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Archive for the ‘Bone Marrow Stem Cells’ Category

Opening-up the stem cell niche: Hematopoietic stem cell transplantation without irradiation

For many years scientists have been trying to unravel mechanisms that guide function and differentiation of blood stem cells, those cells that generate all blood cells including our immune system. The study of human blood stem cells is difficult because they can only be found in the bone marrow in specialized "niches" that cannot be recapitulated in a culture dish. Now a group of scientists from Dresden led by stem cell researcher Prof. Claudia Waskow (Technische Universitt Dresden) was able to generate a mouse model that supports the transplantation of human blood stem cells despite the species barrier and without the need for irradiation. They used a mutation of the Kit receptor in the mouse stem cells to facilitate the engraftment of human cells.

In the new model human blood stem cells can expand and differentiate into all cell types of the blood without any additional treatment. Even cells of the innate immune system that can normally not be found in "humanized" mice were efficiently generated in this mouse. Of significance is the fact that the stem cells can be maintained in the mouse over a longer period of time compared to previously existing mouse models. These results were now published in the journal Cell Stem Cell.

"Our goal was to develop an optimal model for the transplantation and study of human blood stem cells," says Claudia Waskow, who recently took office of the professorship for "animal models in hematopoiesis" at the medical faculty of the TU Dresden. Before, Prof. Waskow was a group leader at the DFG-Center for Regenerative Therapies Dresden where most of the study was conducted.

The trick used by Claudia Waskow's team to achieve optimal stem cell engraftment was the introduction of a naturally occurring mutation of the Kit receptor into mice that lack a functional immune system. This way they circumvented the two major obstacles of blood stem cell transplantation: the rejection by the recipient's immune system and absence of free niche space for the incoming donor stem cells in the recipient's bone marrow. Space is usually provided by irradiation therapy, called conditioning, because it damages and depletes the endogenous stem cells and thus frees space for the incoming human cells. However, irradiation is toxic to many cell types and can lead to strong side effects. The Kit mutation in the new mouse model impairs the recipient's stem cell compartment in such a way that the endogenous blood stem cells can be easily replaced by human donor stem cells with a functional Kit receptor. This replacement works so efficiently that irradiation can be completely omitted allowing the study of human blood development in a physiological setting. The model can now be used to study diseases of the human blood and immune system or to test new treatment options.

The results from Prof. Waskow's group also show that the Kit receptor is important for the function of human blood stem cells, notably in a transplantation setting. Further studies will now focus on using this knowledge about the role of the receptor to improve conditioning therapy in the setting of therapeutic hematopoietic stem cell transplantation in patients.

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The above story is based on materials provided by Technische Universitt Dresden. Note: Materials may be edited for content and length.

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Opening-up the stem cell niche: Hematopoietic stem cell transplantation without irradiation

Citalopram increases the differentiation efficacy of BMSCs into neuronal-like cells

PUBLIC RELEASE DATE:

10-Jul-2014

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research

There is evidence that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. Dr. Javad Verdi and his team, Tehran University of Medical Sciences, Iran proposed that citalopram, a selective serotonin reuptake inhibitor, can increase the efficacy of bone marrow mesenchymal stem cells (BMSCs) differentiating into neuronal-like cells. Experimental results confirmed that citalopram can improve the neuronal-like cell differentiation of BMSCs by increasing cell proliferation and survival while maintaining their neuronal characteristics. These results were published in Neural Regeneration Research (Vol. 9, No. 8, 2014).

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Article: "Citalopram increases the differentiation efficacy of bone marrow mesenchymal stem cells into neuronal-like cells" by Javad Verdi1, 2, Seyed Abdolreza Mortazavi-Tabatabaei1, 2, Shiva Sharif 2, 3, Hadi Verdi2, Alireza Shoae-Hassani1, 2 (1 Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2 Department of Stem Cells and Tissue Engineering, Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3 Department of Tissue Engineering, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran)

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Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research http://www.nrronline.org/

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Citalopram increases the differentiation efficacy of BMSCs into neuronal-like cells

Cindy Crawford Is Helping a 2-Year-Old Boy Find a Bone Marrow Donor

Update

By K.C. Baker

07/10/2014 at 11:30 AM EDT

Cindy Crawford and Chase Foley

Splash News Online; Courtesy Chase Foley

When Cindy Crawford found out about a 2-year-old boy with leukemia who needed a bone marrow transplant to save his life, she had to do something to help.

"I lost my little brother, Jeff, to leukemia when I was just 10 years old," Crawford, 48, tells PEOPLE. "Sadly, a bone marrow transplant wasn't an option for him then."

In 1974, when Crawford was 8 years old, Jeff was diagnosed with acute lymphoblastic leukemia. He was just 2 years old. At the time, she says, the deadly disease only had a 25 percent cure rate. After two years of experimental treatments, Jeff lost his battle, right before his 4th birthday.

The death of her brother, whom she describes as "one of the most influential people in my life," was devastating, says Crawford, who for years has been an advocate for bone marrow donation.

"But today," Crawford explains, "we have the chance to save the life of little Chase Foley and countless other children. We need your help to find him a bone marrow donor."

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Cindy Crawford Is Helping a 2-Year-Old Boy Find a Bone Marrow Donor

Sarasota Stem Cell Specialist Inject Knees for Bone on Bone as alliterative – Video


Sarasota Stem Cell Specialist Inject Knees for Bone on Bone as alliterative
http//:Geckojoiontandspine.com Using adipose and bone marrow stem cells combined as well as PRP or the growth factors from the blood she was able to avoid a ...

By: AskDoctorJL

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Sarasota Stem Cell Specialist Inject Knees for Bone on Bone as alliterative - Video

Stem cell treatment causes nasal growth in woman's back

A woman in the US has developed a tumour-like growth eight years after a stem cell treatment to cure her paralysis failed. There have been a handful of cases of stem cell treatments causing growths but this appears to be the first in which the treatment was given at a Western hospital as part of an approved clinical trial.

At a hospital in Portugal, the unnamed woman, a US citizen, had tissue containing olfactory stem cells taken from her nose and implanted in her spine. The hope was that these cells would develop into neural cells and help repair the nerve damage to the woman's spine. The treatment did not work far from it. Last year the woman, then 28, underwent surgery because of worsening pain at the implant site.

The surgeons removed a 3-centimetre-long growth, which was found to be mainly nasal tissue, as well as bits of bone and tiny nerve branches that had not connected with the spinal nerves.

The growth wasn't cancerous, but it was secreting a "thick copious mucus-like material", which is probably why it was pressing painfully on her spine, says Brian Dlouhy at the University of Iowa Hospitals and Clinics in Iowa City, the neurosurgeon who removed the growth. The results of the surgery have now been published.

"It is sobering," says George Daley, a stem cell researcher at Harvard Medical School who has helped write guidelines for people considering stem cell treatments. "It speaks directly to how primitive our state of knowledge is about how cells integrate and divide and expand. "

The case shows that even when carried out at mainstream hospitals, experimental stem cell therapies can have unpredictable consequences, says Alexey Bersenev, a stem cell research analyst who blogs at Cell Trials. "We have to realise complications can also happen in a clinical trial," he says.

Stem cells have the prized ability to divide and replenish themselves, as well as turn into different types of tissues. There are several different stem cells, including ones obtained from an early embryo, aborted fetuses, and umbilical cord blood. There are many sources within adult tissues, too, including bone marrow.

While often hailed as the future of medicine, stem cells' ability to proliferate carries an inherent danger and the fear has always been that when implanted into a person they could turn cancerous.

Still, a few stem cell therapies have now been approved, such as a treatment available in India that takes stem cells from the patient's eye in order to regrow the surface of their cornea, and a US product based on other people's bone stem cells.

Many groups around the world are investigating a wide range of other applications, including treating heart attacks, blindness, Parkinson's disease and cancer. Research groups at universities and hospitals need to meet strict safety guidelines for clinical trials but some small private clinics are offering therapies to people without research or marketing approval. There is a growing number of lawsuits against such clinics and a few cases have been reported of tumours or excessive tissue growth (see "Ongoing stem cell trials" below).

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Stem cell treatment causes nasal growth in woman's back

Brown University Researchers Discover Chemo Resistant Stem Cells

By Marcus Johnson

Researchers at Brown University have found that adipose-derived human stem cells (ASCs) might be highly resistant to methotrexate (MTX), a common chemotherapy drug. ASCs can ultimately become bone and other vital tissues throughout the body, which could be key for researchers looking to protect bone tissue from the damage caused by MTX treatment. MTX, which is used to treat a number of different cancers including acute lymphoblastic leukemia, causes the loss of bone density and has an adverse effect on bone marrow derived stem cells.

Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs, said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldnt have these issues.

Beane examined how MTX affects stem cells and certain tissues in the body and said that the resistance of certain stem cells to the drugs toxicity could mean new possibilities in the drug development realm. The researchers are now looking to find a way to make their study practical for doctors that are treating patients suffering from cancer. The next step is to test ASC survival in animal trials, where researchers will determine how the cells fare in mice that are also hit with the chemotherapy drug.

The study was published in the journal, Experimental Cell Research.

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Brown University Researchers Discover Chemo Resistant Stem Cells

The promise and hazards of stem cell research

Federal funding blocked mainly over opposition to use of blastocysts

PORTSMOUTH Dr. Amy Sievers, an oncologist at Portsmouth Regional Hospital, does stem cell transplants with great success for her patients and is a firm advocate for stem cell research.

Sievers is allowed to do stem cell blood transplants because she does not use the source of controversy, embryonic stem cells. Instead, she can use stem cells from bone marrow, where blood is made. The cells can become new blood for transfusion into patients with blood-related cancers like leukemia.

"When we get past the chemo and radiation, the hope is we can replace blood and give the patient healthy blood and a chance to build a good immune system," Sievers said.

Parents saving cord blood when they give birth is an option, but Dr. Alexandra Bonesho of Core Physicians in Epping said it is very costly for the patient, is not covered by insurance and is not something pediatricians recommend widely unless there is a reason.

"It's not something we use as a practical course of events," Bonesho said. "Cord blood banking is very expensive, less so if the blood stem cells are donated to the National Cord Blood Bank. In most cases, the chance that you will need it for your own child is unlikely, unless there is already a known condition in the family."

For example, if there is a history of leukemia in another child, it may be worthwhile. Bonesho said in a case like that, having the baby's own blood stem cells can be the perfect answer.

"However, chances are good that if there is a sibling, they may also be a good match if a bone marrow transplant is needed," Bonesho said. "However, transplants are not the normal course of treatment in children with leukemia."

That being said, the cord blood could eventually be used for research in the future to find a cure for diseases like sickle cell anemia, Bonesho said.

Federal funding for much stem cell research is blocked mainly over the opposition to using embryonic stem cells. The cells come from blastocysts (fertilized eggs) from an in-vitro facility. The blastocysts are excess and are usually donated by people who have already been successfully treated for fertility problems.

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The promise and hazards of stem cell research

Stem cell type resists chemotherapy drug

A new study shows that adipose-derived human stem cells, which can become vital tissues such as bone, may be highly resistant to the common chemotherapy drug methotrexate (MTX). The preliminary finding from lab testing may prove significant because MTX causes bone tissue damage in many patients.

MTX is used to treat cancers including acute lymphoblastic leukemia, the most common form of childhood cancer. A major side effect of the therapy, however, is a loss of bone mineral density. Other bone building stem cells, such as bone marrow derived stem cells, have not withstood MTX doses well.

"Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs," said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. "That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldn't have these issues."

Stem cell survivors

Originally Beane was doing much more basic research. She was looking for chemicals that could help purify adipose-derived stem cells (ASCs) from mixed cell cultures to encourage their proliferation. Among other things, she she tried chemotherapy drugs, figuring that maybe the ASCs would withstand a drug that other cells could not. The idea that this could help cancer patients did not come until later.

In the study published online in the journal Experimental Cell Research, Beane exposed pure human ASC cultures, "stromal vascular fraction" (SVF) tissue samples (which include several cell types including ASCs), and cultures of human fibroblast cells, to medically relevant concentrations of chemotherapy drugs for 24 hours. Then she measured how those cell populations fared over the next 10 days. She also measured the ability of MTX-exposed ASCs, both alone and in SVF, to proliferate and turn into other tissues.

Beane worked with co-authors fellow center member Eric Darling, the Manning Assistant Professor in the Department of Molecular Pharmacology, Physiology and Biotechnology, and research assistant Vera Fonseca.

They observed that three chemotherapy drugs -- cytarabine, etoposide, and vincristine -- decimated all three groups of cells, but in contrast to the fibroblast controls, the ASCs withstood a variety of doses of MTX exceptionally well (they resisted vincristine somewhat, too). MTX had little or no effect on ASC viability, cell division, senescence, or their ability to become bone, fat, or cartilage tissue when induced to do so.

The SVF tissue samples also withstood MTX doses well. That turns out to be significant, Darling said, because that's the kind of tissue that would actually be clinically useful if an ASC-based therapy were ever developed for cancer patients. Hypothetically, fresh SVF could be harvested from the fat of a donor, as it was for the study, and injected into bone tissue, delivering ASCs to the site.

To understand why the ASCs resist MTX, the researchers conducted further tests. MTX shuts down DNA biosynthesis by binding the protein dihydrofolate reductase so that it is unavailable to assist in that essential task. The testing showed that ASCs ramped up dihydrofolate reductase levels upon exposure to the drug, meaning they produced enough to overcome a clinically relevant dose of MTX.

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Stem cell type resists chemotherapy drug

Bone marrow transplants can reverse adult sickle cell disease

This image provided by the National Institutes of Health shows red blood cells in a patient with sickle cell disease at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

This image provided by the National Institutes of Health shows red blood cells in a different sickle cell patient, after a bone marrow transplant at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results seen with a similar technique used in children.

The researchers and others say the findings show age need not be a barrier and that the technique may change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were even able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening; patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, with hopes that the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

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Bone marrow transplants can reverse adult sickle cell disease

News Review From Harvard Medical School — Transplant May Help Adults with Sickle Cell

July 2, 2014

News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

A partial transplant of bone-marrow stem cells may reverse sickle cell disease in adults, a new study finds. People with sickle cell disease have abnormally shaped red blood cells. They get stuck in blood vessels. This causes organ damage, pain and other medical problems. The new study included 30 adults with severe sickle cell disease. Each of them had a brother or sister who was a suitable match for a bone-marrow stem cell transplant. The sibling donor's cells were mixed with some of the patient's own cells. During 3.4 years of follow-up, the partial transplant reversed sickle cell disease in 26 out of 30 people, researchers said. In these patients, the bone marrow began making normal red blood cells. Fifteen people also were able to stop taking drugs to prevent rejection of the transplant. Overall, people were much less likely than before to need hospital treatment for the disease. Use of narcotic drugs for pain also was greatly reduced. The Journal of the American Medical Association published the study. HealthDay News wrote about it July 1.

By Howard LeWine, M.D.Harvard Medical School

What Is the Doctor's Reaction?

In the United States, more than 90,000 people are affected by sickle cell disease. Most of them are African-American. Worldwide, the number is much higher. About 300,000 babies are born with this genetic disease every year.

In sickle cell disease, the red blood cells made in the bone marrow are abnormal. Instead of having a normal round shape, the cells are curved and stiff. This causes the red blood cells to get stuck inside blood vessels before they reach the tissues. The result:

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News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

Special Harvard Commentary: How Stem Cells Help Treat Human Disease

Last reviewed and revised on May 20, 2013

By Anthony L. Komaroff, M.D. Brigham and Women's Hospital

Both adult and umbilical cord stem cells already are used to treat disease.

Adult stem cells:

For many years, doctors have used adult stem cells successfully to treat human disease, through bone marrow transplantation (also known as hematopoietic stem cell transplantation). Most often, this treatment is used to treat cancers of the bloodlymphomas and leukemias. When all other treatments have failed, the only hope for a cure is to wipe out all of the patients blood cellsthe cancerous ones and the healthy onesand to give a patient an entirely new blood system. The only way to do this is to transplant blood stem cellscells that can reproduce themselves indefinitely and turn into all types of specialized blood cells.

Here's how it's done. First, the doctors need to collect blood stem cells from a patient's bone marrow, and let them multiply.

Second, the patient is given a dose of chemotherapy that kills all of the cancer cells a dose that, unfortunately, also kills the cells in the patient's bone marrow.

Third, the blood stem cellsthe cells designed to give the patient a whole new blood systemare given to the patient through an intravenous catheter. Hopefully, the blood stem cells then travel through the blood to the bone marrow, where they take up residence and start to make a new blood system.

Where do the blood stem cells come from? Most of the time, they come from the patient himself. They are sucked out of the patients bone marrow through a needle, or taken from the patients blood (some blood stem cells travel in the blood). So the blood stem cells are outside the patients body, growing in a laboratory dish, when the patient is given the chemotherapy that kills all the blood cells still inside the body.

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Special Harvard Commentary: How Stem Cells Help Treat Human Disease

Research team pursues techniques to improve elusive stem cell therapy

Stem cell scientists had what first appeared to be an easy win for regenerative medicine when they discovered mesenchymal stem cells several decades ago. These cells, found in the bone marrow, can give rise to bone, fat, and muscle tissue, and have been used in hundreds of clinical trials for tissue repair. Unfortunately, the results of these trials have been underwhelming. One problem is that these stem cells don't stick around in the body long enough to benefit the patient.

But Harvard Stem Cell Institute (HSCI) scientists at Boston Children's Hospital aren't ready to give up. A research team led by Juan Melero-Martin, PhD, recently found that transplanting mesenchymal stem cells along with blood vessel-forming cells naturally found in circulation improves results. This co-transplantation keeps the mesenchymal stem cells alive longer in mice after engraftment, up to a few weeks compared to hours without co-transplantation. This improved survival gives the mesenchymal stem cells sufficient time to display their full regenerative potential, generating new bone or fat tissue in the recipient mouse body. The finding was published in the Proceedings of the National Academy of Sciences (PNAS).

"We are losing mesenchymal stem cells very rapidly when we transplant them into the body, in part, because we are not giving them what they need," said Melero-Martin, an HSCI affiliated faculty member and an assistant professor of surgery at Boston Children's Hospital, Harvard Medical School.

"In the body, these cells sit very close to the capillaries, constantly receiving signals from them, and even though this communication is broken when we isolate mesenchymal stem cells in a laboratory dish, they seem to be ok because we have learned how to feed them," he said. "But when you put the mesenchymal stem cells back into the body, there is a period of time when they will not have this proximity to capillary cells and they start to die; so including these blood vessel-forming cells from the very beginning of a transplantation made a major difference."

Melero-Martin's research has immediate translational implications, as current mesenchymal clinical trials don't follow a co-transplantation procedure. He is already collaborating with surgical colleagues at Boston Children's Hospital to see if his discovery can help improve fat and bone grafts. However, giving patients two different types of cells, as opposed to just one, would require more time and experiments to determine safety and efficacy. Melero-Martin is seeking to identify the specific signals mesenchymal stem cells receive from the blood vessel-forming cells in order to be able to mimic the signals without the cells themselves.

"Even though mesenchymal stem cells have been around for a while, I think there is still a lack of fundamental knowledge about communication between them and other cells in the body," he said. "My lab is interested in going even beyond what we found to try to understand whether these cell-cell signals are different in each tissue of the body, and to learn how to educate both blood vessel-forming and mesenchymal stem cells to co-ordinate tissue specific regenerative responses."

Other Harvard Stem Cell Institute researchers are studying mesenchymal stem cells as bioengineering tools to deliver therapeutics, which is possible because of the cell type's unique ability to not trigger an immune response. Jeffrey Karp, PhD, at Brigham and Women's Hospital has developed several methods to turn these cells into drug-delivery vehicles, so that after transplantation they can, for example, hone in on swollen tissue and secrete anti-inflammatory compounds. And Khalid Shah, PhD, at Massachusetts General Hospital has designed a gel that holds mesenchymal stem cells in place so that they can expose brain tumors to cancer-killing herpes viruses.

"A lot of these applications have no real direct link with mesenchymal stem cells' supposed progenitor cell function," Melero-Martin said. "In our study, we went back to the collective ambition to use these cells as a way to regenerate tissues and we are not in a position to say how that affects other uses that people are proposing."

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

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Research team pursues techniques to improve elusive stem cell therapy

Bone marrow transplantation shows potential for treating adults with sickle cell disease

PUBLIC RELEASE DATE:

1-Jul-2014

Contact: Krysten Carrera krysten.carrera@nih.gov 301-435-8112 The JAMA Network Journals

Use of a lower intensity bone marrow transplantation method showed promising results among 30 patients (16-65 years of age) with severe sickle cell disease, according to a study in the July 2 issue of JAMA.

Myeloablative (use of high-dose chemotherapy or radiation) allogeneic hematopoietic stem cell transplantation (HSCT; receipt of hematopoietic stem cells "bone marrow" from another individual) is curative for children with severe sickle cell disease, but associated toxicity has made the procedure prohibitive for adults. The development of nonmyeloablative conditioning regimens (use of lower doses of chemotherapy or radiation to prepare the bone marrow to receive new cells) may facilitate safer application of allogeneic HSCT to eligible adults, according to background information in the article.

Matthew M. Hsieh, M.D., of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., and colleagues explored a nonmyeloablative approach in a pilot group of 10 adults with severe sickle cell disease, using a simplified HSCT regimen (with stem cell donation from a immunologically matched sibling), that had few toxic effects, yet all patients continued taking immunosuppression medication. The researchers have since revised the protocol to include an option to stop immunosuppression after 1 year in selected patients (those with donor CD3 engraftment of greater than 50 percent and normalization of hemoglobin). In this report, the authors describe the outcomes for 20 additional patients with severe sickle cell disease, along with updated results from the first 10 patients. All 30 patients (ages 16-65 years) were enrolled in the study from July 2004 to October 2013.

As of October 25, 2013, 29 patients were alive with a median follow-up of 3.4 years, and 26 patients (87 percent) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. Hemoglobin levels improved after HSCT; at 1 year, 25 patients (83 percent) had full donor-type hemoglobin. Fifteen engrafted patients discontinued immunosuppression medication and had no graft-vs-host disease.

The average annual hospitalization rate was 3.2 the year before HSCT, 0.63 the first year after, 0.19 the second year after, and 0.11 the third year after transplant. Eleven patients were taking narcotics long-term at the time of transplant. During the week they were hospitalized and received their HSCT, the average narcotics use per week was 639 mg of intravenous morphine-equivalent dose. The dosage decreased to 140 mg 6 months after the transplant.

There were 38 serious adverse events including pain, infections, abdominal events, and toxic effects from the medication sirolimus.

"In this article, we extend our previous results and show that this HSCT procedure can be applied to older adults, even those with severe comorbid conditions " the authors write. "These data reinforce the low toxicity of this regimen, especially among patients with significant end-organ dysfunction."

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Bone marrow transplantation shows potential for treating adults with sickle cell disease

UVA Expands Cancer Treatment

UVA joins National Marrow Donor Program giving greater access to cancer treatments by Ishaan Sachdeva | Jun 25 2014 | 06/25/14 10:11pm | Updated 06/30/14 9:56pm

The Emily Couric Cancer Center of the University of Virginia Health System has expanded its access to bone marrow and hematopoietic stem cell transplant donors. Now designated as a National Marrow Donor Program (NMDP), the Health System will have access to the Be The Match Registry, the worlds largest and most diverse bone marrow registry. Implications of this change are significant for patients afflicted with blood cancers like leukemia who obtain treatment through the Health System.

Bone marrow, the soft, spongy tissue within bones like the sternum or the ilium of the pelvis, forms hematopoietic or blood-forming stem cells. These cells, unlike embryonic stem cells, differentiate only into types of blood cells- red blood cells, white blood cells or clotting platelets. Leukemia causes bone marrow to produce abnormal, leukemic white blood cells that divide uncontrollably, forming tumors that deprive cells of oxygen and reduce infection defense. One treatment method is autologous bone marrow transplant, in which patients receive stem cells from their healthy, non cancerous bone marrow.

The idea [of autologous transplants] is that you extract healthier bone marrow from the patient to have a source of stored, non-cancerous bone marrow. You can then treat the patient with higher doses of treatment than you can normally give because the most common limitation to treatment is that treatment will kill off healthy bone marrow you might have, said Thomas P. Loughran Jr., MD, the Universitys Cancer Center director.

Essentially, a patients healthy bone marrow is safeguarded outside their body while aggressive treatment is administered to kill cancerous marrow. Another form of treatment is allogeneic treatment, in which bone marrow is transplanted from a sibling or an unrelated donor.

In an allogeneic transplant, you are also transplanting in a new immune system. The new immune system comes in and recognizes the body as a foreign tissue and starts attacking that tissue. This causes a beneficial graft vs. leukemia effect where this new immune system attacks any residual leukemia, but may also cause a harmful graft versus host disease where normal tissue is also attacked, Loughran said.

The donor and recipient tissue interaction underscores the genetic component of bone marrow transplants from external donors. Despite the curative potential of a bone marrow transplant, a strong genetic match between donor and recipient is crucial to the utility of a transplant.

The ability of any donor to be successful is based on genetics. Its called HLA [human leukocyte antigen] typing. The HLA system has four genes called A, B, C and D, and it turns out that A, B and D are influential. We have half of our genes each from both parents, so we have six of these: 2 A, 2 B and 2 D. The best case is a six out of six match from a brother or sister, but the chances are only 1 in 4, said Loughran. The consequence of low genetic probabilities is a large pool of unrelated donors, like the Be The Match Registry. Through such services, patients have a greater chance of finding an unrelated donor who may provide a successful genetic match.

The coordinating center would identify the place where the donor is living and tell them they are potentially able to donate. In the past, the donor would have bone marrow directly extracted. Now it is almost always from the PBSCT [peripheral blood stem cell transplantation] procedure. The donor takes a growth factor that stimulates growth of the needed hematopoietic stem cells within their peripheral blood circulation. A catheter collects this blood and the stem cells are separated from the blood by a machine, and the blood is returned back to the donor. The collected stem cells are sent to the lab where they are purified and frozen, Loughran said.

Meanwhile, the patient in preparation for the transplant is given the highest dose of chemotherapy that can be tolerated. The donated stem cells are administered to the patient in a way similar to IV fluid.

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UVA Expands Cancer Treatment

Study finds new treatment for adult sickle cell disease

Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results from a similar technique used in children.

The researchers and others say the findings show that age need not be a barrier and that the technique could change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

Sickle cell disease is a genetic condition that damages oxygen-carrying hemoglobin in red blood cells that then form sickle shapes that can block blood flow through veins. It can cause anemia, pain and organ damage. The disease affects about 100,000 Americans and millions worldwide.

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening. Patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, hoping the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

Results from the adult study, involving patients aged 29 on average, were published Tuesday in the Journal of the American Medical Association.

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Study finds new treatment for adult sickle cell disease

Autologous stem cell treatment could be the road ahead

The treatment could edge out joint replacement procedures to a large extent.

Hyderabad, June 30:

A team of doctors from a city hospital have harvested stem cells of a person using bone marrow from the pelvis area to replace some dead tissues in the hip. By doing this, they saved the patient from undergoing a hip replacement.

The Apollo Health City team, headed by orthopaedic specialist Paripati Sharat Kumar, diagnosed a 39-year-old women suffering from Avascular Necrosis. Her condition would require undergoing a replacement of hips.

After assessing her condition, the team has decided to go for the autologous stem cell procedure (where donor and the receiver is the same person) to save both the hip joints.

The minimally invasive procedure involved taking bone marrow aspirate from the patients pelvis. Stem cells were harvested from the aspirate through a process that takes about 15 minutes. Stems cells were planted in the area of damage under fluoroscopy control following core decompression, Kumar said in a statement on Monday.

He feels that the autologous stem cell treatment could edge out joint replacement procedures to a large extent in the days to come. The scope of this procedure in orthopaedics and sports medicine is enormous. This could be extended to indications including osteoarthritis of knee, shoulder, hip, elbows, ankle and spine, he said.

(This article was published on June 30, 2014)

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Autologous stem cell treatment could be the road ahead

Her own stem cells saved her from hip replacement

Apollo Health City team did autologous stem cell procedure to save both the hip joints

Hyderabad, June 30:

A team of doctors from a city hospital have harvested stem cells of a person using bone morrow from the pelvis area to replace some dead tissues in the hip. In this process, they saved the patient from undergoing a hip replacement.

The Apollo Health City team, headed by orthopaedic specialist Paripati Sharat Kumar, diagnosed a 39-year-old woman to be suffering from Avascular Necrosis, making her writhe with pain in her two hip joints. Her condition would require undergoing a replacement of hips.

After assessing her condition, the team has decided to go for autologous stem cell procedure (where donor and the receiver is the same person) to save both the hip joints.

The minimally invasive procedure involved taking bone marrow aspirate from the patients pelvis. Stem cells were harvested from the aspirate, through a process that takes about 15 minutes. Stems cells were planted in the area of damage under fluoroscopy control following core decompression, Sharat Kumar said here in a statementon Monday.

He felt that autologous stem cell treatments could edge out joint replacement procedures to a large extent in days to come. The scope of this procedure in orthopaedics and sports medicine is enormous. This could be extended to indications include osteoarthritis of knee, shoulder, hip, elbows, ankle and spine, he said.

(This article was published on June 30, 2014)

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Her own stem cells saved her from hip replacement

Charlotte Crosby helps young boy in need of bone marrow transplant

Geordie Shore star Charlotte Crosby has become the latest person to sign up to the Anthony Nolan bone marrow register

Geordie Shore star Charlotte Crosby has spat out her support for a baby in need of a life-saving operation.

Charlotte has signed up with the Anthony Nolan Trust after reading about the plight of nine-month-old Joey Ziadi, who is suffering from a rare blood disorder that affects one in nine million people.

The tot from Northampton needs a lifesaving transplant but has not yet found a matching donor so Charlotte has enlisted her 1.89m twitter followers to join the cause.

After hearing about Joeys plight, Charlotte tweeted a selfie with her Anthony Nolan spit kit - the simple piece of equipment which allows people to leave a DNA sample and go on the bone marrow donor register.

She said: I saw the gorgeous Joey Ziadi in the news and I couldnt believe it when I heard how ill he was and that only one in nine million people have his condition I felt like crying. I knew I had to do something, but I didnt know how to help.

When I found out how simple it was to sign up to the Anthony Nolan register, I didnt have to think about it. I just thought Its so easy, why doesnt everyone do this?

Anthony Nolan saves lives by matching people willing to donate their bone marrow or blood stem cells to patients in need of a transplant.

The charity also needs more young men to sign up, as they are most likely to be chosen to donate but make up just 14% of the register. Charlotte said: I was quite shocked that young lads are so underrepresented on the register though. Come on lads, just sign up online and spit into a tube! Im doing it, and I just hope one day I have the chance to save a life.

Joey was diagnosed with an extremely rare blood disorder Diamond Blackfan Anaemia in February. His family have been campaigning to recruit more potential donors to the Anthony Nolan donor register after being told that his best hope of a cure is a bone marrow transplant from a stranger.

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Charlotte Crosby helps young boy in need of bone marrow transplant

Designer T cells fight viruses after transplants – Quincy Herald-Whig | Illinois & Missouri News, Sports

By LAURAN NEERGAARD AP Medical Writer

WASHINGTON (AP) - Bone marrow transplants save thousands of lives but patients are vulnerable to severe viral infections in the months afterward, until their new immune system kicks in. Now scientists are developing protection for that risky period - injections of cells specially designed to fend off up to five different viruses at once.

"These viruses are a huge problem, and there's a huge need for these products," said Dr. Ann Leen, who leads a team at Baylor College of Medicine and Texas Children's Hospital that found an easier way to produce these long-desired designer T cells.

Healthy people have an army of T cells that roams the body, primed to recognize and fight viruses. People with suppressed immune systems - such as those undergoing a bone marrow transplant to treat leukemia or other diseases - lack that protection. It can take anywhere from four months to more than a year for marrow stem cells from a healthy donor to take root and start producing new immune cells for the recipient. When patients get sick before then, today's antiviral medications don't always work and cause lots of side effects.

The proposed solution: Take certain virus-fighting T cells from that same bone marrow donor, and freeze them to use if the recipient gets sick. Years of experiments show it can work. But turning the idea into an easy-to-use treatment has been difficult. A dose had to be customized to each donor-recipient pair and protected against only one or two viruses. And it took as long as three months to make.

Wednesday, Leen reported a novel technique to rapidly manufacture so-called virus-specific T cells that can target up to five of the viruses that cause the most trouble for transplant patients: Epstein-Barr virus, adenovirus, cytomegalovirus, BK virus, and human herpesvirus 6.

Essentially, Leen came up with a recipe to stimulate donated T cells in the laboratory so that they better recognize those particular viruses, and then grow large quantities of the cells. It took just 10 days to create and freeze the designer T cells.

To see if they worked, Leen's team treated 11 transplant recipients. Eight had active infections, most with multiple viruses. The cell therapy proved more than 90 percent effective, nearly eliminating all the viruses from the blood of all the patients, Leen reported in the journal Science Translational Medicine.

The other three patients weren't sick but were deemed at high risk. They were given early doses of the T cells protectively and remained infection-free, Leen said.

Next, her team is beginning a bigger step - to try creating a bank of those cells from a variety of healthy donors that any patient could use, without having to custom-brew each dose.

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Designer T cells fight viruses after transplants - Quincy Herald-Whig | Illinois & Missouri News, Sports

Fat of the bone: Exercise, diabetes affect amount of fat inside bones

In your bones, there is fat.

Why? Researchers don't know, but they have theories.

How does it get there? They have theories about that, too.

Is it the same sort of fat found in muscle? Not sure.

Is this bone fat a bad thing? Yes. Researchers think it is. But sometimes, they say, it might not be so bad.

"This is a new field," said Maya Styner, MD, an assistant professor of medicine in the University of North Carolina School of Medicine. "We don't know exactly how it's produced or why it's there to begin with. There are a lot of unanswered questions."

But Styner, an endocrinologist, has used a new kind of imaging technique to answer at least two: what do diabetes drugs and exercise -- or the lack of it -- do to bone fat, and why does this matter?

Stains and scans

Our bones are not stagnant, rock-like things. They change. Marrow -- the tissue inside bones -- is full of various kinds of cells. And marrow is also full of fat. The amounts of these cells and fats can decrease or increase over time. And the production of these marrow cells and fat depend on a specific type of progenitor cell called a mesenchymal stem cell.

"These stem cells give rise to both bone and fat," Styner said. "For a long time in the bone world, it's been thought that these stem cells produce bone but then, as we age, they start to produce fat, instead."

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Fat of the bone: Exercise, diabetes affect amount of fat inside bones

Fat of the Bone

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Newswise In your bones, there is fat.

Why? Researchers dont know, but they have theories.

How does it get there? They have theories about that, too.

Is it the same sort of fat found in muscle? Not sure.

Is this bone fat a bad thing? Yes. Researchers think it is. But sometimes, they say, it might not be so bad.

This is a new field, said Maya Styner, MD, an assistant professor of medicine in the University of North Carolina School of Medicine. We dont know exactly how its produced or why its there to begin with. There are a lot of unanswered questions.

But Styner, an endocrinologist, has used a new kind of imaging technique to answer at least two: what do diabetes drugs and exercise or the lack of it do to bone fat, and why does this matter?

Stains and scans

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Fat of the Bone

Umbilical cord blood helps to save lives

SOUTH BEND, Ind.--- In the 1970's, researchers discovered that a newborn's umbilical cord blood contained special stem cells that could help fight certain diseases.

More than 30 years later doctors are still experimenting and learning more about the use of cord blood.

Amanda Canale doesn't take time with her daughter and niece for granted.

She's just happy to feel good.

"I've been in the hospital, and I've been sick my whole life," said Amanda.

Amanda was born with a rare blood disorder that required daily shots.

"Basically, I have no white blood cells. I have no immune system at all," said Amanda

At 23 she developed Leukemia and was given two weeks to live.

She desperately needed a Bone Marrow Transplant, but family members weren't matches.

Her doctor suggested an Umbilical Cord Blood Transplant.

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Umbilical cord blood helps to save lives

Lesson learned at Hutch helping dogs with lymphoma

Originally published June 18, 2014 at 4:37 PM | Page modified June 19, 2014 at 8:32 PM

BELLINGHAM A decade ago, the San Juan Island owners of Comet brought their beloved golden retriever to Drs. Edmund Sullivan and Theresa Westfall at Bellingham Veterinary to see if Comets diagnosis of lymphoma could be treated as something other than a death sentence.

The odds werent good.

At the time, lymphoma was considered incurable, with chemotherapy treatment only a temporary solution because the cancer nearly always re-emerged and resulted in death within a year.

Sullivan and Westfall, who are married, were determined to help. After talking to Dr. Rainer Storb, an expert on human lymphoma at Fred Hutchinson Cancer Research Center in Seattle, they decided to attempt a bone-marrow transplant on Comet. They spent six months visiting the center to learn how.

After removing and preserving bone-marrow stem cells in a painless procedure, the cells are stored for re-injection after radiation therapy. Through DNA analysis, the patients cells are checked for the presence of tumor cells. Sometimes, blood transfusions are needed to provide platelets and red blood cells during recovery.

Its a common procedure in humans but hadnt been tried with dogs.

It worked. Comet survived.

Since Comets recovery, more than 100 dogs have been cured with the treatment through Bellingham Veterinary, and three more veterinary hospitals around the country have been trained in the procedure. The 50 percent cure rate is considered extraordinary.

I didnt invent the procedure, Sullivan says. The knowledge was already out there and we just applied it to dogs.

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Lesson learned at Hutch helping dogs with lymphoma

MP calls for more donors in Pendle to register

MP calls for more donors in Pendle to register

11:43am Tuesday 17th June 2014 in News

THE Anthony Nolan charity is searching for more heroes in Pendle to join their bone marrow register in the fight against blood cancer.

Championed by Pendle MP Andrew Stephenson, this search is under way as the Anthony Nolan bone marrow register has been mapped across the UK by area for the first time.

In Pendle, there are more than 1,500 residents willing to donate their stem cells, or bone marrow, to save the life of a stranger.

Anthony Nolan, now in its 40th anniversary year, was the worlds first bone marrow register.

Mr Stephenson said: I am delighted that Pendle has one of the highest number of heroes on the register out of anywhere in Britain, but we could get even more.

Im hunting for more people to sign up today, so we can fight blood cancer together. It is something truly heroic to give a stranger a second chance at life. That is why Im proud of the huge number of Pendle residents already signed up and proud to champion this cause.

For details, visit www. anthonynolan.org/superhero.

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MP calls for more donors in Pendle to register

Children's Research Institute Finds Key to Identifying, Enriching Mesenchymal Stem Cells

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Newswise DALLAS June 20, 2014 The Childrens Medical Center Research Institute at UTSouthwestern (CRI) has identified a biomarker that enables researchers to accurately characterize the properties and function of mesenchymal stem cells (MSCs) in the body. MSCs are the focus of nearly 200 active clinical trials registered with the National Institutes of Health, targeting conditions such as bone fractures, cartilage injury, degenerative disc disease, and osteoarthritis.

The finding, published in the journal Cell Stem Cell on June 19, significantly advances the field of MSC biology, and if the same biomarker identified in CRIs studies with mice works in humans, the outlook for clinical trials that use MSCs will be improved by the ability to better identify and characterize the relevant cells.

There has been an increasing amount of clinical interest in MSCs, but advances have been slow because researchers to date have been unable to identify MSCs and study their normal physiological function in the body, said Dr. Sean Morrison, Director of the Childrens Research Institute, Professor of Pediatrics at UTSouthwestern Medical Center, and a Howard Hughes Medical Institute Investigator. We found that a protein known as leptin receptor can serve as a biomarker to accurately identify MSCs in adult bone marrow in vivo, and that those MSCs are the primary source of new bone formation and bone repair after injury.

In the course of their investigation, the CRI researchers found that leptin receptor-positive MSCs are also the main source of factors that promote the maintenance of blood-forming stem cells in the bone marrow.

Unfortunately, many clinical trials that are testing potential therapies using MSCs have been hampered by the use of poorly characterized and impure collections of cultured cells, said Dr. Morrison, senior author of the study and holder of the Mary McDermott Cook Chair in Pediatric Genetics at UTSouthwestern. If this finding is duplicated in our studies with human MSCs, then it will improve the characterization of MSCs that are used clinically and could increase the probability of success for well-designed clinical trials using MSCs.

Dr. Bo Zhou, a postdoctoral research fellow in Dr. Morrisons laboratory, was first author of the paper. Other CRI researchers involved in the study were Drs. Rui Yue and Malea Murphy, both postdoctoral research fellows. The research was supported by the National Heart, Lung, and Blood Institute, the Cancer Prevention and Research Institute of Texas, and donors to the Childrens Medical Center Foundation.

About CRI

Childrens Medical Center Research Institute at UTSouthwestern (CRI) is a joint venture established in2011 to build upon the comprehensive clinical expertise of Childrens Medical Center of Dallas and the internationally recognized scientific excellence of UTSouthwestern Medical Center. CRIs mission is to perform transformative biomedical research to better understand the biological basis of disease, seeking breakthroughs that can change scientific fields and yield new strategies for treating disease. Located in Dallas, Texas, CRI is creating interdisciplinary groups of exceptional scientists and physicians to pursue research at the interface of regenerative medicine, cancer biology and metabolism, fields that hold uncommon potential for advancing science and medicine. More information about CRI is available on its website: cri.utsw.edu

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Children's Research Institute Finds Key to Identifying, Enriching Mesenchymal Stem Cells

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