NIBSC/Science Photo Library

HIV attacks a type of immune cell known as a T cell (shown here) using a protein encoded by the CCR5 gene.

A clinical trial has shown that a gene-editing technique can be safe and effective in humans. For the first time, researchers used enzymes called zinc-finger nucleases (ZFNs) to target and destroy a gene in the immune cells of 12 people with HIV, increasing their resistance to the virus to the virus. The findings are published today in The New England Journal of Medicine1.

This is the first major advance in HIV gene therapy since it was demonstrated that the Berlin patient Timothy Brown was free of HIV, says John Rossi, a molecular biologist at the Beckman Research Institute of the City of Hope National Medical Center in Duarte, California. In 2008, researchers reported that Brown gained the ability to control his HIV infection after they treated him with donor bone-marrow stem cells that carried a mutation in a gene called CCR5. Most HIV strains use a protein encoded by CCR5 as a gateway into the T cells of a hosts immune system. People who carry a mutated version of the gene, including Brown's donor, are resistant to HIV.

But similar treatment is not feasible for most people with HIV: it is invasive, and the body is likely to attack the donor cells. So a team led by Carl June and Pablo Tebas, immunologists at the University of Pennsylvania in Philadelphia, sought to create the beneficial CCR5 mutation in a persons own cells, using targeted gene editing.

The researchers drew blood from 12 people with HIV who had been taking antiretroviral drugs to keep the virus in check. After culturing blood cells from each participant, the team used a commercially available ZFN to target the CCR5 gene in those cells. The treatment succeeded in disrupting the gene in about 25% of each participants cultured cells; the researchers then transfused all of the cultured cells into the participants. After treatment, all had elevated levels of T cells in their blood, suggesting that the virus was less capable of destroying them.

Six of the 12 participants then stopped their antiretroviral drug therapy, while the team monitored their levels of virus and T cells. Their HIV levels rebounded more slowly than normal, and their T-cell levels remained high for weeks. In short, the presence of HIV seemed to drive the modified immune cells, which lacked a functional CCR5 gene, to proliferate in the body. Researchers suspect that the virus was unable to infect and destroy the altered cells.

They used HIV to help in its own demise, says Paula Cannon, who studies gene therapy at the University of Southern California in Los Angeles. They throw the cells back at it and say, Ha, now what?

In this first small trial, the gene-editing approach seemed to be safe: Tebas says that the worst side effect was that the chemical used in the process made the patients bodies smell bad for several days.

The trial isnt the end game, but its an important advance in the direction of this kind of research, says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Its more practical and applicable than doing a stem-cell transplant, he says, although it remains to be seen whether it is as effective.

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Gene-editing method tackles HIV in first clinical test

Inhibition of a prostaglandin with nonsteroidal anti-inflammatory drugs has been found to cause stem cells to leave marrow, where they could be harvested for patients with blood disorders

Tino Soriano/National Geographic Society/Corbis

Aspirin-like drugs could improve the success of stem-cell transplants for patients with blood or bone-marrow disorders, a study suggests. The compounds coax stem cells from bone marrow into the bloodstream where they can be harvested for use in transplantation and they do so with fewer side effects than drugs now in use.

For patients with blood disorders such as leukemia, multiple myeloma or non-Hodgkins lymphoma, transplantation of haematopoietic stem cells precursor cells that reside in the bone marrow and give rise to all types of blood cell can be an effective treatment.

Previous work has shown that prostaglandin E2, or PGE2, a lipid known to regulate multiple bodily reactions including pain, fever and inflammation, also has a role in keeping stem cells in the bone marrow. In the latest study, researchers show that in mice, humans and baboons, inhibition of PGE2 with non-steroidal anti-inflammatory drugs (NSAIDs) causes stem cells to leave the bone marrow.

Releasing the stem cells The team gave baboons and humans an NSAID called meloxicam. They saw a subsequent increase in the numbers of haematopoietic stem cells in the bloodstream.

The researchers think that the departure of stem cells is caused by the disturbance of a group of bone-forming cells called osteoblasts. These cells secrete a protein called osteopontin that hooks the stem cells to the bone marrow. Inhibiting PGE2 would disrupt the production of osteopontin.

At present, doctors use a drug called filgrastim to mobilize haematopoietic stem cells in donors or in patients undergoing autotransplantation (in which they receive their own stem cells). In patients with multiple myeloma or non-Hodgkins lymphoma, however, and in some donors, stem cells dont mobilize well with filgrastim and other drugs in its class. Using NSAIDs such as meloxicam could enhance filgrastims efficacy, says lead author Louis Pelus of the Indiana University School of Medicine in Indianapolis. The study appears in Nature.

Meloxicam also has comparatively few side effects, says Pelus. He and his colleagues found that other NSAIDs, including aspirin and ibuprofen, can also mobilize haematopoietic stem cells, but these drugs can cause gastrointestinal upset in patients. PGE2 controls the secretion of hydrochloric acid in the stomach, and when you block that youve reduced your ability to control acid secretion. Meloxicam doesnt do that as badly as many of the other [drugs] do, he says.

For Charles Craddock, director of the blood and marrow transplant unit at the Queen Elizabeth Hospital in Birmingham, UK, the results might also hold clues about how to mediate the tricky process of getting cells back to the bone marrow once transplanted. If youre beginning to understand what mediates cells moving out, you might be able to understand what mediates cells moving in. If you can make bone marrow more sticky, when you put cells back, you might be able to keep them in.

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Painkillers Could Prove Helpful in Stem-Cell Transplants

Engineering a patients own immune cells to resist HIV could eliminate the need for lifelong antiretroviral therapies.

The immune cells of HIV patients can be genetically engineered to resist infection, say researchers. In a small study in humans, scientists report that by creating a beneficial mutation in T cells, they may be able to nearly cure patients of HIV.

In a study published in the New England Journal of Medicine on Wednesday, researchers report that they can use genome editing to re-create the rare mutations responsible for protecting about 1 percent of the population from the virus in infected patients. They report that some of the patients receiving the genome-modifying treatment showed decreased viral loads during a temporary halt of their antiretroviral drugs. In one patient, the virus could no longer be detected in his blood.

Zinc-finger nucleases are one of a few genome-editing tools that researchers use to create specific changes to the genomes of living organisms and cells (see Genome Surgery). Scientists have previously used genome-editing techniques to modify DNA in human cells and nonhuman animals, including monkeys (see Monkeys Modified with Genome Editing). Now, the NEJM study suggests the method can also be safely used in humans.

From each participating patient, the team harvested bone marrow stem cells, which give rise to T cells in the body. They then used a zinc finger nuclease to break copies of the CCR5 gene that encodes for proteins on the surface of immune cells that are a critical entry point of HIV. The stem cells were then infused back into each patients bloodstream. The modification process isnt perfect, so only some of the cells end up carrying the modification. About 25 percent of the cells have at least one of the CCR5 genes interrupted, says Edward Lanphier, CEO of Sangamo Biosciences, the Richmond, California, biotech company that manufactures zinc finger nucleases.

Because the cells are a patients own, there is no risk of tissue rejection. The modified stem cells then give rise to modified T cells that are more resistant to infection by HIV, say the researchers.

One week after the infusion, researchers were able to find modified T cells in the patients blood. Four weeks after the infusion, six of the 12 patients in the study temporarily stopped taking their antiretroviral drugs so the researchers could assess the effect of the genome-editing treatment on the amount of the virus in the patients bodies. In four of these patients, the amount of HIV in the blood dropped. In one patient, the virus could no longer be detected at all. The team later discovered that this best responder had naturally already had one mutated copy of the CCR5 gene.

Patients who carry one broken copy of the CCR5 progress to AIDS more slowly than those who dont, says Bruce Levine, a cell and gene therapy researcher at the University of Pennsylvania School of Medicine and coauthor on the study. Because all of the cells in that best-responder patient already carried one disrupted copy of CCR5, the modification by the zinc finger nuclease led to T cells with no functional copies of the gene. That means the cells are fully resistant to HIV infection. The team is now working to increase the number of immune cells that end up carrying two broken copies of CCR5.

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Can Gene Therapy Cure HIV?

Watch the video above:Mississauga woman looking for bone marrow donor against allodds. Laura Zilke reports.

TORONTO A woman in dire need of a bone marrow transplant is trying to find a match within her underrepresented community.

Dorothy Vernon-Brown is African-Canadian and was recently diagnosed with Acute Myeloid Leukemia. Chemotherapy has helped and shes currently in remission but still needs a transplant.

You dont know if youll ever find a match, she said. Next to Caucasians, African-Canadians have the greatest need for stem cells.

Shes most likely to find a match within her own ethnic community but in Canada, only one per cent of all people registered to donate bone marrow are black.

We have patients from all ethnic communities that are currently in need of a stem cell transplant and they are relying on members of their community, whether they are living here in Canada or anywhere in the world, Mary-Lynn Pride, a spokesperson for OneMatch said.

OneMatch does have access to donor registries in over 70 countries but in Vernon-Browns native Jamaica, there isnt a registry.

Theres no studies as to why the level of African-Canadian donors is so low in Canada but she believes its cultural.

Many of us come here [and] its not part of our culture, she said. We continue with what we know.

Its not difficult to register. A simple cheek swab is all thats needed to get your name on the donor list.

See the article here:
Woman looking for bone marrow donor among underrepresented ethnic group

Jesse Freeman, 71, suffered a major heart attack at home Had surgery to repair a blocked artery and to insert a stent to keep it open He was then asked to take part in a new study into the use of stem cells These are 'master cells' which can turn into almost any other type of cell in the body, replacing damaged cells He had bone marrow removed from his hip and infused into his heart It is hoped this will regenerate to help heal his damaged heart

By Emma Innes

PUBLISHED: 08:36 EST, 3 March 2014 | UPDATED: 08:52 EST, 3 March 2014

A British man has become the second patient in a Europe to have pioneering stem cell treatment in a bid to prolong his life.

Jesse Freeman, 71, was invited to take part in the landmark trial after suffering a major heart attack at home.

Surgeons repaired a blocked artery and inserted a stent to keep it open after he was rushed to hospital.

Jesse Freeman (pictured with his wife, Christine) has become the second person in Europe to have pioneering stem cell treatment after a heart attack. It is hoped the procedure will cause his damaged heart muscle to regenerate and that it could eventually become common practice in the treatment of heart attack patients

But while recovering in hospital, he was asked to take part in the major new study to see if heart attack patients can benefit from being treated with their own stem cells.

These are 'master cells' which can turn into almost any other type of cell in the body, replacing damaged cells.

Doctors at the London Chest Hospital, in Bethnal Green, removed bone marrow from Mr Freeman, a grandfather, without general anaesthetic and the cells were then infused into his heart.

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Is this the heart attack treatment of the future? British grandfather has stem cells taken from his hip and injected ...

Jesse Freeman, 71, had stem cells from his bone marrow injected into his heart after he had a cardiac arrest. With his wife Christine, 67

Mike Brooke, Reporter Sunday, March 2, 2014 6:00 PM

A 71-year-old man has become one of the first heart attack victims to receive pioneering stem cell surgery to see if it will help his recovery.

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On March 12, I will be 72, so the stem cell surgery for me is an early birthday present just to be alive, admits Jesse Freeman.

I was never ill in my life, then one day I was indoors and didnt feel great. I thought it was an infection that started in my jaw, then spread to my chest. I had a shower and drove down to Harold Wood walk-in centre.

I had extremely high blood pressure and they told me I had had a heart attack.

They took me to The London Chest Hospital and I was being operated on within 10 minutes.

The hospital saved my life they removed the blockage and put in a wire mesh stent to keep the artery open.

The doctors asked me while I was in recovery if I would take part in the stem cell trial.

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An advanced surgery was performed at TOSH hospital on Saturday to treat a patient with knee arthritis, with the damaged cartilage in the knee regenerated using stem cells.

Prof. A.A. Shetty, director of minimally invasive surgery and stem cell research at Canterbury Christchurch University, UK, who performed the surgery, said all the Indian Council of Medical Researchs guidelines were adhered to while performing the procedure. He was speaking at a press meet on Saturday.

Under an earlier version of this technique, stem cells harvested in the bone marrow had to be cultured in the lab and then injected into the knee after six weeks. There were several disadvantages with this technique longer hospital stay, increased chances of infection, lower success rates and increased costs, he said.

However, under the new technique, the stem cells are harvested and centrifuged within the operation theatre. The stem cell concentrate is then mixed with a special fibrin gel and inserted directly at the site of the damaged cartilage through a keyhole procedure.

This surgery is less expensive, at around Rs. 75,000, and the patient can go home the next day. Its failure rate is only 10 to 15 per cent and it can also be performed on patients with advanced osteoarthritis, Prof. Shetty said.

A 49-year-old woman, on whom the surgery has been performed, is currently recovering at the hospital.

Prof. Seok Jung Kim, director of the regenerative medical system, South Korea, and S.H. Jaheer Hussain, orthopaedic and trauma surgeon, TOSH hospital, also participated in the meet.

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Chennai TOSH hospital treats knee arthritis with stem cells

Callie (left) and her sister Alaina between transplants

Tonight, local rapper Kusha Tarantino will host a jam-packed hip-hop bill at Fitzgeralds. When James Courtney first pitched me an article about the show, I wrote back fastest way to my heart!

Thats not because I particularly love Kusha, (though he seemed like a smart, passionate guy in the subsequent article James wrote) but because I fully support the concerts secondary mission: signing people up for the National Marrow Donor Program.

I myself have donated marrow once and stem cells once (these are two different methods to get the same type of cells into the patient in need). Both times it was a treatment of the last resort for the patient, my sister Alaina, who spent several years in her late teens battling a particularly aggressive form of leukemia. Sadly, my donations did not save her life, but they did prolong it. Without the marrow and stem cell transplant, Alaina wouldnt have been well enough to leave the hospital and recover at home. She wouldnt have lived long enough to graduate high school and apply to college. For many other patients (typically those with blood disorders or blood cancer), the transplant does save their life.

Signing up for the marrow donor registry, which you can do for free tonight at the Kusha Tarantino show thanks to the organization LOVE HOPE STRENGTH, is absurdly easy. They swab your cheek to get your DNA, and then send it off to NMDP where theyll scan in for human leukocyte antigens (HLA). When a patient in need of a bone marrow or stem cell transplant cant find one in their own family, doctors turn to the registry to find a donor.

This is the part that makes people nervous. What if they call me? people ask when I tell them about the registry. Well, a) you can always decline (odds are 1 in 540 that youll get called to be a donor sometime in your life if youre on the registry) and b) the donation is also pretty easy, especially consider the end result is generally life-saving, or at least life-prolonging. Im in a unique position to tell you about both, so here it goes:

Bone Marrow: This is an outpatient surgery. Dont worry, in both cases you have several weeks to prepare, its not like they call you and tell you to be in surgery prep the next day. A doctor in your city or nearby will help you through the process and work with you to schedule the surgery date. I was in and out in one day, and the surgery had general anesthesia, so I dont remember any of it. They extract the marrow with a needle from your hip/pelvis area. Afterward, I felt a little sore there, like I had fallen and bruised my tailbone. I had two teeny tiny scars that are no longer visible. The soreness lasted for a few days, and in about a week I was feeling normal. I was in college at the time and donated over spring break, so I didnt have to worry about taking off of work or school, but Id probably recommend taking the next day off, if only because it hurts to sit down in a chair for 8-10 hours. Standing desk or working from home? No problem.

Peripheral Blood Stem Cell: This is a non-surgical procedure. As in bone marrow donation, a doctor will work with you to prepare and schedule your appointment. Unlike bone marrow donation, for five days leading up to stem cell donation you have to take some injections that boost your stem cell count. About the only side effect from that I can recall were some low-grade headaches. The donation itself can take about eight hours or less and is fairly similar to donating blood or platelets, except for during the donation, they take blood from one arm and separate out the stem cells, then put your own blood back into your body via the other arm. So, both arms have needles in them and you cant do very much except watch movies or TV. I watched a couple of Godfather films back-to-back, and was done before we could start the third. Afterward, theres much less bodily soreness than with bone marrow, but you probably dont want to hit up the club that night.

If you think you want to get on the registry, but hip-hops not your thing, locally, GenCurehandles donor drives and recruitment for the NMDP. You can also learn more from any South Texas Blood and Tissue Center donor room.

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Why You Should Join the Bone Marrow Donor Registry

A LOCAL man on Tuesday celebrated his 39th birthday by becoming Shanghais 294th hematopoietic stem cell donor after shedding 22 kilograms to meet the eligibility requirements.

Pan Weizhong, a team leader for Sinopec, joined the China Bone Marrow Bank in 2007 after one of his colleagues successfully donated his stem cells. Last October, Pan received a call from the Shanghai Red Cross Society telling him his blood was a match for a 28-year-old woman suffering from leukemia in Wuhan, capital of central Chinas Hubei Province.

He was really excited when he found out and couldnt wait to tell me when I came home from work,Pans wife Wang Aiping, who works as an accountant at a community health care center, told Shanghai Daily yesterday.

I was also very happy because I had always supported his decision to become a donor.

But when Pan, who weighed about 90 kilograms at the time, went for a preliminary medical examination, doctors told him he had a fatty liver and needed to lose weight, Wang said.

Determined to qualify for the scheme, Pan switched to a vegetarian diet and began exercising for two hours every day. He even quit smoking and drinking alcohol, his wife said.

My son and I also became vegetarians to support him,she said.

After two months of no meat and lots of exercise, doctors gave Pan the green light.

After Tuesdays operation Pan said he was delighted to have been able to help someone he had never even met.

It feels great to celebrate my birthday by giving this woman a fresh start in life,he said.Its the best present Ive ever had.

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Man fights the flab to be cell donor -Eastday

Researchers in Bern have discovered that, during a viral infection, immune cells control the blood stem cells in the bone marrow and therefore also the body's own defenses. The findings could allow for new forms of therapy, such as for bone marrow diseases like leukemia.

During a viral infection, the body needs various defense mechanisms -- amongst other things, a large number of white blood cells (leukocytes) must be produced in the bone marrow within a short period of time. In the bone marrow, stem cells are responsible for this task: the blood stem cells. In addition to white blood cells, blood stem cells also produce red blood cells and platelets.

The blood stem cells are located in specialized niches in the bone marrow and are surrounded by specialized niche cells. During an infection, the blood stem cells must complete two tasks: they must first recognise that more blood cells have to be produced and, secondly, they must recognise what kind of.

Now, for the first time, researchers at the Department of Medical Oncology at the University of Bern and Bern University Hospital headed by Prof. Adrian Ochsenbein have investigated how the blood stem cells in the bone marrow are regulated by the immune system's so-called T killer cells during a viral infection. As this regulation mechanism mediated by the immune system also plays an important role in other diseases such as leukemia, these findings could lead to novel therapeutic approaches. The study is being published in the peer-reviewed journal "Cell Stem Cell" today.

T Killer cells trigger defenses

One function of T killer cells is to "patrol" in the blood and remove pathogen-infected cells. However, they also interact with the blood stem cells in the bone marrow. The oncologists in Bern were able to show that messenger substances secreted by the T killer cells modulate the niche cells. In turn, the niche cells control the production and also the differentiation of the blood stem cells.

This mechanism is important in order to fight pathogens such as viruses or bacteria. However, various forms of the bone marrow disease leukemia are caused by a malignant transformation of exactly these blood stem cells. This leads to the formation of so-called leukemia stem cells. In both cases, the mechanisms are similar: the "good" mechanism regulates healthy blood stem cells during an infection, whilst the "bad" one leads to the multiplication of leukemia stem cells. This in turn leads to a progression of the leukemia.

This similarity has already been investigated in a previous project by the same group of researchers. "We hope that this will enable us to better understand and fight infectious diseases as well as bone marrow diseases such as leukemia," says Carsten Riether from the Department of Clinical Research at the University of Bern and the Department of Medical Oncology at Bern University Hospital and the University of Bern.

Story Source:

The above story is based on materials provided by University of Bern. Note: Materials may be edited for content and length.

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Immune cells regulate blood stem cells, research shows

On a Saturday last September, Be the Match Foundation sponsored a 5-kilometer walk and run in Creve Coeur Park to promote donor awareness. The foundation is an international bone marrow registry, and it coordinates marrow and stem cell transplants that are used to treat blood disorders.

Mark Pearl was at the event. Two of his three kids were born with a rare blood disorder called Fanconi anemia. Alexandra was diagnosed on Christmas Day 2000. She was 5. Her younger brother, Matthew, was diagnosed shortly thereafter. A marrow donor in Sweden was quickly found for Alexandra, but no matches were found for Matthew.

Mark and his wife, Diane, began organizing donor drives. Its easy to register as a donor. A couple of swabs on the inside of a cheek to collect DNA is all that is required. At their first drive in February 2001, they registered more than 4,000 potential donors. No matches. Over the next five and a half years, they organized more than 1,000 drives and registered more than 100,000 potential donors.

A donor was eventually found in North Carolina. As is almost always the case, the donor registered at someone elses drive. Matthew received his transplant in 2006.

He and his sister are fine.

Also at the event in Creve Coeur was Brian Jakubeck. He did not know Mark, but he had registered as a potential donor at one of the drives the Pearls had organized for Matthew. One of the last drives, actually.

How did that happen? Mark has season tickets for the Rams and sits next to Ted Cassimatis, who is a college friend of Brians brother. So as the Pearls reached out well beyond their own circle of friends, Ted sent out a mass email to his friends, and that email reached Brian. He and his wife, Kathy, registered as potential donors at a drive in May 2006.

Sometime later, Brian heard the good news from Ted that a donor had been found for his friends son.

Several years passed. In August 2012, Brian heard from Be the Match. He appeared to be a match. Would he agree to have some blood samples taken to confirm that he was a match? Sure, he said.

The results were positive. He was a match. He had more tests shortly before Christmas, and in January of last year, he went to St. Louis University Hospital and gave his stem cells. This was done in a process called apheresis. It is similar to giving plasma or platelets. The blood goes through an IV, passes through a machine that collects the stem cells, and then is returned through another IV. Its painless, but takes about six hours.

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McClellan: Bone marrow registry drives often pay it forward

21 Feb 2014 20:33

Staffordshire toddler has life-saving bone marrow transplant after match is finally found

Parents of a brave toddler battling leukaemia hailed a stem-cell donor their hero as their daughter received a life-saving bone marrow transplant.

Vicky and Yaser Martini, from Essington, Staffordshire, launched a huge internet campaign to find a match for 18-month-old Margot after she was diagnosed with two types of the cancer last October.

An estimated 40,000 people have requested donor packs from charity Delete Blood Cancer since the appeal, which has been backed by celebrities Stephen Fry, Gary Barlow and former Wolves hero Steve Bull.

Margot underwent a two-hour bone marrow transplant at Great Ormond Street Hospital in London on Friday after a stem cell donor match, said to be from outside the UK, was confirmed earlier this month.

The toddler napped contentedly in her pram as the stem cells were administered via a Hickman line in her chest said dad Yaser.

This young chap has done this selfless and benevolent thing. Frankly, he is my hero, he added.

I am watching it as it happens. It is quite something.

Margot Martini, with her brothers Rufus and Oscar, her dad Yaser and mum Vicky

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Hero stem-cell donor saves brave leukaemia patient Margot Martini

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The largest ever trial of adult stem cell therapy in heart attack patients has begun at The London Chest Hospital in the UK.

Heart disease is the world's leading cause of death. Globally, more than 17 million people died from heart disease last year. In the US, over 1 million people suffer a heart attack each year, and about half of them die.

Heart attacks are usually caused by a clot in the coronary artery, which stops the supply of blood and oxygen to the heart. If the blockage is not treated within a few hours, then it causes the heart muscle to die.

The stem cell trial - titled "The effect of intracoronary reinfusion of bone marrow-derived mononuclear cells (BM-MNC) on allcause mortality in acute myocardial infarction," or "BAMI" for short - has been made possible due to a 5.9 million ($8.1 million) award from the European Commission.

The full study involves 19 partners across France, Germany, Italy, Finland, Denmark, Spain, Belgium, Poland, the Czech Republic and the UK.

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'Largest ever' trial of adult stem cells in heart attack patients begins

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20-Feb-2014

Contact: Deborah Williams-Hedges debwms@caltech.edu 626-395-3227 California Institute of Technology

In the battle against infection, immune cells are the body's offense and defensesome cells go on the attack while others block invading pathogens. It has long been known that a population of blood stem cells that resides in the bone marrow generates all of these immune cells. But most scientists have believed that blood stem cells participate in battles against infection in a delayed way, replenishing immune cells on the front line only after they become depleted.

Now, using a novel microfluidic technique, researchers at Caltech have shown that these stem cells might be more actively involved, sensing danger signals directly and quickly producing new immune cells to join the fight.

"It has been most people's belief that the bone marrow has the function of making these cells but that the response to infection is something that happens locally, at the infection site," says David Baltimore, president emeritus and the Robert Andrews Millikan Professor of Biology at Caltech. "We've shown that these bone marrow cells themselves are sensitive to infection-related molecules and that they respond very rapidly. So the bone marrow is actually set up to respond to infection."

The study, led by Jimmy Zhao, a graduate student in the UCLA-Caltech Medical Scientist Training Program, will appear in the April 3 issue of the journal Cell Stem Cell.

In the work, the researchers show that blood stem cells have all the components needed to detect an invasion and to mount an inflammatory response. They show, as others have previously, that these cells have on their surface a type of receptor called a toll-like receptor. The researchers then identify an entire internal response pathway that can translate activation of those receptors by infection-related molecules, or danger signals, into the production of cytokines, signaling molecules that can crank up immune-cell production. Interestingly, they show for the first time that the transcription factor NF-B, known to be the central organizer of the immune response to infection, is part of that response pathway.

To examine what happens to a blood stem cell once it is activated by a danger signal, the Baltimore lab teamed up with chemists from the lab of James Heath, the Elizabeth W. Gilloon Professor and professor of chemistry at Caltech. They devised a microfluidic chipprinted in flexible silicon on a glass slide, complete with input and output ports, control valves, and thousands of tiny wellsthat would enable single-cell analysis. At the bottom of each well, they attached DNA molecules in strips and introduced a flow of antibodiespathogen-targeting proteins of the immune systemthat had complementary DNA. They then added the stem cells along with infection-related molecules and incubated the whole sample. Since the antibodies were selected based on their ability to bind to certain cytokines, they specifically captured any of those cytokines released by the cells after activation. When the researchers added a secondary antibody and a dye, the cytokines lit up. "They all light up the same color, but you can tell which is which because you've attached the DNA in an orderly fashion," explains Baltimore. "So you've got both visualization and localization that tells you which molecule was secreted." In this way, they were able to measure, for example, that the cytokine IL-6 was secreted most frequentlyby 21.9 percent of the cells tested.

"The experimental challenges here were significantwe needed to isolate what are actually quite rare cells, and then measure the levels of a dozen secreted proteins from each of those cells," says Heath. "The end result was sort of like putting on a new pair of glasseswe were able to observe functional properties of these stem cells that were totally unexpected."

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A changing view of bone marrow cells

Paul Herron and Anne Hodgkinson wake up every day knowing their daughter could die.

Their 4-year-old, Katie, has cancer, and for the second time in her young life she is fighting to stay alive.

Shes scared. Shes terrified, Herron told the Star from Torontos Ronald McDonald House, where the Cambridge family is currently staying so Katie can get treatment at the Hospital for Sick Children.

For Anne and I, its been a parents worst nightmare.

When Katie was just 15 months old, she was diagnosed with acute lymphoblastic leukemia. But after 25 months of intensive treatment, including lumbar punctures, bone marrow aspirations, chemotherapy and steroids, Katie fought the cancer into remission.

Finally, the family thought, they could say goodbye to hospital beds and the hours spent pacing hallways waiting for results. Finally, they could be normal.

But last November, the life they had built for themselves crumbled once again. The cancer was back, and this time Katie would need a stem cell donor.

The first time, we never made it public. We kept to ourselves, said Herron. But because this time she needs a stem cell donation, we had to get the word out.

No one in the family is a match, and the national registry has yet to turn up a name. This Saturday, Katies supporters will host a stem cell donor clinic at the Cambridge Sports Park from 1 to 5 p.m. All thats required for testing is a cheek swab.

(Stem cells are collected from a matching donors bone marrow or blood after the donor has given informed consent and undergone medical tests to encourage good health and compatibility.)

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Stem cell donor clinic planned for 4-year-old battling leukemia again

Raleigh, NC (PRWEB) February 20, 2014

A study published in the journal Theranostics and reported by the Non-Hodgkins Lymphoma Center finds that a class of drugs that stimulate stem cell production in patients and donors is safe to use.

The drugs are biologically similar to granulocyte colony stimulating factor (G-CSF), a human glycoprotein that stimulates the bone marrow to produce granulocytes (a type of white blood cell) and stem cells and release them into the bloodstream. The drugs can be given to patients with diseases like Non-Hodgkins Lymphoma to stimulate the release of their own stem cells, or to donors for transplantation into sick patients.

Since the patent on G-CSF expired, several companies have begun producing these drugs. Referred to as biosimilars in Europe and follow-on biologics in the US, several have been approved for use, although their safety and efficacy is still being debated.

The new study examines published reports on more than 900 patients with Non-Hodgkins Lymphoma or another blood cancer and healthy stem cell donors treated with the G-CSF biosimilar compounds Ratiograstim, Tevagrastim or Zarzio. The researchers report that the drugs produced good mobilization of CD34+ stem cells and produced side effects similar to the original G-CSF. Once the collected stem cells were grafted into a new host, they behaved comparably to stem cells stimulated by G-CSF.

In summary, the efficacy of biosimilar G-CSFs in terms of peripheral blood hematopoietic stem cell yield as well as their toxicity profile are equivalent to historical data with reference to G-CSF, the researchers write in the European medical journal Theranostics. (Schmitt, M, et al, Biosimilar G-CSF Based Mobilization of Peripheral Blood Hematopoietic Stem Cells for Autologous and Allogeneic Stem Cell Transplantation, January 23, 2014, Theranostics, pp. 280-289. http://www.ncbi.nlm.nih.gov/pubmed/24505236)

Non-Hodgkins Lymphomas include cancers that involve the lymphocytes or white blood cells. They account for about 4 percent of all new cancer cases in the U.S. The National Cancer Institute estimates that more than 500,000 Americans are currently living with Non-Hodgkins Lymphoma. Today, there is more interest on the causes of Non-Hodgkins Lymphoma.

The Non-Hodgkins Lymphoma Center is part of the Cancer Monthly organization. The Non-Hodgkins Lymphoma Center has been established by Cancer Monthly to provide more comprehensive information on the causes, diagnosis, and treatments for the many different subtypes of Non-Hodgkins Lymphoma. For over ten years, Cancer Monthly has been the only centralized source of cancer treatment results. Patients can see the actual survival rate, quality-of-life indicators, and other key data for approximately 1,500 different cancer treatments. Cancer Monthly provides timely and ground-breaking news on the causes, diagnoses and treatments of the most common cancers including Bladder, Brain, Breast, Colon, Kidney (Renal), Liver, Lung (NSCLC), Ovarian, Prostate, and Rectal Cancers, Melanoma, Mesothelioma, and Non-Hodgkin's Lymphoma. Written for patients and their loved ones, Cancer Monthly helps families make more informed treatment decisions.

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Study Finds Biosimilar Compounds Safe and Effective for Non-Hodgkins Lymphoma, According to the Non-Hodgkins ...

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A MOTHER whose son successfully battled a brain tumour but was later diagnosed with leukaemia is starting a campaign to encourage people to donate their stem cells.

Andrea Poyser's son Laughlin known as Lockey Whiteley, 7, had a brain tumour removed in 2011. But he was then diagnosed with treatment-related acute myeloid leukaemia (AML) last November.

Since then, the Burnham family has spent countless hours travelling to and from London's Great Ormond Street Hospital for Lockey's treatment.

Now Andrea, 42, with the help of friends, has set up "Unlock a Life for LocKEY", which aims to help raise awareness about stem cell donations.

"The general public think that stem cells come from the bone marrow and that's just not true," said the former drama teacher and actress Andrea.

"It's such a simple and easy procedure that costs nothing you can really make a difference to the lives of children. If you can, then why not.

"There are people suffering that could die because of lack of stem cells, it's easy to find out if you're a match and it's possible that you could save someone's life."

The group hope to help unlock matches for stem cell donors, plus give advice and support to families with children who have been diagnosed with leukaemia.

Unlock a Life for LocKEY is organising an event on Saturday, March 1, in Burnham where people can submit swab tests and donate during a day of live entertainment with a number of celebrities in attendance.

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Maldon Chronicle published Donate your stem cells: Mother's campaign after son Lockey, 7,...

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Affordable Care Act Updates: CBSPittsburgh.com/ACA

Health News & Information: CBSPittsburgh.com/Health

PITTSBURGH (KDKA) After injuries from gymnastics and dance when she was younger, Linda Morning-Starpoole was having terrible knee pain.

Sitting and standing up and getting up and moving, Linda said.

The news from her orthopedic surgeon was not encouraging.

I was sent off with a prescription, and basically said, take this, and when it gets so bad, well take out your knees. And that was really upsetting to me. It was such an ugly picture that was painted for my future, Linda said.

Traditional treatment might involve steroid injections, physical therapy, and joint replacement.

But Linda wanted an alternative. When she first heard about using stem cell injections, she was very intrigued.

The thought of me healing me with my own self is what sold me on the procedure, Linda said.

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Stem Cells Being Used To Treat Knee, Joint Pain

by GEORGE RIBA

WFAA Sports

Posted on February 18, 2014 at 12:41 PM

DALLAS -- Malena Brownwas hoping for a match onValentines Day weekend, butnot the kind of match you expect.

The 15-year-old daughter of Dallas Cowboys running backs coach Gary Brown is looking for an "angel donor" whose bone marrow stem cells will match hers and help her overcome what's known as CML, or chronic myeloid leukemia.

Well, its kind of scary knowing that there wasn't a match for me, but we're doing a bone marrow drive now and hopefully find somebody that matches me, Malena said.

Neither one of Malena's siblings is a match, and trying to find one has become a challenge.

The No. 1 challenge has been trying to find a match based on her ancestry, and she being biracial, has been extra difficult because the registry is under-represented with African-American and other multiracial people, said Kim Brown, Malenas mother.

We've had nothing but people trying to help us in any way they can, said father Gary Brown. When you know your daughter is going through something hard, and there are other people out there that care as much as you do and want to help her as much as you do.

To add your name to the national registry, all you do is a simple swab test, add it to a booklet, and send it in.

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Cowboys coach seeks marrow match for daughter

by GEORGE RIBA

WFAA Sports

Posted on February 15, 2014 at 10:35 AM

DALLAS Malena Brown is hoping for a match on this Valentines Day weekend, but its not the kind of match you expect.

The 15-year-old daughter of Dallas Cowboys running backs coach Gary Brown is looking for an "angel donor" whose bone marrow stem cells will match hers and help her overcome what's known as CML, or chronic myeloid leukemia.

Well, its kind of scary knowing that there wasn't a match for me, but we're doing a bone marrow drive now and hopefully find somebody that matches me, Malena said.

Neither one of Malena's siblings is a match, and trying to find one has become a challenge.

The No. 1 challenge has been trying to find a match based on her ancestry, and she being biracial, has been extra difficult because the registry is under-represented with African-American and other multiracial people, said Kim Brown, Malenas mother.

We've had nothing but people trying to help us in any way they can, said father Gary Brown. When you know your daughter is going through something hard, and there are other people out there that care as much as you do and want to help her as much as you do.

To add your name to the national registry, all you do is a simple swab test, add it to a booklet, and send it in.

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Cowboys coach seeks marrow match for teen daughter