Report on remission in patients with MS three years after stem cell transplant

Three years after a small number of patients with multiple sclerosis (MS) were treated with high-dose immunosuppressive therapy (HDIT) and then transplanted with their own hematopoietic stem cells, most of the patients sustained remission of active relapsing-remitting MS (RRMS) and had improvements in neurological function, according to a study published online by JAMA Neurology.

MS is a degenerative disease and most patients with RRMS who received disease-modifying therapies experience breakthrough disease. Autologous (using a patient's own cells) hematopoietic cell transplant (HCT) has been studied in MS with the goal of removing disease-causing immune cells and resetting the immune system, according to the study background.

The Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) study examines the effectiveness of early intervention with HDIT/HCT for patients with RRMS and breakthrough disease. The article by Richard A. Nash, M.D., of the Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center, Denver, and coauthors reports on the safety, efficacy and sustainability of MS disease stabilization though three years after the procedures. Patients were evaluated through five years.

Study results indicate that of the 24 patients who received HDIT/HCT, the overall rate of event-free survival was 78.4 percent at three years, which was defined as survival without death or disease from a loss of neurologic function, clinical relapse or new lesions observed on imaging. Progression-free survival and clinical relapse-free survival were 90.9 percent and 86.3 percent, respectively, at three years. The authors note that adverse events were consistent with the expected toxic effect of HDIT/HCT and that no acute treatment-related neurologic adverse events were seen. Improvements in neurologic disability, quality-of-life and functional scores also were noted.

"In the present study, HDIT/HCT induced remission of MS disease activity up to three years in most participants. It may therefore represent a potential therapeutic option for patients with MS in whom conventional immunotherapy fails, as well as for other severe immune-mediated diseases of the central nervous system. Most early toxic effects were hematologic and gastrointestinal and were expected and reversible. Longer follow-up is needed to determine the durability of the response," the authors conclude.

Editorial: Moving Targets for Stem Cell Transplantation for Patients with MS

In a related editorial, M. Mateo Paz Soldn, M.D., Ph.D., of the University of Utah, Salt Lake City, and Brian G. Weinshenker, M.D., of the Mayo Clinic, Rochester, Minn., write: "This study and another phase 2 single-arm study leave little doubt that high-dose immunotherapy is able to substantially suppress inflammatory disease activity in patients with MS who have active disease in the short term. There is some evidence for long-term suppression of MS. Lessons have been learned about how treatment-related morbidity and mortality may be reduced. However, deaths have occurred, even in small studies, and aggressive regimens have resulted in lymphomas associated with Epstein-Barr virus."

"Nash et al show evidence of prolonged depletion of memory CD4+ cells, depletion of CD4+-dominant T-cell receptor clones and evidence of 'immune reset'; however, clinical or radiologic evidence of relapse trumps immunologic evidence of immune reset, and this study raises concern that those end points have not been adequately achieved. The jury is still out regarding the appropriateness and indication of HCT for MS," the authors conclude.

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Report on remission in patients with MS three years after stem cell transplant

Center for Stem Cell Biology | Memorial Sloan Kettering …

The Center for Stem Cell Biology (CSCB) was established in 2010 to serve as a hub for existing stem cell efforts at Memorial Sloan Kettering Cancer Center. The center also supports targeted recruitment of stem cell faculty and provides resources for stem cell research such as core facilities and trainings programs.

Memorial Sloan Kettering has been a leader in various aspects of stem cell research for many years. It has been at the forefront of realizing the potential of hematopoietic stem cells in the treatment of hematopoietic malignancies, the use of umbilical cord blood as a source of stem cells suitable for transplantation, and the isolation of human mesenchymal stem cells. In recent years research has expanded to new areas such as neural stem cells, embryonic stem cells, and induced pluripotent stem cells. The CSCB will link these existing stem cell research efforts and build the resources critical for new developments in the future.

Career Opportunities Faculty positions are currently available in the Stem Cell Biology Program More

To achieve these goals the CSCB will bring together scientists across various programs with a broad range of expertise in the following areas: cancer pathogenesis, cell biology, chemical biology, computational biology, developmental biology, and pharmacology. These partnerships will facilitate research projects that transcend traditional departmental boundaries to explore the full potential of stem cells, ranging from basic developmental studies to the use of human stem cells in drug discovery. Another core mission of the CSCB is the training of investigators in stem cell technologies such as induced pluripotency, directed differentiation, genetic modification, and prospective purification of stem cells. Finally, the CSCB links stem cell efforts at Memorial Sloan Kettering with the Tri-Institutional Stem Cell Initiative, a collaborative program of Memorial Sloan Kettering, The Rockefeller University, and Weill Cornell Medical College, as well as with other national and international stem cell organizations.

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Stem Cell Transplantation Centre Opens in Varna

A new stem cell transplantation centre opened on Monday in the St. Marina hospital in Varna, reports the bTV national channel.

It is the most up-to-date in Bulgaria and is expected to partially solve the shortage of such treatment of patients with oncological diseases.

According to the head of the heaematology clinic of the St. Marina hospital, Riana Gercheva, the stem cell treatment often is a life-saving procedure for cancer patients whose bone marrow has been severely damaged by chemotherapy.

According to the deputy rector of the Varna Medical University, Deyan Grancharov, there are two similar centres in Sofia and Plovdiv, but the demand was much higher. Now it will be much cheaper and easily accessible than similar treatment in Israel, for example, Grancharov said.

The capacity of the Varna centre is up to 100 patients per year. The procedure is free of charge for the insured.

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Stem Cell Transplantation Centre Opens in Varna

365 days: 2014 in science

Keith Vanderlinde/NSF

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

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

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

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

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

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

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

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

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

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365 days: 2014 in science

Stem cells faulty in Duchenne muscular dystrophy, Stanford researchers find

PUBLIC RELEASE DATE:

17-Dec-2014

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

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

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

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

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

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

A devastating disease

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

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Stem cells faulty in Duchenne muscular dystrophy, Stanford researchers find

The Stem Cell Theory of Cancer – Overview – Ludwig Center …

Research has shown that cancer cells are not all the same. Within a malignant tumor or among the circulating cancerous cells of a leukemia, there can be a variety of types of cells. The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. In this view, cancer cells that are not stem cells can cause problems, but they cannot sustain an attack on our bodies over the long term.

The idea that cancer is primarily driven by a smaller population of stem cells has important implications. For instance, many new anti-cancer therapies are evaluated based on their ability to shrink tumors, but if the therapies are not killing the cancer stem cells, the tumor will soon grow back (often with a vexing resistance to the previously used therapy). An analogy would be a weeding technique that is evaluated based on how low it can chop the weed stalksbut no matter how low the weeks are cut, if the roots arent taken out, the weeds will just grow back.

Another important implication is that it is the cancer stem cells that give rise to metastases (when cancer travels from one part of the body to another) and can also act as a reservoir of cancer cells that may cause a relapse after surgery, radiation or chemotherapy has eliminated all observable signs of a cancer.

One component of the cancer stem cell theory concerns how cancers arise. In order for a cell to become cancerous, it must undergo a significant number of essential changes in the DNA sequences that regulate the cell. Conventional cancer theory is that any cell in the body can undergo these changes and become a cancerous outlaw. But researchers at the Ludwig Center observe that our normal stem cells are the only cells that reproduce themselves and are therefore around long enough to accumulate all the necessary changes to produce cancer. The theory, therefore, is that cancer stem cells arise out of normal stem cells or the precursor cells that normal stem cells produce.

Thus, another important implication of the cancer stem cell theory is that cancer stem cells are closely related to normal stem cells and will share many of the behaviors and features of those normal stem cells. The other cancer cells produced by cancer stem cells should follow many of the rules observed by daughter cells in normal tissues. Some researchers say that cancerous cells are like a caricature of normal cells: they display many of the same features as normal tissues, but in a distorted way. If this is true, then we can use what we know about normal stem cells to identify and attack cancer stem cells and the malignant cells they produce. One recent success illustrating this approach is research on anti-CD47 therapy.

Next Section >> Case Study: Leukemia

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The Stem Cell Theory of Cancer - Overview - Ludwig Center ...

Stem cells: The black box of reprogramming

Nik Spencer/Nature

Eggs and sperm do it when they combine to make an embryo. John Gurdon did it in the 1960s, when he used intestinal cells from tadpoles to generate genetically identical frogs. Ian Wilmut did it too, when he used an adult mammalian cell to make Dolly the sheep in 1996. Reprogramming reverting differentiated cells back to an embryonic state, with the extraordinary ability to create all the cells in the body has been going on for a very long time.

Scientific interest in reprogramming rocketed after 2006, when scientists showed that adult mouse cells could be reprogrammed by the introduction of just four genes, creating what they called induced pluripotent stem (iPS) cells1. The method was simple enough for almost any lab to attempt, and now it accounts for more than a thousand papers per year. The hope is that pluripotent cells could be used to repair damaged or diseased tissue something that moved closer to reality this year, when retinal cells derived from iPS cells were transplanted into a woman with eye disease, marking the first time that reprogrammed cells were transplanted into humans (see Nature http://doi.org/xhz; 2004).

There is just one hitch. No one, not even the dozen or so groups of scientists who intensively study reprogramming, knows how it happens. They understand that differentiated cells go in, and pluripotent cells come out the other end, but what happens in between is one of biology's impenetrable black boxes. We're throwing everything we've got at it, says molecular biologist Knut Woltjen of the Center for iPS Cell Research and Application at Kyoto University in Japan. It's still a really confusing process. It's very complicated, what we're doing.

Kerri Smith talks to researcher Andras Nagy and reporter David Cyranoski about reprogramming cells.

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One of the problems, stem-cell biologists say, is that their starting population contains a mix of cells, each in a slightly different molecular state. And the process for making iPS cells is currently inefficient and variable: only a tiny fraction end up fully reprogrammed and even these may differ from one another in subtle but important ways. What is more, the path to reprogramming may vary depending on the conditions under which cells are being grown, and from one lab to the next. This makes it difficult to compare experimental results, and it raises safety concerns should a mix of poorly characterized cells be used in the clinic.

But new techniques are starting to clarify the picture. By carrying out meticulous analyses of single cells and amassing reams of detailed molecular data, biologists are identifying a number of essential events that take place en route to a reprogrammed state. This week, the biggest such project an international collaboration audaciously called Project Grandiose unveiled its results26. The scientists involved used a battery of tests to take fine-scale snapshots of every stage of reprogramming and in the process, revealed an alternative state of pluripotency. It was the first high-resolution analysis of change in cell state over time, says Andras Nagy, a stem-cell biologist at Mount Sinai Hospital in Toronto, Canada, who led the project. I'm not shy about saying grandiose.

I'm not shy about saying grandiose.

But there is more to do if scientists want to control the process well enough to generate therapeutic cells with ease. Yes, we can make iPS cells and yes we can differentiate them, but I think we feel that we do not control them enough says Jacob Hanna, a stem-cell biologist at the Weizmann Institute of Science in Rehovot, Israel. Controlling cell behaviour at will is very cool. And the way to do it is to understand their molecular biology with great detail.

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Nivolumab Shows Significant Benefit for Hodgkin's Lymphoma in Mayo Clinic Co-Led Phase I Study

Released: 5-Dec-2014 11:00 AM EST Embargo expired: 6-Dec-2014 1:00 PM EST Source Newsroom: Mayo Clinic Contact Information

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Nivolumab shows significant benefit for Hodgkin’s lymphoma in Mayo Clinic co-led phase I study

Newswise A phase I clinical trial of nivolumab found that the immune-boosting drug is a highly effective therapy for Hodgkins lymphoma. The multi-institution study, led by Mayo Clinic, indicated that the drug was safe and led to an 87 percent response rate in patients who had failed on other treatments. Results of the study appear in the New England Journal of Medicine.

The findings support further development of nivolumab, which enhances the immune systems ability to detect and kill cancer cells. The drug has already demonstrated benefit in the treatment of other cancers, particularly melanoma, renal cell cancer, lung cancer and bladder cancer.

Nivolumab is a very promising agent that is reasonably well-tolerated and can easily be combined with other agents in the future, says Stephen Ansell, M.D., Ph.D., a hematologist and co-lead author of the study. There is evidence now that you can fight cancer by optimizing your immune function, either by enhancing signals that stimulate the immune response or blocking signals that dampen it.

The immune systems T cells are specifically trained to fight infectious diseases and cancer. When these cells are called to active duty, their extracellular armor is marked with an immune checkpoint protein, a type of off switch called PD1 that can be used to shut down the immune response. Other immune cells carry molecular keys or ligands named PD-L1 or PD-L2, which can flip that switch to protect normal tissues from collateral damage.

Cancer cells can co-opt this PD-1 pathway by making their own copy of the keys and using them to turn off T cells before they attack. The malignant cell in Hodgkins lymphoma, the Reed-Sternberg cell, has very high levels of PD-L1 and PD-L2 on its cell surface. Therefore, Dr. Ansell and his colleagues hypothesized that using the known immune checkpoint inhibitor nivolumab to block PD1 could prevent these malignant cells from evading immune detection.

In the phase I study, the researchers gave nivolumab every two weeks to 23 patients with relapsed or refractory Hodgkin's lymphoma who were heavily pretreated. The drug appeared to be safe at its highest doses of 3 mg/kg, with rash and decreased platelet counts being the most common drug-related adverse events.

The researchers observed substantial therapeutic activity, with an objective response rate of 87 percent. Seventeen percent of patients had complete responses and 70 percent had partial responses. Progression-free survival at 24 weeks was 86 percent; 11 patients are still in the study. Six patients discontinued participation because of stem-cell transplantation, four because of disease progression, and two because of drug toxicity.

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Nivolumab Shows Significant Benefit for Hodgkin's Lymphoma in Mayo Clinic Co-Led Phase I Study

Newport Beach Stem Cell Treatment Center – Stem Cell …

The Newport Beach Stem Cell Treatment Center provides cutting-edge care for patients with a wide variety of degenerative disorders using adult stem cell regenerative therapy. Our highly trained physicians and medical team are focused on providing you with the most innovative techniques and advanced procedures for harvesting and deploying adult stem cells from your own fat. We are also committed to clinical research and the advancement of regenerative medicine.

We are dedicated to the principles of personalized patient care and individualized attention. Our plastic surgeon, a pioneer in liposuction, and topnotch team of registered nurses and technicians are experienced in harvesting and deploying adult stem stems. In addition, our comfortable in-office surgery center is fully accredited by the Institute for Medical Quality, a division of the California Medical Association. Our goal is to provide you with the best possible care in a friendly and professional atmosphere.

Fat is the bodys most abundant repository of adult stem cells, containing thousands of times more stem cells than bone marrow. New technologies at the Newport Beach Stem Cell Treatment Center make it possible for us to remove a few ounces of a patients fat through liposuction, separate out the stem cells in a special process that yields extremely high numbers of viable cells, and return them back into the patients body via IV or injection. Performed in a physicians office under sedation and local anesthesia and using a sterile closed system technology (so the cells never come into contact with the environment), there is minimal discomfort and risk of infection. And because the cells come from the patients own body, there is no risk of rejection or disease transmission.

Posted by Mark Baldwin on Nov 28, 2012 in Cardiac / Pulmonary

Posted by Mark Baldwin on Nov 28, 2012 in Cardiac / Pulmonary

Posted by Mark Baldwin on Nov 28, 2012 in Cardiac / Pulmonary

Posted by Mark Baldwin on Nov 28, 2012 in Cardiac / Pulmonary

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Donor: The German teenager who saved my life

Sue Walters only chance of survival from leukaemiawas a stem cell transplant No one in her family matched her tissue type Doctors searched the worldwide donor register They found Nicola Gerber, a student from Mechern, near the French border

By Chloe Lambert for the Daily Mail

Published: 20:21 EST, 17 November 2014 | Updated: 04:28 EST, 18 November 2014

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When Sue Walters was diagnosed with leukaemia, she hoped that the best of medical science would be used to cure it.

What she could never have anticipated was that her life would be saved by an 18-year-old boy from a remote German village.

Sues only chance of survival was a stem cell transplant previously known as a bone marrow transplant.

What Nicola has done is amazing it really is a gift of life. If I hadnt had the transplant, it was unlikely Id have lived beyond three months,' said Sue Walters of her donor Nicola Gerber

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Donor: The German teenager who saved my life