The Scientist | Antibody Therapy Targets Cancer Stem Cells: Study The Scientist Carla Kim, an expert in stem cells, cancer, and lung biology at Harvard Medical School who was not involved in the study, acknowledged the importance of the research. One nice thing about this is that they're studying EGFR-mutant tumors, she said ... |
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Antibody Therapy Targets Cancer Stem Cells: Study - The Scientist
The most exciting aspect of our findings is that no matter what kind of brain tumor we tested it against, this treatment worked really well in the animal models, said Cheshier, who is also a pediatric neurosurgeon at Lucile Packard Childrens Hospital Stanford. In mice that had been implanted with both normal human brain cells and human brain cancer cells, there was no toxicity to normal human cells but very, very active tumor-killing in vivo, he said.
Given the encouraging results of the new study and the ongoing research on anti-CD47 antibodies in adults, the antibodies are expected to reach clinical trials in children with brain cancer in one to two years, he added.
The anti-CD47 antibodies help the immune system to detect an important difference between cancerous and healthy cells: Cancer cells make eat me signals that are displayed on their cell surfaces, while healthy cells do not. However, cancer cells hide these eat me signals by producing large quantities of CD47, a dont eat me protein that is found on the surface of both healthy and malignant cells. When CD47 is blocked by antibodies, immune cells called macrophages can detect the cancer cells eat me signals. Macrophages then selectively target, engulf and destroy the cancer cells without harming healthy cells, because normal cells lack the eat me signals.
The Stanford team conducted a long series of experiments using different combinations of tumor cells and healthy cells in culture, as well as in various mouse models in which human brain cancer cells had been implanted in mice. Highlights of their experiments included the following:
The anti-CD47 antibodies did not completely eliminate all tumors, suggesting that the antibodies may not be able to completely penetrate large tumors, the researchers noted.
To maximize their effects, the antibodies will likely need to be combined with other forms of cancer treatment, a concept the researchers plan to investigate further, Cheshier said. In the future, patients may receive combinations of immune therapies and lower doses of standard cancer treatments, he said, adding, The question is: Can we wisely combine immune therapies and other approaches to make cancer treatment more efficacious and less toxic?
Anti-CD47 antibodies also may have an advantage over other immunotherapies in that they activate macrophages, which completely engulf and eat cancer cells, Cheshier noted. In many forms of immunotherapy, the cells you target die and spill their contents, which can cause dysregulated immune responses, he said. Anti-CD47 antibodies may produce fewer such side effects, though the idea remains to be tested.
Other Stanford co-authors of the paper are medical students Abdullah Feroze, Rogelio Esparza and Michael Zhang; postdoctoral scholars Suzana Kahn, PhD, Anne Volkmer, MD and Stephen Willingham, PhD; research assistants Anitha Ponnuswami, Theresa Storm, Cyndhavi Narayanan and Pauline Chu; senior research associate Jie Liu, MD, PhD; undergraduate research associate Chase Richard; Aaron McCarthy, a former life sciences research professional and animal colony manager; Patricia Lovelace, research and development engineer; Simone Schubert, life science researcher; visiting scholar Gregor Hutter, MD, PhD; Griffith Harsh, MD, professor of neurosurgery; Michelle Monje, MD, PhD, assistant professor of neurology; Yoon-Jae Cho, MD, a former assistant professor of neurology and neurological sciences; Ravi Majeti, MD, PhD, associate professor of medicine; senior scientist Jens Volkmer, MD; Paul Fisher, MD, professor of pediatrics; Gerald Grant, MD, associate professor of neurosurgery; Gary Steinberg, MD, PhD, professor of neurosurgery; Hannes Vogel, MD, professor of pathology and of pediatrics; and Michael Edwards, MD, professor of neurosurgery.
Cheshier, Monje, Majeti, Fisher, Grant and Edwards are members of Stanfords Child Health Research Institute. Cheshier, Weissman, Harsh, Monje, Majeti, Fisher, Grant, Vogel and Edwards are members of the Stanford Cancer Institute. Weissman is the director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and of the Ludwig Center for Cancer Stem Cell Research and Medicineat Stanford.
Scientists from SickKids, the Hospital for Sick Children in Toronto; University Hospital, Dusseldorf; and Johns Hopkins University also contributed to the study.
The study was funded by National Institute of Neurological Disorders and Stroke (grant NINDSK08NS070926); the National Cancer Institute (grant P30CA006973); the California Institute for Regenerative Medicine; the Price Family Charitable Fund; the Center for Childrens Brain Tumors at Stanford; St. Baldricks Foundation; the American Brain Tumor Foundation; the Seibel Stem Cell Institute; the Pew Charitable Trusts; the Dr. Mildred-Scheel Foundation/German Cancer Aid; the German Research Foundation; the McKenna Claire Foundation; the Matthew Larson Foundation; Alexs Lemonade Stand Foundation; The Cure Starts Now; the Lyla Nsouli Foundation; the Dylan Jewett, Connor Johnson, Zoey Ganesh, Dylan Frick, Abigail Jensen, Wayland Villars and Jennifer Kranz memorial funds; the Virginia and D. K. Ludwig Fund for Cancer Research; the Lucile Packard Foundation for Childrens Health; the National Institutes of Health (grant UL1TR001085); the Tashia and John Morgridge Endowed Pediatric Faculty Scholar and Fellowships Awards; and the Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases. The study was also funded by gifts from George Landegger; Rider and Victoria McDowell; Charles Comey and Judith Huang; and Colin and Jenna Fisher.
Stanfords Department of Neurology & Neurological Sciences also supported the work.
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Antibody fights pediatric brain tumors in preclinical testing | News ... - Stanford Medical Center Report
Inside a bony structure that spirals like a snail shell in a humans inner ear, roughly 15,000 hair cells receive, translate, and then ship sound signals to the brain. Damage to these cells from excessive noise, chronic infections, antibiotics, certain drugs, or the simple passing of time can lead to irreparable hearing loss.
Harvard Stem Cell Institute (HSCI) researchers at Brigham and Womens Hospital (BWH) and Massachusetts Eye and Ear Infirmary and colleagues from Massachusetts Institute of Technology (MIT) have developed an approach to replace damaged sound-sensing hair cells, which eventually may lead to therapies for people who live with disabling hearing loss.
In a recent Cell Reports study, the researchers identified a small molecule cocktail that increased the population of cells responsible for generating hair cells in the inner ear. Unlike hair on the human head, the hair cells lining that bony structure, called the cochlea, do not regenerate.
HSCI principal faculty Jeff Karp, HSCI affiliate faculty Albert Edge, and MITs Robert Langer were co-corresponding authors of the study. Will McLean, a postdoctoral fellow in the Edge lab, and Xiaolei Yin, an instructor in medicine at BWH, were co-first authors.
In 2012, Edge and colleagues identified a population of stem cells, characterized by an Lgr5+ marker, which scientists could turn into hair cells in a dish. A year later, Edge had converted the resident population of these cells in mice into hair cells, though the ability to restore hearing using this approach has been limited.
The problem is the cochlea is so small and there are so few cells that it creates a bottleneck limiting the number and types of experiments researchers could perform, said Edge, director of the Tillotson Cell Biology Unit at Mass. Eye and Ear and a professor of otolaryngology at Harvard Medical School (HMS).
However, by exposing Lgr5+ cells isolated from the cochlea of mice to the small molecule cocktail, the researchers were able to create a 2,000-fold increase in the number of stem cells.
Those molecules were a key to unlocking this regenerative capability, said Karp, who is also a bioengineer at BWH and an associate professor of medicine at HMS.
Inspired by creatures with significant regenerative potential, including lizards and sharks, Karps lab initially turned to one of the bodys most highly regenerative tissues, the gastrointestinal lining, which completely replaces itself every four to five days. Central to this process is the paneth cell, neighbor to the intestinal stem cells that are responsible for generating all mature cell types in the intestine. The paneth cells effectively tell the stem cells, also characterized by their Lgr5+ markers, when to turn on and off.
Karp and his colleagues at MIT looked at the basic biology of the ties between paneth cells and intestinal stem cells and identified small molecules that could communicate directly with and control the Lgr5+ stem cells.
While we were developing the approach for the intestinal cells, we demonstrated it also worked in several other tissues with the Lgr5+ stem cells and progenitors, including the inner ear, Karp said.
When the researchers coupled the cocktail with established differentiation protocols, they were able to generate large quantities of functional hair cells in a petri dish. Using protocols from the Edge lab, the researchers then thoroughly characterized the differentiated cells to demonstrate they were functional hair cells. Researchers tested the cocktail on newborn mice, adult mice, non-human primates, and cells from a human cochlea.
We can now use these cells for drug screening as well as genetic analysis, Edge said. Our lab is using the cells to better understand the pathways for expansion and differentiation of the cells.
Additionally, the small molecule cocktail may also be turned into a therapeutic treatment. Karp has co-founded Frequency Therapeutics, which plans to use insights from these studies to develop treatments for hearing loss. The team hopes to begin human clinical testing within 18 months.
Not only is it a potential therapeutic that could be relevant for the restoration of hearing, but this approach is a platform, said Karp. The concept of targeting stem cells and progenitor cells in the body with small molecules to promote tissue regeneration can be applied to many tissues and organ systems.
By Alvin Powell, Harvard Staff Writer | March 15, 2017
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Progress in treating hearing loss - Harvard Gazette
A breakthrough study looking at how the brain repairs itself could revolutionize treatments for multiple sclerosis. The research, performed on mice and tissue cultures, reveals for the first time that a type of cell involved in immune control also releases a protein that triggers regrowth of myelin.
The international study - led by Queen's University Belfast in Northern Ireland, United Kingdom - is published in the journal Nature Neuroscience.
Senior author Dr. Denise Fitzgerald - of the University's Wellcome-Wolfson Institute for Experimental Medicine - describes the findings as "an important step forward in understanding how the brain and spinal cord is naturally repaired."
Worldwide, more than 2.3 million people are affected by multiple sclerosis (MS) - a disease in which the immune system mistakenly attacks the tissue of the central nervous system, which consists of the brain, spinal cord, and optic nerves.
In MS, the immune system attacks and destroys myelin - the fatty, protective sheath that surrounds and insulates nerve fibers.
As the myelin damage increases, it disrupts the signals that travel to and from the brain along the affected nerve fibers. This results in a range of symptoms that include impaired mobility, extreme fatigue, vision problems, pain, and altered sensation.
Although anyone can develop MS, it is the most common neurological disease in young adults and it affects two to three times more women than men.
Fast facts about MS
Learn more about MS
There is no evidence that MS is hereditary, but it is thought that genes play a role, as well as certain environmental factors such as low vitamin D and smoking tobacco.
There is currently no cure for MS, although some approved drugs appear to reduce frequency of relapses and delay disease progression to some extent.
The researchers are excited about their discovery because it takes treatment research into the area of reversing myelin damage.
Dr. Fitzgerald has a personal as well as a professional interest in MS - when she was 21, she had to learn to walk again after experiencing a similar condition called transverse myelitis.
The study concerns a type of immune cell called T cells, which, in cases of MS, are known to cross over from the bloodstream into the central nervous system.
Dr. Fitzgerald and colleagues discovered that a subtype of T cells called regulatory T cells - which are already known to be involved in regulating the immune system - also have a role in promoting myelin regrowth.
The regulatory T cells promote myelin regrowth through their effect on oligodendrocytes - the cells that make myelin. The process of myelin regrowth requires oligodendrocyte progenitor cells to mature into oligodendrocyte cells.
The researchers found that regulatory T cells release a protein that stimulates the differentiation of the progenitor cells into mature oligodendrocytes.
They showed that mice deficient in regulatory T cells showed substantially impaired myelin regeneration, which was restored when they transferred regulatory T cells into the mice.
Using cultured brain tissue, the researchers also showed that regulatory T cells "accelerated developmental myelination and remyelination, even in the absence of overt inflammation."
They conclude that their findings reveal a regenerative function for regulatory T cells that is separate from their role in regulating the immune response.
"This exciting study gives us an important understanding of how myelin repair can be promoted, which could open up new areas for treatment development."
Dr. Sorrel Bickley, Head of Biomedical Research at the UK MS Society
Learn how modified red blood cells could lead to new treatments for MS.
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MS: Treatments to reverse myelin damage step closer with brain repair study - Medical News Today
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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Cutting-edge stem cell therapy proves safe, but will it ever be effective? - Science Magazine
This morning, Australian biotech company Mesoblast Ltd (NASDAQ:MESO) announced encouraging phase 2 trial data regarding its regenerative therapy for chronic lower back pain (CLBP). Mesoblasts proprietary allogeneic Mesenchymal Precursor Cells (MPCs) are given to patients via a single injection and, in the clinical trial, have proved to spark significant improvement in both lower back pain and function that lasted for at least 36 months.
The sustained benefits on pain and function over three years seen with a single injection of Mesoblasts cell therapy have the potential to transform the treatment paradigm for chronic low back pain due to disc degeneration, said Dr. Hyun Bae, the trial investigator and Director of the Spine Institute.
According to Bae, there is growing evidence that disc degeneration can be healed instead of needing to be replaced or fused. Researchers are quickly arriving at this inflection point in the treatment of lower back pain, which is especially critical given the ongoing opioid abuse epidemic sweeping the nation.
Researchers believe that MPCs are turned on by signals in damaged tissues that spark factors to block damaging inflammation and begin repairing the afflicted area.
The phase 2 trial in question involved 100 patients, who were treated with either six million or 18 million MPCs via one intra-discal injection or a placebo of either saline or hyaluronic aid. The primary endpoints were a 50 percent drop in Visual Analog Scale (CAS), which is a pain metric, and a 15-point reduction in Oswestry disability index (ODI) at both the one and two year marks.
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The primary endpoint composite at the two-year mark was met by 41 percent of patients in the 6 million MPC arm, 35 percent in the 18 million arm, with just 18 percent and 13 percent in the placebo groups. The phase 2 results support the companys criteria for its ongoing phase 3 program.
Mesoblast is confident that the durable treatment outcomes in lower back pain are part of an overarching mechanism that might also have a positive effect in other types of chronic conditions where a single injection of MPCs can lead to sustained benefits. Two of these potential indications, according to Mesoblast, are chronic heart failure and biological-resistant rheumatoid arthritis.
Following the trial data being released, Maxim Groups Jason Kolbert reaffirmed a Buy rating on Mesoblasts stock and maintained a price target at $14.00. The upside indicated is 81 percent.
The market opportunity is significant and the treatment fits ideally within the existing paradigm the analyst told investors this morning. Injecting cells versus steroids with a better AE profile and now a better long-term result.
Earlier this month, Mesoblast announced that its MSC-100-IV therapy had been given Fast Track designation by the Food and Drug Administration (FDA) for its use in children with steroid refractory acute Graft Versus Host Disease (aGVHD). This type of designation shortens the FDA review path from ten months to six months, and certain portions of the Biologics License Application (BLA) can be sent in on a rolling basis rather than when everything is finished.
The author of this article holds no position in any of the stocks mentioned above.
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Mesoblast's (MESO) Regenerative Cell Therapy Proves Itself in Back Pain Trial - Economic Calendar
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 Florida'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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3 Women Blinded By Unproven Stem Cell Treatments - NPR
RenovaCare Inc. (OTCQB:RCAR) is a New York City-based biotechnology company developing its patented CellMist and SkinGun stem cell technologies for treating burns in weeks or less as well as treating chronic and acute wounds, acne scarring, and skin defects and diseases. In December, it received a U.S. patent for its SkinGun device.
Before joining RenovaCare, CEO Thomas Bold was CEO of StemCell Systems. He has more than 15 years of experience in medical biotechnology device manufacturing and stem cell platform development.
Harlan Levy: How does your CellMist technology specifically work?
Thomas Bold: Doctors isolate a high concentration of the most desirable stem cell population from a very small donor sample of the patient's own skin and suspended in the liquid CellMist Solution. It's then gently sprayed onto wound sites using our SkinGun, which looks like Captain Kirk's particle-beam gun, the "Phaser" in the Star Trek TV series.
The isolated cells include cells that proliferate rapidly in order to achieve quick re-epithelialization. This is the stage at which a burn is technically considered "healed" and patients are often discharged. The average person would recognize this healing phase as the point at which the wound develops a thin, shiny, pink-colored protective layer.
H.L.: What are existing burn treatments, and how do they compare with the SkinGun treatment?
T.B.: Traditional skin grafting has been the treatment for burns and wounds for centuries. More recently, mesh grafting has become the latest standard of care. This process surgically removes large sheets of healthy skin from the patient. Following this painful donor procedure, the sheet is punctured in a grid-like pattern to form an expandable mesh. Surgeons pull this mesh as wide as feasible and surgically stitch this skin to the patient's wound. The procedure is extremely painful, creates an additional wound at each donor site and results in poor cosmetic outcomes, often with scarred and deformed skin.
This transplanted skin can result in restricted joint movement and is unable to grow with the patient. Consequently, mesh graft patients require months and sometimes up to a year of physical therapy and can face psychological problems from the permanent disfigurement of scarring. In addition, long-term pain management with painkillers is very often necessary.
With the RenovaCare treatment technology, by spraying the patient's stem cells, the SkinGun overcomes the need for removing large sheets of donor skin, and the resultant healing does not require prolonged physical therapy. The spray procedure is gentle, and the skin that regrows looks, feels, and functions as the original skin that it replaces. Most often the healing process takes only a week.
It's very important to note here that a sheet of meshed skin covers only up to six times its original donor area. The RenovaCare system covers up to 100 times its donor skin sample. This is why the donor skin sample can be so small compared to the injured treatment area.
H.L.: What about scars and infection potential compared with conventional treatments?
T.B.: A wound heals from the edges towards the middle. The bigger the wound, the longer this process takes. And the longer this process takes, the higher the risk of infection and scarring.
Imagine a large burn of 20, 30, 40 percent of your total body surface. With our CellMist System, the doctor sprays the patient's own stem cells with a highly regenerative capacity onto the wound and, by doing so, creates tens of thousands of little regenerative islands across the wound. These islands grow outwards, ultimately connecting to each other to create a protective epithelial skin layer that covers the wound.
Experts believe the formation of this pink-colored layer marks the moment of re-epithelization where the risk of infection is reduced and the patient's wound is effectively healed. Beyond this stage, the cosmetic healing process also happens entirely natural to produce a scar-free result where, finally, skin color, tone and pigmentation are restored.
Since the RenovaCare spray procedure uses the patient's own stem cells, there isn't the risk of tissue rejection, infection, or ongoing immuno suppression therapy.
H.L.: What results have you found for patients using the SkinGun?
T.B.: We have many examples of patients recovering from severe burns within a week or two, scar-free, and walking away with unlimited joint restrictions.
In the case of one patient with severe electrical burns to over a third of his body, we were able to spray his wounds with 23 million stem cells isolated from a tiny two-inch-by two-inch sample of his own skin. Within five days of treatment, his chest and arms were already healed. Four days later, the patient was discharged from the hospital.
It's also important to note that reconstructive surgery for burn patients is especially challenging when tackling joints in the body. To this end, the authors of a case study in the reputable journal "Burns," said, "Cell-spray grafting is also especially suitable for hands and joint areas, where prolonged times to re-epithelization may significantly impact functionality and esthetic outcome."
H.L.: What different uses does the SkinGun have beside burns?
T.B.: Currently, we are focusing on severe second-degree burns, but we see the RenovaCare technology also applicable for other indications such as cosmetic procedures targeting skin pigmentation disorders, scar treatment, and other related conditions.
Our goal is to bring to market the world's most advanced technology for skin repair using a patient's own stem cells.
H.L.: Is there a record of the SkinGun use in the States and abroad?
T.B.: Having treated 72 burn patients to date, the company's early clinical target is burns with follow-on indications, including chronic wounds and cosmetic procedures.
H.L.: How much research went into creating the SkinGun and over what time period?
T.B.: The birth of RenovaCare technology goes back to the early 2000s in Berlin, Germany. Researchers, at that time, were trying to "grow" skin by seeding stem cells inside multi-dimensional bioreactors. They soon discovered that these artificial chambers were no match for the growth of the same cells when transplanted inside a human body; thus, the birth of a concept to use a patient's own wound as a natural bioreactor.
A study published in "Advances in Plastic Surgery" highlights 19 early patients with deep dermal wound burns to the face and neck, complex three-dimensional surfaces. Researchers achieved such outstanding results using our cell spray that they refused to perform further skin grafting. Instead, surgeons adopted our founding technology as their standard of care.
Let me quote from the surgeons' study, which states
"We refuse to perform a prospective randomized study with groups in which traditional skin grafting and/or wound healing are still applied for the therapy for deep dermal burns due to the excellent results in our study. The method of CEA spray application has become our standard of care for these indications. The faster wound closure, the promotion of spontaneous wound healing by keratinocyte application, as well as the preservation of donor sites are further advantages of the method."
The same paper concluded that "using a spray technique results in excellent cosmetic outcomes compared with any other method."
H.L.: How has the technology changed since then?
T.B.: Since the time of this early approach, our technology has evolved and matured significantly. Our cell isolation no longer requires complex procedures, culturing, expansion, and processing time, and our stem cell spray device no longer requires multiple hand-assembled parts. Its independent power and flow-control unit has been condensed in size from a 2-foot cube down to a 9-volt battery placed inside the handle of a single handheld spray gun.
H.L.: What is the potential market for the technology in dollars and number of patients?
T.B.: Conservatively speaking, the market for our technology exceeds $50 billion. There are nearly a million people who suffer from burns each year in the U.S. alone. According to the American Burn Association, burn injuries continue to be one of the leading causes of accidental death and injury in the U.S, and one civilian fire death occurs every two hours and forty minutes.
H.L.: How much would you estimate the treatment cost may be for each different use?
T.B.: The SkinGun technology is currently under development and not approved for clinical use in the U.S., so it's too early to talk about what the treatment will cost. We have always been mindful of reimbursement, and nearly two years ago, we commissioned an investigation into the reimbursement pathway for our CellMist System. We know that reimbursement opportunities are available by way of current coding and practices.
We have further investigated and evaluated the "bundling" approach currently advocated for by insurers and are confident that that our technology is well placed to take advantages of any shift towards such a model.
H.L: What is the schedule to get Federal Drug Administration clearance?
T.B.: In order to achieve FDA clearance for the CellMist System and the SkinGun, we will be working to show our technology is safe and prove its efficacy within applicable clinical trial formats and according to the relevant regulatory requirements. I can't speculate as to how long the FDA clearance process will take, and, therefore, it's hard to speculate when our product will be commercialized.
H.L.: What other products are you investigating and how may they work?
T.B.: We are focusing on bringing the SkinGun and our stem cell spray technology to market at this time.
H.L.: What is your background, including age, education, prior employment?
T.B.: Before joining RenovaCare I worked as the CEO of StemCell Systems GmbH, a Berlin-based biomedical company engaged in the development and commercialization of advanced cell culture bioreactors. I have more than 15 years of professional business experience in the field of medical biotechnology device manufacturing, stem cell culture technology platform development and regenerative medicine research project management and product development. I also co-founded several start-up companies in Germany.
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Read more:
RenovaCare: Stem Cell Treatment Heals Burns In Weeks Not Months - Seeking Alpha
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Patients Lose Sight After Stem Cells Are Injected Into Their Eyes - New York Times
"The impact of Alzheimer's disease is vast, far exceeding the medical community's current ability to treat it," said Joshua M. Hare, M.D., Longeveron's Co-Founder and Chief Science Officer. "Regenerative medicine and cell-based therapies offer a promising new approach to close this gap and address the urgent need for effective therapies to combat the condition."
An important component in the progression of Alzheimer's disease is neuroinflammation. Longeveron was recently awarded a $1 million Part the Cloud Challenge on Neuroinflammation grant from the Alzheimer's Association to help support this research.
"Adult stem cells are very potent anti-inflammatories. The characteristic amyloid plaques found in the brains of Alzheimer's disease patients produce inflammation, and stem cells can reduce inflammation," explained Bernard S. Baumel, M.D., Principal Investigator for the trial. "Alzheimer's also impairs the brain's ability to adequately produce new brain cells in the memory area known as the hippocampus. Stem cells can stimulate the brain to produce these new cells needed to form memory. We believe that an infusion of LMSCs may improve the condition or at least halt the progression of the disease."
Prior research shows that adult MSCs target and reduce inflammation, promote tissue repair and improve brain function in mouse models of Alzheimer's disease. Longeveron's trial is the first U.S. clinical study of exogenously administered mesenchymal stem cells derived from the bone marrow of healthy adult donors for treating Alzheimer's disease.
To learn about participating in the clinical trial, visit: https://clinicaltrials.gov/ct2/show/NCT02600130
About Longeveron
Longeveron is a regenerative medicine therapy company founded in 2014. Longeveron's goal is to provide the first of its kind biological solution for aging-related diseases, and is dedicated to developing safe cell-based therapeutics to revolutionize the aging process and improve quality of life. The company's research focus areas include Alzheimer's disease, Aging Frailty and the Metabolic Syndrome. Longeveron produces LMSCs in its own state-of-the-art cGMP cell processing facility. http://www.longeveron.com
Contact: Suzanne Liv Page spage@longeveron.com 305.342.9590
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/longeveron-achieves-milestone-in-groundbreaking-stem-cell-trial-for-alzheimers-disease-300424206.html
SOURCE Longeveron
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Longeveron Achieves Milestone in Groundbreaking Stem Cell Trial for Alzheimer's Disease - PR Newswire (press release)