Institute for Regenerative Medicine (CIRM) for the creation of iPSC lines from 3,000 healthy and diseased donors, a result that will create the worlds largest human iPSC bank.
Not surprisingly, Cellular Dynamics International has continued its innovation, announcing in February of 2015 that it would be manufacturing cGMP HLA Superdonor stem cell lines that will support cellular therapy applications through genetic matching.[8] Currently, CDI has two HLA superdonor cell lines that provide a partial HLA match to approximately 19% of the population within the U.S., and it aims to expand its master stem cell bank by collecting more donor cell lines that will cover 95% of the U.S. population.[9]
The HLA superdonor cell lines were manufactured using blood samples, and used to produce pluripotent iPSC lines, giving the cells the capacity to differentiate into nearly any cell within the human body.
CDI also leads the iPSC market in terms of supporting drug development and discovery. For example, CDIs MyCell products are created using custom iPSC reprogramming and differentiation methods, thereby providing biologically relevant human cells from patients with unique disease-associated genotypes and phenotypes.[10] The companys iCell and MyCell cells can also be adapted to screening platforms and are matched to function with common readout technologies.[11] CDIs products are also used for high-throughput screening,[12] and have been used as supporting data for Investigational New Drug (IND) applications submitted to the Federal Drug Administration (FDA).[13]
On March 30, 2015, Fujifilm Holdings Corporation announced that it was acquiring CDI, in which Fujifilm will acquire CDI through all-cash offer followed by a second step merger. Specifically, Fujifilm will acquire all issued and outstanding shares of CDIs common stock for $16.5 per share or approximately $ 307 million, after which CDI will continue to run its operations in Madison, Wisconsin, and Novato, California as a consolidated subsidiary of Fujifilm.[14]
CDIs technology platform enables the production of high-quality fully functioning iPSCs (and other human cells) on an industrial scale, while Fujifilm has developed highly-biocompatible recombinant peptidesthat can be shaped into a variety of forms for use as a cellular scaffoldin regenerative medicinewhen used in conjunction with CDIs products.[15] Fujifilm has been strengthening its presence in the regenerative medicine field over several years, including by acquiring a majority of shares of Japan Tissue Engineering Co. in December 2014, so while the acquisition was unexpected, it as not fully suprising.
In summary, the acquisition of CDI will allow Fujifilm to gaindominance in the areaof iPS cell-based drug discovery services and will position it to strategically combine CDIs iPS cell technologywithFujifilms expertise in material science and engineering systems, creating a powerhouse within the iPSC market. It is yet to be seen whether Fujifilm will try to commercialize CDIs iPS cell production technologies by making the cells available for clinical use or whether they will choose to focus their attention on iPS cell-based drug discovery services.
In November 2015 Astellas Pharma announced it was acquiring Ocata Therapeutics for $379M. Ocata Therapeutics is a biotechnology company that specializes in the development of cellular therapies, using both adult and human embryonic stem cells to develop patient-specific therapies. The companys main laboratory and GMP facility is in Marlborough, Massachusetts, and its corporate offices are in Santa Monica, California.
When a number of private companies began to explore the possibility of using artificially re-manufactured iPSCs for therapeutic purposes, one such company that was ready to capitalize on the breakthrough technology was Ocata Therapeutics (at the time called Advanced Cell Technology or ACT). In 2010, the company announced that it had discovered several problematic issues while conducting experiments for the purpose of applying for U.S. Food and Drug Administration approval to use iPSCs in therapeutic applications. Concerns such as premature cell death, mutation into cancer cells, and low proliferation rates were some of the problems that surfaced. [16]
As a result, the company has since shifted its induced pluripotent stem cell approach to producingiPS cell-derived human platelets, as one of the benefits of a platelet-based product is that platelets do not contain nuclei, and therefore, cannot divide or carry genetic information. Although nothing is completely safe, iPS cell-derived platelets are likely to be much safer than other iPSC therapies, in which uncontrolled proliferation is a major concern.
While the companys Induced Pluripotent Stem Cell-Derived Human Platelet Program received a great deal of media coverage in late 2012, including being awarded the December 2012 honor of being named one of the 10 Ideas that Will Shape the Yearby New Scientist Magazine,[17] unfortunately the company did not succeed in moving the concept through to clinical testing in 2013.
Nonetheless, in a November 2015 presentation by Astellas President and CEO, Yoshihiko Hatanaka, he indicated that the company will aim to develop an Ophthalmic Disease Cell Therapy Franchise based around its embryonic stem cells (ESCs) and induced pluripotent stem cell (iPS cells) technology. [18]
On June 22, 2016, RIKEN announced that it is resuming its retinal induced pluripotent stem cell (iPSC) study in partnership with Kyoto University.
2013 was the first time in which clinical research involving transplant of iPSCs into humans was initiated, led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB)in Kobe, Japan. Dr. Takahashi and her team wereinvestigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration. Althoughthe trial was initiated in 2013 and production of iPSCs from patients began at that time, it was not until August of 2014 that the first patient, a Japanese woman, was implanted with retinal tissue generated using iPSCs derived from her own skin cells.
A team of three eye specialists, led by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, implanted a 1.3 by 3.0mm sheet of iPSC-derived retinal pigment epithelium cells into the patients retina.[19]Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them. Therefore, it is major news that theRIKEN Institute will now be resuming the worlds first clinical study involving the use of iPSC-derived cells in humans.
According to the Japan Times, this attempt at the clinical studywill involve allogeneic rather than autologous iPSC-derived cells for purposes of cost and time efficiency.Specifically,the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka. To learn about this announcement, view this article fromAsahi Shimbun, aTokyo- based newspaper.
Australian stem cell company Cynata Therapeutics (ASX:CYP) is taking a unique approach. It is creating allogeneic iPS cell derived mesenchyal stem cell (MSCs).Cynatas Cymerus technology utilizes iPSCs originating from an adult donor as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-gradeMSCs.
One of the key inventors of the approach is Igor Slukvin, who has released more than 70 publications about stem cell topics, including the landmark article in Cell describing the now patented Cymerus technique. Dr. Slukvins co-inventor is James Thomson, the first person to isolate an embryonic stem cell (ESC) and one of the first people to create a human-induced, pluripotent stem cell (hiPSC).
Recently, Cynata received advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) that its Phase I clinical trial application has been approved, titledAn Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease. It will be the worlds first clinical trial involving a therapeutic product derived from allogeneic (unrelated to the patient) induced pluripotent stem cells (iPSCs).
Participants for Cynatas upcoming Phase I clinical trial will be adults who have undergone an allogeneic haematopoietic stem cell transplant (HSCT) to treat a haematological disorder and subsequently been diagnosed with steroid-resistant Grade II-IV GvHD.The primary objective of the trial is to assess safety and tolerability, while the secondary objective is to evaluate the efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.
There are four key advantages of Cynatas proprietary Cymerus MSC manufacturing platform, as described below.
Unlimited Quantities Cynatas Cymerus technology utilizes iPSCs originating from an adult donor as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-gradeMSCs. According to Cynatas Executive Chairman Stewart Washer who was recently interviewed by The Life Sciences Report, The Cymerus technology gets around the loss of potency with the unlimited iPS cellor induced pluripotent stem cellwhich is basically immortal.
Uniform Batches Because the proprietary Cymerus technology allows nearly unlimited production of MSCs from a single iPSC donor, there is batch-to-batch uniformity. Utilizing a consistent starting material allows for a standardized cell manufacturing process and a consistent cell therapy product.
Single Donor As described previously, Cynatas Cymerus technology creates iPSC-derived mesenchymoangioblasts (MCAs), which are differentiated into MSCs. Unlike other companies involved with MSC manufacturing, Cynata does not require a constant stream of new donors in order to source fresh stem cells for its cell manufacturing process, nor does it require the massive expansion of MSCs necessitated by reliance on freshly isolated donations.
Economic Manufacture at Commercial Scale (Low Cost) Finally, Cynata has achieved a cost-savings advantage through its uniqueapproach to MSCmanufacturing. Its proprietary Cymerus technology addresses a critical shortcoming in existing methods of production of MSCs for therapeutic use, which is the ability to achieve economic manufacture at commercial scale.
Footnotes [1] CellularDynamics.com (2014). About CDI. Available at: http://www.cellulardynamics.com/about/index.html. Web. 1 Apr. 2015. [2] Ibid. [3] Takahashi K, Yamanaka S (August 2006).Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell126(4): 66376. [4] 2012 Nobel Prize in Physiology or Medicine Press Release. Nobelprize.org. Nobel Media AB 2013. Web. 7 Feb 2014. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html. Web. 1 Apr. 2015. [5] Striklin, D (Jan 13, 2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet. Retrieved Feb 1, 2014 from, http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. [6] Striklin, D (2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet [Online]. Available at: http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. Web. 1 Apr. 2015. [7] Cellular Dynamics International (July 30, 2013). Cellular Dynamics International Announces Closing of Initial Public Offering [Press Release]. Retrieved from http://www.cellulardynamics.com/news/pr/2013_07_30.html. [8] Investors.cellulardynamics.com,. Cellular Dynamics Manufactures Cgmp HLA Superdonor Stem Cell Lines To Enable Cell Therapy With Genetic Matching (NASDAQ:ICEL). N.p., 2015. Web. 7 Mar. 2015. [9] Ibid. [10] Cellulardynamics.com,. Cellular Dynamics | Mycell Products. N.p., 2015. Web. 7 Mar. 2015. [11]Sirenko, O. et al. Multiparameter In Vitro Assessment Of Compound Effects On Cardiomyocyte Physiology Using Ipsc Cells.Journal of Biomolecular Screening18.1 (2012): 39-53. Web. 7 Mar. 2015. [12] Sciencedirect.com,. Prevention Of -Amyloid Induced Toxicity In Human Ips Cell-Derived Neurons By Inhibition Of Cyclin-Dependent Kinases And Associated Cell Cycle Events. N.p., 2015. Web. 7 Mar. 2015. [13] Sciencedirect.com,. HER2-Targeted Liposomal Doxorubicin Displays Enhanced Anti-Tumorigenic Effects Without Associated Cardiotoxicity. N.p., 2015. Web. 7 Mar. 2015. [14] Cellular Dynamics International, Inc. Fujifilm Holdings To Acquire Cellular Dynamics International, Inc.. GlobeNewswire News Room. N.p., 2015. Web. 7 Apr. 2015. [15] Ibid. [16] Advanced Cell Technologies (Feb 11, 2011). Advanced Cell and Colleagues Report Therapeutic Cells Derived From iPS Cells Display Early Aging [Press Release]. Available at: http://www.advancedcell.com/news-and-media/press-releases/advanced-cell-and-colleagues-report-therapeutic-cells-derived-from-ips-cells-display-early-aging/. [17] Advanced Cell Technology (Dec 20, 2012). New Scientist Magazine Selects ACTs Induced Pluripotent Stem (iPS) Cell-Derived Human Platelet Program As One of 10 Ideas That Will Shape The Year [Press Release]. Available at: http://articles.latimes.com/2009/mar/06/science/sci-stemcell6. Web. 9 Apr. 2015. [18] Astellas Pharma (2015). Acquisition of Ocata Therapeutics New Step Forward in Ophthalmology with Cell Therapy Approach. Available at: https://www.astellas.com/en/corporate/news/pdf/151110_2_Eg.pdf. Web. 29 Jan. 2017. [19]Cyranoski, David. Japanese Woman Is First Recipient Of Next-Generation Stem Cells. Nature (2014): n. pag. Web. 6 Mar. 2015.
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January 30th, 2017
Cell Science & Therapy – omicsonline.org
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The Journal of Cell Science & Therapy is an Open Access, peer-reviewed, academic journal with a wide range of fields within the discipline creates a platform for the authors to publish their comprehensive and most reliable source of information on the discoveries and current developments in the mode of original articles, review articles, case reports, short communications, etc, making them freely available through online without any restrictions or any other subscriptions to researchers worldwide.
The journal is using Editorial Manager System for quality in peer review process. Editorial Manager is an online manuscript submission, review and tracking systems. Review processing is performed by the editorial board members of Journal of Cell Science & Therapy or outside experts; at least two independent reviewers approval followed by editor approval is required for acceptance of any citable manuscript. Authors may submit manuscripts and track their progress through the system, hopefully to publication. Reviewers can download manuscripts and submit their opinions to the editor. Editors can manage the whole submission/review/revise/publish process.
Journal of Cell Science & Therapy is a peer reviewed scientific journal known for rapid dissemination of high-quality research. This Cell Science journal with highest impact factor offers an Open Access platform to the authors in academia and industry to publish their novel research. It serves the International Scientific Community with its standard research publications.
Cells are small compartments that hold the biological equipment necessary to keep an organism alive and successful. Living things may be unicellular or multicellular such as a human being. According to cell theory, cells are the fundamental unit of structure and function in all living organisms and come from preexisting cells, and that all cells contain the hereditary information necessary for regulating cell functions and for transmitting information to the next generation of cells.
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The cytokines produced by expression from suitable cloning vectors containing the desired cytokine gene, can be expressed in yeast (Saccharomyces cerevisiae expression system), bacteria (Escherichia coli expression system), mammalian cells (BHK, CHO, COS, Namalwa), or insect cell systems. Cytokines are designed for demanding applications such as cell culture, differentiation studies, and functional assays mainly in the fields of immunology, neurology, and stem cell research.
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Hematology is the investigation of blood, the blood-framing organs, and blood diseases in which the specialists deal with the diagnosis, treatment and overall management of people with blood disorders ranging from anemia to blood cancer. Some of the diseases treated by haematologists include Iron deficiency anaemia, Sickle cell anemia, Polycythemia or excess production of red blood cells, Myelofibrosis, Leukemia, hemophilia, myelodysplastic syndromes, Malignant lymphomas, Blood transfusion and bone marrow stem cell transplantation
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Cell biology (cytology) is a branch of biology that studies cells their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division, death and cell function. Research in cell biology is closely related to genetics, biochemistry, molecular biology, immunology, and developmental biology.
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A hair follicle is part of the skin that grows hair by packing old cells together. Attached to the follicle is a sebaceous gland, a tiny sebum-producing gland found everywhere except on the palms, lips and soles of the feet. The follicle cells that extrude hairs from just below the surface of the skin are simply too hard to bring back to life, and even preventative therapies didnt seem to be able to do much to keep them alive. But research on inducing stem cells to grow into follicle cells could change that forever.
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Mesenchymal stem cells (MSCs), the major stem cells for cell therapy. From animal models to clinical trials, MSCs have afforded promise in the treatment of numerous diseases, mainly tissue injury and immune disorders. Cell sources for MSC administration in clinical applications, and provide an overview of mechanisms that are significant in MSC-mediated therapies. Although MSCs for cell therapy have been shown to be safe and effective, there are still challenges that need to be tackled before their wide application in the clinical research field.
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Ovation Cell Therapy Hair Treatment nourishes hair and scalp with proteins and amino acids that bind and absorb into the hair shaft for hair that is noticeably thicker, stronger, and longer. The Ovation Cell Therapy is the heart of the system and is often where the system draws occasional criticism for its claims to accelerate hair growth and reduce breakage and hair loss.
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The external effects of degenerative processes inside the body which manifest especially in the face, hands, dcollet, and by hair loss are also psychically stressful. There are promising therapeutic approaches with stem cells and growth factors for both skin regeneration and hair growth regeneration. To dispense with hair transplants and surgical procedures such as facelifts and eyelid correction, in which the skin is pulled back and the excess tissue is excised. To treat the root cause and restore lost volume in a tissue-conserving, natural manner and regenerate both the subcutaneous tissue and the skin.
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Somatic cell therapy is viewed as a more conservative, safer approach because it affects only the targeted cells in the patient, and is not passed on to future generations. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy.
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Rejuvenation and regeneration are two key processes that define cell therapy. Cellular Therapy is a form of non-toxic, holistic medicine in which the entire organism is being treated. Cellular Therapies are an integral part of complimentary treatment regimens. They are extremely versatile and can be used for a wide range of disorders.
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Dendritic cells (DCs) cells are the most potent antigen-producing cells, represent unique antigen-producing cells capable of sensitizing T cells to both new and recall antigens. Dendritic Cell Vaccines, or Dendritic cell therapy, is another Alternative Cancer Therapy or newly emerging and potent form of immune therapy used to treat cancer.
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The cells are most commonly immune-derived, with the goal of transferring immune functionality and characteristics along with the cells. Transferring autologous cells minimizes GVHD issues. The adaptive transfer of autologous tumor infiltrating lymphocytes (TIL) or genetically re-directed peripheral blood mononuclear cells has been used to treat patients with advanced solid tumors, including melanoma and colorectal carcinoma, as well as patients with CD19-expressing hematologic malignancies. As of 2015 the technique had expanded to treat cervical cancer, lymphoma, leukemia, bile duct cancer and neuroblastoma.
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The ability to convert one cell type into another has caused great excitement in the stem cell field. iPS Reprogramming and transdifferentiation are the two approaches which makes cells in to another type of cells. In iPS procedure, it make possible to convert essentially any cell type in the body back into pluripotent stem cells that are almost identical to embryonic stem cells. And another approach uses transcription factors to convert a given cell type directly into another specialized cell type, without first forcing the cells to go back to a pluripotent state.
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Advance Cell & Gene Thearpy practical, experienced guidance in development, GMP/GTP manufacturing, and regulatory compliance, as well as comprehensive scientific and technical strategic analysis of business opportunities in cell therapy, gene therapy and tissue therapies.
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Immunotherapy involves engineering patients own immune cells to recognize and attack their tumors. And although this approach, called adoptive cell transfer (ACT), has been restricted to small clinical trials so far, treatments using these engineered immune cells have generated some remarkable responses in patients with advanced cancer. .Adoptive T cell therapy for cancer is a form of transfusion therapy consisting of the infusion of various mature T cell subsets with the goal of eliminating a tumor and preventing its recurrence.
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Commercialization of the first cell-based therapeutics, including cartilage repair products; tissue-engineered skin; and the first personalized, cellular immunotherapy for cancer. Production, storage, and delivery of living cell-based pharmaceuticals presents several unique challenges. Novel, innovative technologies and strategies will be required to bring cell therapies to commercial success.
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Cellular therapy products include cellular immunotherapies, and other types of both autologous and allogeneic cells for certain therapeutic indications, including adult and embryonic stem cells. Human gene therapy refers to products that introduce genetic material into a persons DNA to replace faulty or missing genetic material, thus treating a disease or abnormal medical condition.
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Journal of Cell Science and Therapy is associated with our international conference "6th World Congrss on Cell & Stem Cell Research" during Feb 29- March 2, 2016 Philadelphia, USA with a theme "Novel Therapies in Cell Science and Stem Cell Research. Stem Cell Therapy-2016 will encompass recent researches and findings in stem cell technologies, stem cell therapies and transplantations, current understanding of cell plasticity in cancer and other advancements in stem cell research and cell science.
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