PUBLIC RELEASE DATE:

11-Mar-2014

Contact: Karen Richardson krchrdsn@wakehealth.edu 336-716-4453 Wake Forest Baptist Medical Center

WINSTON-SALEM, N.C. March 11, 2014 Discovering where a common virus hides in the body has been a long-term quest for scientists. Up to 80 percent of adults harbor the human cytomegalovirus (HCMV), which can cause severe illness and death in people with weakened immune systems.

Now, researchers at Wake Forest Baptist Medical Center's Institute for Regenerative Medicine report that stem cells that encircle blood vessels can be a hiding place, suggesting a potential treatment target.

In the American Journal of Transplantation (online ahead of print), senior scientist Graca Almeida-Porada, M.D., Ph.D., professor of regenerative medicine at Wake Forest Baptist, and colleagues report that perivascular stem cells, which are found in bone marrow and surround blood vessels in the body's organs, are a reservoir of HCMV.

The virus, which is part of the herpes family, is unnoticed in healthy people. Half to 80 percent of all adults in the U.S. are infected with HCMV, according to the Centers for Disease Control and Prevention. In people with weakened immune systems, including those with HIV, undergoing chemotherapy, or who are organ or bone marrow transplant recipients, the virus can become re-activated.

Once re-activated, HCMV can cause a host of problems from pneumonia to inflammation of the liver and brain that are associated with organ rejection and death.

"There are anti-viral medications designed to prevent HCMV from re-activating, but HVMC infection remains one of the major complications after both organ and bone marrow transplants," said Almeida-Porada. "The question scientists have been asking for years is, 'Where does the virus hide when it is latent?' Maybe if we knew, we could target it."

Scientists have previously shown that one hiding place is hematopoietic stem cells, which give rise to blood cells. "There has been research on and off looking for the other hiding places," said Almeida-Porada. "Identifying the cells that can harbor the virus and are responsible for its re-activation could potentially lead to development of novel targeted therapies."

Originally posted here:
Finding hiding place of virus could lead to new treatments

The parents of a 2-year-old Pasadena girl who was diagnosed with an aggressive form of leukemia were this week renewing calls for help in their search for a bone marrow donor after stem cells donated from the girls father failed to help.

Sofia Flores, shown in a family photo, needs a bone marrow donor.

Sofia Flores story first came to light in October 2013 when her parents asked for help in finding a bone marrow donor for their daughter.

Sofia needed a marrow transplant to combat acute myeloid leukemia, according to A3M, a Los Angeles nonprofit that is helping Sofias parents seek a match for the little girl.

However, after an extensive search, no match was found.

On Jan. 23, her father donated his stem cells to her, which was the only alternative available at the time, according to Erica Westfall, Sofias mother.

But the treatment was not successful and Sofias cancer relapsed.

Sofias last chance for survival would be a transplant from an unrelated donor in the next two months, according to her mother.

Weve been searching for a bone marrow match even harder because this is her last chance, her father Ignacio Flores said in a video released to news media on Monday.

Sofia has not found a donor through the Be the Match registry, in part because her mixed-race ethnicity makes it difficult to find a compatible donor, according to A3M. Sofia is half white and half Mexican.

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Father of 2-Year-Old in Need of Bone Marrow: This Is Her Last Chance

The recent news of veteran TV journalist Tom Brokaw being diagnosed with multiple myeloma sparked interest in this rare form of cancer. Approximately 20,000 people are diagnosed annually with multiple myeloma cancer of the plasma cells in the bodys bone marrow. These abnormal plasma cells dont produce antibodies, so the immune system cant fight off infections.

Like Brokaw, who is 74, the majority of people diagnosed with multiple myeloma as well as more common blood cancers such as leukemia and lymphoma are older than 65. That means that many of these patients depend on Medicare to pay for their treatment, which often includes a blood or bone marrow transplant (BMT).

Ten years ago, patients older than 55 were commonly excluded from this treatment option. Today, because of medical advances, the Medicare population is the fastest-growing segment of patients in most BMT programs in the United States.

However, because of Medicare coverage restrictions, many patients who need a transplant are unable to receive treatment unless they are in the financial position to pay privately for their care.

The financial burden is even more significant when a transplant requires the use of donated stem cells, often needed for those with blood cancers such as leukemia and lymphoma. Because of a difference in the way that Medicare reimburses hospitals for BMT in comparison with solid organ transplantation, each BMT using donor cells results in a substantial financial loss to the hospital providing care.

The financial loss per transplant case is large enough that it is unsustainable, cannot be offset by private insurance payments and is threatening our ability to continue to deliver this vital therapy to those who need it most.

Our clinical success in finding ways to treat older patients has created an unfortunate, but very real, financial threat to the continued existence of our field. In December, we began a dialogue with our partners at Medicare to remedy this situation and hope that continued discussions will result in a correction of the rate-setting methodology currently used.

We are mindful that BMT is an expensive therapy. There is no question that expert teams and significant resources are required. But it is also a lifesaving therapy. Currently, there are more than 100,000 transplant survivors in the United States. With continuing advances in the use of transplant, we project 250,000 by 2020 and 500,000 by 2030 with a quarter of the survivors being over 60 years old.

These costs would not disappear if this treatment were not available. The costs of providing alternate therapies that do not have the potential to be curative are significant. Older patients deserve continued access to therapies that will provide them with the best chance of enjoying more well-earned years of high-quality life with their families and friends.

This month, the American Society for Blood and Marrow Transplantation (ASBMT) celebrates 20 years since its founding. We represent nearly 2,000 transplant clinicians and health care professionals worldwide. Recently we gathered in Dallas for our annual meeting to share cutting-edge research and knowledge, continuing our quest to be the best in the world at what we do for the sake of our patients.

Read the original here:
Blood, marrow transplants must be kept accessible

4 hours ago This photo shows Dr. Sean Morrison, Director of the Children's Research Institute and senior author of the study, right, and Dr. Robert A.J. Signer, a postdoctoral research fellow and the study's first author. Credit: University of Texas Southwestern Medical Center

For the first time, researchers have shown that an essential biological process known as protein synthesis can be studied in adult stem cells something scientists have long struggled to accomplish. The groundbreaking findings from the Children's Medical Center Research Institute at UT Southwestern (CRI) also demonstrate that the precise amount of protein produced by blood-forming stem cells is crucial to their function.

The discovery, published online today in Nature, measures protein production, a process known as translation, and shows that protein synthesis is not only fundamental to how stem cells are regulated, but also is critical to their regenerative potential.

"We unveiled new areas of cellular biology that no one has seen before," said Dr. Sean Morrison, Director of the Children's Research Institute, Professor of Pediatrics, and the Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern Medical Center. "No one has ever studied protein synthesis in somatic stem cells. This finding not only tells us something new about stem cell regulation, but opens up the ability to study differences in protein synthesis between many kinds of cells in the body. We believe there is an undiscovered world of biology that allows different kinds of cells to synthesize protein at different rates and in different ways, and that those differences are important for cellular survival."

Dr. Adrian Salic's laboratory at Harvard Medical School chemically modified the antibiotic puromycin in a way that made it possible to visualize and quantify the amount of protein synthesized by individual cells within the body. Dr. Robert A.J. Signer, a postdoctoral research fellow in Dr. Morrison's laboratory and first author of the study, realized that this reagent could be adapted to measure new protein synthesis by stem cells and other cells in the blood-forming system.

What they came across was astonishing, Dr. Morrison said. The findings suggested that different types of blood cells produce vastly different amounts of protein per hour, and stem cells in particular synthesize much less protein than any other blood-forming cells.

"This result suggests that blood-forming stem cells require a lower rate of protein synthesis as compared to other blood-forming cells," said Dr. Morrison, the paper's senior author.

Researchers applied the findings to a mouse model with a genetic mutation in a component of the ribosome the machinery that makes proteins and the rate of protein production was reduced in stem cells by 30 percent. The scientists also increased the rate of protein synthesis by deleting the tumor suppressor gene Pten in blood-forming stem cells. In both instances, stem cell function was noticeably impaired.

Together, these observations demonstrate that blood-forming stem cells require a highly regulated rate of protein synthesis, such that increases or decreases in that rate impair stem cell function.

"Amazingly, when the ribosomal mutant mice and the Pten mutant mice were bred together, stem cell function returned to normal, and we greatly delayed, and in some instances entirely blocked, the development of leukemia," Dr. Morrison said. "All of this happened because protein production in stem cells was returned to normal. It was as if two wrongs made a right."

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Stem cell study opens door to undiscovered world of biology

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Newswise SEATTLE The Fred Hutchinson Bone Marrow Transplant Program at Seattle Cancer Care Alliance (SCCA) was recently recognized by the Center for International Blood and Marrow Transplant Research (CIBMTR) for outperforming its expected one-year survival rate for allogeneic transplant patients. The results published by the CIBMTR, analyzed the National Marrow Donor Programs (NMDP) registry of 168 U.S. transplant centers over a three-year period for its 2013 Transplant Center-Specific Survival Report.

The Fred Hutchinson Bone Marrow Transplant Program at SCCA pioneered the clinical use of bone marrow and stem cell transplantation more than 40 years ago and have performed more than 14,000 bone marrow transplants more than any other institution in the world. Today, the organization is one of just 13 stem cell transplant programs nationwide that exceeded its anticipated one-year survival rate for patients undergoing allogeneic transplants.

This type of transplant uses stem cells from a donor who may or may not be related to the patient. Stem cell transplants, including bone marrow transplants, are used to treat a range of leukemias and lymphomas, as well as other diseases such as severe aplastic anemia and sickle cell disease.

Comparing Transplant Centers

Comparing transplant centers in the U.S. is an extremely challenging process, explains Dr. Marco Mielcarek, medical director of the Adult Blood and Marrow Transplant Program at SCCA. There are so many variables that must be taken into account, including type of cancer and stage, the patients underlying medical problems and age, the type of transplant they undergo, and the source of the stem cells for the transplant. Each patient has a unique risk profile.

Although the process of comparing transplant centers can be challenging, the intensive analysis allows researchers to compare themselves to other centers, leading to improved outcomes. Additionally, the report provides patients and their families with valuable information necessary when evaluating where to go for treatment.

When you adjust for risk factors, our patients outcomes exceeded expectations over a three-year period, Dr. Mielcarek says, thats information that is helpful for patients to know when they are making important health care decisions with their families.

To arrive at its findings, CIBMTR independently examined the survival rates of 19,945 transplants performed to treat blood cancers at U.S. centers in the NMDP network. The most recent reporting period covered January 1, 2009 to December 31, 2011. During this three-year period, 762 allogeneic transplants were performed at SCCA. The report, published annually, is required by federal law and is designed to provide potential stem cell transplant recipients, their families, and the public with comparative survival rates among transplant centers.

Read the rest here:
Bone Marrow Transplant Program at Seattle Cancer Care Alliance Recognized for Its One-Year Survival Rates

The approach involves using enzymes to destroy a gene in the immune cells of people with HIV, thereby increasing resistance to the virus

Scanning electron micrograph of a human T cell from the immune system of a healthy donor. Credit:NIAID/NIH - Wikimedia Commons

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. The findings were published March 5 in The New England Journal of Medicine.

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 thatBrown gained the ability to control his HIV infectionafter they treated him with donor bone-marrow stem cells that carried a mutation in a gene calledCCR5. Most HIV strains use a protein encoded byCCR5as 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 isnot 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 beneficialCCR5 mutation in a persons own cells, using targeted gene editing.

Personalized medicine 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 theCCR5gene 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 functionalCCR5gene, 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?

Long-term action 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 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.

Originally posted here:
Gene-Editing Technique Shown to Work as HIV Treatment

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Some professional athletes' enthusiasm for certain stem cell treatments outpaces the evidence

Peter Ryan

In 2005, at the age of 32, then Los Angeles Angel Bartolo Coln won the American League Cy Young Award for best pitcher, one of professional baseball's top honors. He stumbled through subsequent seasons, however, after a series of rips and strains in the tendons and ligaments of his throwing arm, shoulder and back. In 2009 he all but quit baseball. Desperate to reclaim his career, Coln flew home to the Dominican Republic in 2010 for an experimental procedure not vetted or approved by the U.S. Food and Drug Administration. Doctors centrifuged samples of Coln's bone marrow and fat, skimmed off a slurry containing a particular kind of stem cellimmature, self-renewing cells that can turn into a variety of tissuesand injected it into his injured shoulder and elbow. Within months of the procedure the then 37-year-old Coln was once again pitching near the top of his game for the New York Yankeescommanding a 93-mile-per-hour fastball.

Whether the injected stem cells rejuvenated his arm is an open question. The fda and the International Society for Stem Cell Research warn that no rigorous studies have demonstrated that such treatments safely and effectively repair damaged connective tissue in people. The results of related animal studies, though promising, have raised more questions than answers. The term stem cell makes it sound cutting edge and exciting, says Paul Knoepfler, a cell biologist at the University of California, Davis, who also writes frequently on policy surrounding stem cells. But the role of these cells in sports medicine is essentially all hype.

No matter, apparently, to the aging, injured athletes who have followed Coln's lead. Lefty pitcher C. J. Nitkowski, who underwent the same procedure in 2011, told readers of his personal blog that he did not mind the lack of carefully controlled research. My attitude is I don't have the time to wait for the five- or 10-year study to come out, the then 38-year-old relief pitcher wrote, so I'm taking a chance now. Besides, Nitkowski figured, even if the treatment did not work, any health risks ought to be slight because the cells involved were his own.

That might not be such a safe bet. Numerous studies suggest that Coln, Nitkowski and others trying untested stem cell treatments may be risking more than they think. Even a syringe of one's own stem cells taken from one part of the body and squirted into another may multiply, form tumors, or may leave the site you put them in and migrate somewhere else the fda warns on its Web site. More clinical research is needed to define safety procedures, as well as how many cells of which types and what other tissue factors produce the desired results. In some animal studies, for example, the regenerated tissue is not as strong or flexible as the original. In other cases, an overgrowth of scar tissue makes the injected tendon or ligament adhere to the overlying skin. By preventing different tissues from gracefully sliding past one another, these adhesions sometimes pull an even bigger tear in an already serious wound.

In addition, Knoepfler worries that high-profile sports testimonials by Coln, Nitkowski and others will encourage joggers with blown-out knees and the parents of sore-armed Little Leaguers to demand the procedure before it has been thoroughly tested. When celebrities take to a new treatment, many other people follow suit, he says. Such premature enthusiasmor an unforeseen tragedy that results from proceeding too fast too sooncould also prevent serious researchers from getting funding to do the kinds of careful experiments that might eventually lead to safe and reliable treatments.

Seeds of Repair

The need for better ways to reknit damaged tendons and ligaments is painfully apparent to the roughly two million Americans in a given year who seek medical help for tears in their shoulder's rotator cuff, for example, or the 100,000 patients in the same year who undergo surgery in the U.S. to repair a ripped or ruptured anterior cruciate ligament (ACL) of the knee. Tendons and ligaments are tough, fibrous bands, made mostly of collagen, that anchor networks of muscles to a bone or link bones and cartilage across crucial joints. They lend strength, flexibility and stability to your daily twists and turns, whether you are rocketing a baseball across home plate or hefting a suitcase into an overhead bin. Once frayed or snapped, they can take many months or longer to mendeven with surgery.

Read more from the original source:
A Dangerous Game: Some Athletes Risk Untested Stem Cell Treatments

14 hours ago This is Kevin Kit Parker, the Thomas D. Cabot Associate Professor of Applied Science and Associate Professor of Biomedical Engineering, and Harvard Stem Cell Institute Principal Faculty member, has identified standards making it possible to quantitatively judge and compare commercially available stem cell lines. Credit: Jon Chase/Harvard Staff Photographer

After more than a decade of incremental and paradigm shifting, advances in stem cell biology, almost anyone with a basic understanding of life sciences knows that stem cells are the basic form of cell from which all specialized cells, and eventually organs and body parts, derive.

But what makes a "good" stem cell, one that can reliably be used in drug development, and for disease study? Researchers have made enormous strides in understanding the process of cellular reprogramming, and how and why stem cells commit to becoming various types of adult cells. But until now, there have been no standards, no criteria, by which to test these ubiquitous cells for their ability to faithfully adopt characteristics that make them suitable substitutes for patients for drug testing. And the need for such quality control standards becomes ever more critical as industry looks toward manufacturing products and treatments using stem cells.

Now a research team lead by Kevin Kit Parker, a Harvard Stem Cell Institute (HSCI) Principal Faculty member has identified a set of 64 crucial parameters from more than 1,000 by which to judge stem cell-derived cardiac myocytes, making it possible for perhaps the first time for scientists and pharmaceutical companies to quantitatively judge and compare the value of the countless commercially available lines of stem cells.

"We have an entire industry without a single quality control standard," said Parker, the Tarr Family Professor of Bioengineering and Applied Physics in Harvard's School of Engineering and Applied Sciences, and a Core Member of the Wyss Institute for Biologically Inspired Engineering.

HSCI Co-director Doug Melton, who also is co-chair of Harvard's Department of Stem Cell and Regenerative Biology, called the standard-setting study "very important. This addresses a critical issue," Melton said. "It provides a standardized method to test whether differentiated cells, produced from stem cells, have the properties needed to function. This approach provides a standard for the field to move toward reproducible tests for cell function, an important precursor to getting cells into patients or using them for drug screening."

Parker said that starting in 2009, he and Sean P. Sheehy, a graduate student in Parker's lab and the first author on a paper just given early on-line release by the journal Stem Cell Reports, "visited a lot of these companies (commercially producing stem cells), and I'd never seen a dedicated quality control department, never saw a separate effort for quality control." Parker explained many companies seemed to assume that it was sufficient simply to produce beating cardiac cells from stem cells, without asking any deeper questions about their functions and quality.

"We put out a call to different companies in 2010 asking for cells to start testing," Parker says, "some we got were so bad we couldn't even get a baseline curve on them; we couldn't even do a calibration on them."

Brock Reeve, Executive Director of HSCI, noted that "this kind of work is as essential for HSCI to be leading in as regenerative biology and medicine, because the faster we can help develop reliable, reproducible standards against which cells can be tested, the faster drugs can be moved into the clinic and the manufacturing process."

The quality of available human stem cells varied so widely, even within a given batch, that the only way to conduct a scientifically accurate study, and establish standards, "was to use mouse stem cells," Parker said, explaining that his group was given mouse cardiac progenitor cells by the company Axiogenesis.

Continued here:
Establishing standards where none exist: Researchers define 'good' stem cells

BOSTON -

A bone marrow transplant could be a life-saving move for a little girl from Chester.

Keith McGilvery visited her at Boston Children's Hospital Tuesday and found out she's not the only young Vermonter who's sick on her floor. There are two kids from Vermont-- one from Chester and the other from Colchester. They're neighbors at Children's Hospital hoping that their transplants will make them better.

Tuesday, we visited Lindsey Sturtevant, she's the 12-year-old who just received a second bone marrow transplant to fight off a pre-leukemia condition that's done a number on her blood cells.

During our visit, we learned that Colchester Middle Schooler Le'Ondre Brockington is in the hospital bed next door. The 13-year old is fighting a rare form of acute myeloid leukemia. He's been in the hospital for seven months and his mom says every day has been a battle. Both families are thankful to their transplants.

Lindsey's doctor, Christine Duncan of the Dana-Farber Cancer Institute and Boston Children's Hospital, talked with us about what's involved if you decide to donate.

"There are lots of different ways that we collect stem cells. Some are directly from the bone, some are from your blood, most often it is a blood-type donation. For people that are really interested, they can look at the national marrow donor program which is the program that helped us find a donor for Lindsey," Dr. Duncan said.

Matches don't always come from family; Lindsey's first donor came from a 42-year-old woman in Europe and the second came from a 23-year-old man.

Le'Ondre's bone marrow donation came from a 33-year-old man.

For more information on becoming a donor:

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Sick Vt. kids highlight need for bone marrow donors

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.

Read this article:
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.

Read more:
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.

Go here to read the rest:
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 ...

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.

Here is the original post:
Chennai TOSH hospital treats knee arthritis with stem cells

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.

Originally posted here:
Local Weather

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.

Read more from the original source:
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.

Visit link:
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