Canadian Blood Services has renewed its partnership with DDB Canada and OMD Canada; signing a new, three-year contract for strategic advertising and media management services. Both DDB and OMD will continue to help recruit and retain the next generation of blood donors in Canada, in addition to helping expand and diversify the OneMatch Stem Cell and Marrow Network.

The selection of DDB Canada and OMD Canada followed a rigorous RFP process which narrowed the field from 16 responses to a short list of 6 potential Canadian agencies.

“We are excited to continue building on the collaborative and creative strategies developed with DDB Canada and OMD Canada over the past four years,” says Ian Mumford, Canadian Blood Services’ Chief Operating Officer. “As committed strategic partners, they have demonstrated their commitment to our cause and are prepared to invest heavily in the creative process to develop ground-breaking ideas for donor recruitment, enhance our strategic platform and support a long-term recruitment strategy. Over the next three years, our partnership with DDB Canada and OMD Canada will help us inspire more Canadians from all walks of life to become regular blood donors and stem cell registrants.”

DDB Canada will continue as the advertising agency partner responsible for strategic planning and advertising. OMD Canada will continue as the agency responsible for strategic media planning and placement of Canadian Blood Services advertising.

“The simple fact is, we as an agency couldn’t imagine not working with Canadian Blood Services,” says David Leonard, DDB Canada’s National President and Chief Operating Officer. “With a cause so central to the vitality of all Canadians, our work together is unfortunately never done. We’re excited to extend our relationship and commitment to such a worthy cause, and look forward to the task of helping change how Canadians think and feel about the act of giving blood – of giving life.”

“We are thrilled that our close partnership with Canadian Blood Services will continue,” says Lorraine Hughes, President, OMD Canada. “Our commitment and dedication to the cause at OMD is unwavering. We will continue to get the message to as many Canadians as possible that the gift of blood can and will change someone’s life. What a fantastic opportunity to be involved in a cause that is so important to all of us.”

DDB Canada and OMD Canada first became agency of record partners with Canadian Blood Services on April 1, 2006. Canadian Blood Services, DDB Canada and OMD Canada will officially renew the three-year relationship on April 1, 2010.

About DDB Canada

Named Strategy’s 2009 Agency of the Year and Top Creative Agency, DDB Canada is the most creatively acclaimed, internationally recognized marketing communications agency in Canada. Known for advertising that generates significant results for clients, DDB Canada is a “total communications company” whose fundamental belief is that creativity is the most powerful force in business. DDB Canada has offices in Vancouver, Edmonton, Toronto and Montreal. The agency’s integrated groups include: DDB Kid Think (youth marketing), DDB Public Relations, Tribal DDB (online and interactive), Karacters Design Group, Rapp Collins (direct) and Radar DDB (social media marketing).

About OMD Canada

OMD is Canada’s single largest media management company. Adweek Magazine recently selected OMD as its 2009 Global Media Agency of the Year. OMD also ranked #1 in the 2005 Gunn Report which recognizes achievement in media creativity. OMD was established in 1999 and has offices in Toronto, Montreal and Vancouver. OMD Canada is a member of OMD Worldwide and is affiliated with Omnicom’s three agency networks: BBDO, DDB and TBWA.

Canadian Blood Services

UK researchers have discovered a way of improving the effectiveness of bone marrow transplantation, a key treatment for many patients with blood cancer, by providing an extra ‘boost’ to the immune system.

Each year in the UK, over 1000 patients receive blood or bone marrow transplants from a healthy donor as treatment for leukaemia or lymphoma. This therapy not only provides the patient with a new bone marrow but also a new immune system. This means that immune cells from the donor can attack the blood cancer, known as the ‘graft-versus-leukaemia’ effect. Killing residual blood cancer cells is a critical part of the transplant process and is almost certainly necessary to achieve a cure.

The researchers from the University College London, together with collaborators at Harvard and Columbia Universities in the United States, examined why blood cancers come back in some patients who receive a transplant. In a study funded by the charity Leukaemia & Lymphoma Research, and published online in the Journal Of Clinical Investigation, the scientists showed that cancer-targeting immune cells can become ‘worn out’ and stop working. This means that the graft-versus-leukaemia effect may be lost. Importantly, a new treatment can revive the ‘tired’ immune cells and get them to start working again.

By using clinically relevant mouse models of bone marrow transplantation, the researchers found that normal tissues outside the bone marrow were responsible for causing ‘exhaustion’ of the immune cells. This occurred because the normal cells have a molecule on their surface that eventually switches off the immune cells. They went on to show that treatment with an antibody could block this molecule and re-invigorate the immune system. Importantly, this could be done safely without any harmful side effects.

Dr. Ronjon Chakraverty, a bone marrow transplant physician at University College London who led the research team, said: ‘We have known for some time about the existence of the graft-versus-leukaemia response, but we didn’t understand why sometimes it doesn’t last. Our research helps to explain this failure and offers the potential of a new strategy to treat or prevent relapse of blood cancer in patients following bone marrow transplantation.’

Professor David Linch of the Cancer Institute at University College London, said: ‘These are exciting results, not only explaining why treatment may fail in some patients, but also paving the way towards improved therapy.’

Dr. David Grant, Scientific Director at Leukaemia & Lymphoma Research, said: ‘The more we understand about why bone marrow transplants can cure some patients but not others, the more we can use this form of treatment in the most effective way possible. This is a key discovery which will prevent many patients relapsing in the future.’


Leukaemia & Lymphoma Research

New findings by McMaster University researchers contradict earlier reports that people with a certain genetic make-up don’t benefit from the blood-thinner clopidogrel, also known as Plavix.

After researchers from the United States, France and Germany reported clopidogrel is less effective in some patients, the Food and Drug Administration (FDA) in the United States issued a black box warning to physicians on the drug’s package insert.

“(Our findings) add a further layer of complexity to the FDA ‘black box’ warning and show that reported genetic variants have no effect in certain patient populations,” said Dr. Guillaume Paré, lead researcher and assistant professor of pathology and molecular medicine at the Michael G. DeGroote School of Medicine.

Clopidogrel is the world’s second best-selling prescription drug with global sales of more than $6 billion annually. It is used in 110 countries by millions of people to reduce the risk of heart attack and stroke.

Following the FDA’s warning, clopidogrel became the focus of on-going debates within cardiology circles. Some American cardiologists initially called the FDA’s actions irresponsible. Others complained they were left without any appropriate direction on how to manage their patients.

About 20 per cent of the population carry the loss-of-function version of the gene involved in the clopidogrel controversy.

To assess the influence genetics might have on patients prescribed clopidogrel, Paré and colleagues from McMaster University conducted a genetic sub-study of 6,000 participants from two major clinical trials (CURE and ACTIVE). The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events) trial of 12,562 patients with acute coronary syndrome in 28 countries found clopidogrel significantly reduces the risk of heart attack stroke and dying. The ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for the Prevention of Vascular Events) trial of 7,554 patients with atrial fibrillation in 30 countries found clopidogrel added to Aspirin significantly reduced the risk of cardiovascular events, and particularly stroke. Both trials were supported by Sanofi-Aventis and Bristol-Myers Squibb.

“We found the previously reported genetic variants had no effect at all (for patients) in either the CURE or ACTIVE trials,” said Paré. He presented these findings at the European Cardiovascular Society Congress meeting in Stockholm, Sweden, on August 29. The study was also simultaneously published online in the New England Journal of Medicine.

Paré said the positive results from McMaster’s genetic sub-study come from studying different patient populations. “Also, our study design was a bit stronger from an epidemiology point of view.”

Beyond clopidogrel, he said there is a broader message of the need for cautiousness as genetics becomes more and more integrated into patient care.

Laura Thompson
McMaster University

View drug information on Plavix.

Pregnancy and surgery patients with a serious blood disorder that causes excessive clotting have responded well to treatment with a man-made anti-clotting protein. Results from a study by researchers at Yale School of Medicine and other institutions were presented December 6 at the Annual Meeting of the American Society of Hematology (ASH) in San Francisco.

The phase III, multi-center clinical trial focused on patients with the blood disorder known as hereditary antithrombin deficiency. Those who received the protein recombinant human antithrombin reported no excessive clotting during treatment or seven days after treatment.

“This is a remarkable technologic feat,” said study investigator Michael Paidas, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, and director of the Women and Children’s Center for Blood Disorders at Yale. “We’ve shown that this genetically engineered protein can prevent complications linked to antithrombin deficiency. Ours is the first team in the United States to use the protein in a clinical trial with pregnant patients.”

Antithrombin occurs naturally in the body and acts as a blood thinner that signals when blood is clotting too much. Patients with antithrombin deficiency do not naturally produce antithrombin. Low antithrombin levels can result in excessive clotting, or venous thromboembolic events (VTEs), which can complicate childbirth and surgery. Those with the condition who undergo childbirth and/or surgical procedures are at high risk for pulmonary embolism-a major cause of maternal death.

The genetic deficiency affects approximately one in 2,000 to one in 5,000 people, and half of all people diagnosed suffer a thrombosis before age 25. The deficiency can also be acquired through ailments such as liver disease, malnutrition or severe burns, which can lead to impaired production of antithrombin.

Yale was one of only two U.S. sites to participate in the study, which included 18 patients-12 pregnant and six surgical. Participants with a history or risk of VTE were given an initial dose of recombinant human antithrombin, followed by maintenance doses based on antithrombin levels. The study also showed that new dosing methods could be tailored to individual patients, which helped pregnant patients to achieve and maintain ideal antithrombin levels.

If approved by the FDA, recombinant human antithrombin will be marketed under the brand name ATryn®; the compound was developed by GTC Biotherapeutics and licensed to Ovation Pharmaceuticals, Inc. in the U.S.

Michael Paidas, M.D.

Yale University

View drug information on Atryn.

A novel strategy to hopefully beat into oblivion one of the most aggressive forms of acute myelogenous leukemia combines the strengths of some of the newest leukemia agents, researchers say.

“These are not traditional chemotherapy regimens. These are targeted therapies that our earlier laboratory studies have shown have a synergistic effect,” says Dr. Kapil N. Bhalla, director of the Medical College of Georgia Cancer Center.

The strategy takes on the mutated protein receptor that enables the deadly proliferation of leukemic cells by degrading it with histone deacetylase and heat shock protein 90 inhibitors. It uses protein kinase inhibitors to reduce the function of any remaining protein and kills off leukemic cells with a natural cell death mechanism called TRAIL.

Dr. Bhalla recently received a five-year, $1.3 million grant from the National Cancer Institute that will enable his research team to do more preclinical testing of the strategy in human leukemic cells and an AML animal model.

About six years ago, researchers found the mutation in the FLT-3 gene that results in the mutated protein receptor on the cell surface. This receptor usually responds to a growth factor that gives rise to normal bone marrow cell proliferation. “But in this case, this mutated protein receptor is constantly triggered, is constantly on and it drives proliferation, promotes survival and shuts down differentiation,” Dr. Bhalla says.

Within weeks, leukemic cells take over the bone marrow, then spread throughout the body. “Patients typically develop abnormalities of white blood cell count and platelet count, anemia or weakness and present with either an infection because they don’t have enough white blood cells or bleeding,” he says.

“We don’t know what causes these mutations, but if you have FLT-3 mutation — about 30 percent of AML patients do — then the leukemia is generally more aggressive,” says Dr. Bhalla. For whatever reason, this aggressive leukemia occurs most commonly in the elderly which means, with the aging population, it’s likely to become even more common.

“If you just target FLT-3 with an inhibitor of its activity, that would not be enough,” says Dr. Bhalla. “If you combine it with something that also depletes its levels, that would be better. But if you deplete its levels, inhibit its activity and combine it with another leukemia cell death-inducing agent, it would be even better,” says Dr. Bhalla, who believes the laboratory work will evolve into a strategy that can be used effectively in the clinics, maybe even before the laboratory work is done.

A big plus is that several drugs that do each of these things already are being studied in patients. However, combined effects of these drugs have not been fully studied against leukemia cells, and the drugs just haven’t been used together in patients with leukemia.

For example, one of the histone deacetylase inhibitors Dr. Bhalla will study in the lab, LBH589, developed by Novartis Corp., he’s also studying in an early clinical trial for patients with leukemia and lymphoma for whom standard therapies have failed. Several FLT-3 kinase inhibitors are under study for a variety of cancers and MCG will soon join one of those studies for leukemia. Apo2L/TRAIL, developed by Genetech, is under study in a variety of solid tumors and leukemia. TRAIL activates on leukemic cells the same death-inducing stimulus immune cells use to kill cancer cells. “It’s a normal mechanism of killing offending cells,” says Dr. Bhalla.

“We have designed combinations of agents that we will be studying in mouse models and against patient-derived leukemia cells. This grant doesn’t fund a clinical trial, but it allows us to take patient samples and study them in vitro to further define why this gene confers poor survival and what combinations can work against it,” says Dr. Bhalla. He notes that since the drugs are new and have not previously been used together, issues such as unforeseen toxicity will need to be explored.

“We are studying the combination and how it kills, so when the combination goes into the patient, we will be able to get samples from patients, pre- and post-treatment, to see whether what we are observing in the lab works and, if there are patients who still don’t respond, why don’t they”” says Dr. Bhalla.

Histone deacetylase and heat shock protein 90 inhibitors take direct hits at the mutant protein by targeting HSP 90, a molecular chaperone, which, in this case, improperly folds the protein, leaving it active and producing leukemic cells rather than healthy bone marrow cells as needed. Dr. Bhalla’s lab was the first to show the mutant protein kinase is particularly susceptible to depletion by targeting it with HSP 90 or histone deacetylase inhibitors. He also uncovered the synergy of kinase inhibitors.

“We are targeting HSP 90, which folds and keeps this abnormal protein in its active form,” he says. “By using this agent that targets HSP 90, you also take away many other mechanisms that drive cell proliferation and survival. Once you lower the threshold for cell death by depleting this protein, you use additional strategies to kill leukemic cells. It makes it more effective.”

Source: Toni Baker

Medical College of Georgia

Being male increases your risk of diseases caused by the inappropriate formation of a blood clot (a process known as thrombosis), such as heart attack and stroke, but the reasons for this are not completely understood. However, Ethan Weiss and colleagues at the University of California, San Francisco, have used a mouse model of thrombosis to shed new light on this matter.

Thrombosis-related proteins are made in the liver, where expression of the genes containing the information needed for their generation is regulated by growth hormone (GH), which is secreted in a sex-specific manner – males secrete GH in a pulsatile fashion, whereas females secrete GH continuously. In this study, GH-deficient mice were protected from thrombosis in the model of disease. When female GH-deficient mice were given pulsatile GH (to mimic the manner in which GH is secreted in males) their ability to form blood clots resembled male mice. Conversely, when male GH-deficient mice were given continuous GH (to mimic the manner in which GH is secreted in females) their ability to form blood clots resembled female mice. The authors therefore conclude that sex-specific patterns of GH release mediate the gender-associated differences observed in susceptibility to diseases caused by inappropriate thrombosis, information that they hope will be of help in the development of sex-specific treatments for thrombosis.

TITLE: Sex differences in thrombosis in mice are mediated by sex-specific growth hormone secretion patterns


Ethan J. Weiss

University of California, San Francisco, San Francisco, California, USA

View the PDF of this article at: https://the-jci/article.php?id=34957

Source: Karen Honey

Journal of Clinical Investigation

The American Society of Hematology (ASH) will host its annual
high school student symposium at the Georgia World Congress Center on Friday, December 7, 2007,
beginning at 8:00 a.m. EST. The symposium, which encourages an interest in hematology, the
biological sciences, and medical research, is held in conjunction with the Society’s 49th Annual
Meeting. This year, students will have the opportunity to explore research on sickle cell disease, an
inherited blood disorder, which distorts the shape of red blood cells, causing severe pain.

“The symposium is always a great opportunity to get students interested in hematology and
biomedical science in general,” said Scott D. Gitlin, MD, Chair of ASH’s Committee on Training
Programs, which helped organize the event. “Focusing on a well-known disorder like sickle cell
disease is an excellent way to introduce students to this exciting specialty.”

Students from five local high schools, including Carver School of Health Science and
Research, Mays High School, South Atlanta High School of Health and Medical Science, Therrell
High School of Engineering, Math, and Sciences, and Therrell High School of Health Science and
Research, will participate in a series of activities related to sickle cell disease during the half-day
symposium. Each student will receive a worksheet to gather data related to the presentations.
Teachers will later use the worksheet to facilitate classroom discussions.

After a kick-off breakfast, Peter Lane, MD, from Emory University, will give a presentation
focusing on the diagnosis and clinical manifestations of sickle cell disease as part of the symposium.

Later in the morning, Michael Bender, MD, of the Fred Hutchinson Cancer Research Center, will give a lecture on treatment options for sickle cell disease. Students will also have an opportunity to
hear real-life experiences from young people living with sickle cell disease.

In addition, ASH will sponsor a poster contest for symposium participants. Students, in
teams, can conduct research on sickle cell disease and present their findings in a poster and oral
presentation. ASH symposium speakers and volunteers will judge the posters, awarding the top three
groups with cash prizes of $1,500, $1,000, and $750. The prize money will then go to the winning
teams’ science departments.

The American Society of Hematology is the world’s largest professional
society concerned with the causes and treatment of blood disorders. Its mission is to further the
understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and
the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education,
training, and advocacy in hematology.

American Society of Hematology

A study published early online and in an upcoming edition of The
Lancet found that the stroke drug alteplase is safe and
effective even if administered 1 to 1.5 hours after the conventional
3-hour treatment window. Prof Nils Wahlgren (Karolinska University
Hospital, Stockholm, Sweden) and colleagues also remind that the drug
can still be safely administered within three hours of stroke.

Acute ischemic stroke is a condition characterized by a serious lack of
blood supply to the brain. It is commonly treated with a drug called
alteplase, which dissolves the thrombi (blood clot) that caused the
stroke. Usually alteplase is administered within three hours after
stroke, but Prof Wahlgren and colleagues, in the Safe Implementation of
Treatments in Stroke – International Stroke Thrombolysis Registry
(SITS-ISTR) study, tested the outcomes of patients who received
intravenous alteplase 3 to 4.5 hours after stroke. Of the total sample,
664 patients received the drug 3 to 4.5 hours post-stroke and 11,865
received it within three hours.

The group that received later treatment received alteplase about 55
minutes, on average, later than the group that received earlier
treatment – at 195 vs 140 min. In addition, the later group was about
three years younger and had slightly lower stroke severity than the
within 3 hour group. The results of the study revealed that outcome
measures were similar between the two groups. For example, the
mortality rate for the 3 to 4.5 hour group was 12.7% compared to 12.2%
for the within 3 hours group. The brain hemorrhage rates were 2.2% and
1.6% and the proportions of patients retaining independence were 58.0%
and 56.3%, respectively.

“Our results show that the rates of symptomatic intracerebral
haemorrhage, mortality, and independence at 3 months follow-up in
routine clinical practice are similar between patients for whom
treatment was started between 3 and 4.5 h and for those treated within
3 h after ischaemic stroke onset,” write the authors. “Our findings
lend support to those of the meta-analysis suggesting a potentially
longer timeframe for intravenous [use of alteplase] of 4.5 h.”

Dr Georgios Tsivgoulis and Dr Andrei Alexandrov (Comprehensive Stroke
Center, University of Alabama at Birmingham Hospital, Birmingham,
Alabama USA) write in an accompanying editorial that: “Extension of the
timeframe of systemic thrombolysis seems to be a safe option for
patients with acute stroke…We are looking forward to moving away from
rigid timeframes to treatment based on imaging that can assess brain
pathophysiology and tissue viability.”

Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke
(SITS-ISTR): an observational study
Nils Wahlgren, Niaz Ahmed, Antoni Dávalos, Werner Hacke,
Mónica Millán, Keith Muir, Risto O Roine, Danilo Toni, Kennedy R Lees,
for the SITS investigators
The Lancet (2008).
Here to View Abstract

: Peter M Crosta

Transfusion science, a discipline of biomedicine concerned with preventing the transmission of diseases associated with blood transfusion and tissue transplantation, has made significant progress in recent years. The second edition of an informative book in this field, Transfusion Science, was recently released by Scion Publishing (scionpublishing).

The first edition of Transfusion Science appeared in 1999. At that time, “[t]he potential risk of prion-related disease transmission was just beginning to be realized,” write the authors, Joyce Overfield, Maureen Dawson, and David Hamer, in the Preface to the second edition. Prions are misfolded proteins that have been implicated in a number of transmissible diseases such as “mad cow” disease. “[This risk] has now become recognized as highly significant, along with many other serious hazards of transfusion.”

The second edition of Transfusion Science has been extensively updated to cover the latest clinical and scientific applications now possible as a result of advances in molecular biology, including various analytical methods and immunotechniques. The book includes significant background information on the science and practice of immunohematology, including an overview of the immune system, antibodies and antigens, the genetic basis of blood types, and immune- and hematology-related disorders. Sections have been extended to include leukodepletion, pathogen reduction, and hemolytic anemia. Current practice in blood group serology, including the collection and processing of samples, is reviewed. Throughout the text, the latest nomenclature for blood group genes has been adopted.

The book is geared towards students studying courses on transfusion and transplantation, but it will also serve as a useful resource for healthcare professionals involved in transfusion services who are looking to understand recent progress and changes that may impact the safety of these services. To aid student understanding, the new edition has a revised design and layout. Concepts are illustrated with more case studies and color photographs, and a revised series of self-assessment questions and learning outcomes is provided.

In the March, 2008 issue of the British Journal of Biomedical Science, Paul Watson reviewed the new edition of Transfusion Science. “Hurrah!” he wrote. “At last, a new book in transfusion science that describes current laboratory procedures and protocols . . . [Focusing] predominantly on the undergraduate and trainee/specialist practitioner level, it successfully fills the gap in study material between the elementary and the higher echelons of transfusion science, delivering a solid basis of the principles and applied knowledge that will ensure this is included on many university reading lists and the shelves of blood banks.”

About the book: Transfusion Science, 2nd edition (©2007, Scion Publishing Ltd.) is 300 pp. in length and is available in paperback (ISBN 9781904842408). It was Joyce Overfield, Maureen Dawson (both Manchester Metropolitan University) and David Hamer (Royal Bolton Hospital). For details about the book, see scionpublishing/9781904842408.

About Scion Publishing Ltd.: Scion Publishing Ltd. is a publisher of innovative textbooks, methods books, and reference titles in the life and medical sciences. Their titles range from undergraduate textbooks and revision guides through to research-based monographs. Visit their website at scionpublishing/ to access their line of life science publications.

About Cold Spring Harbor Laboratory Press: CSHL Press, an internationally renowned publisher of books, journals, and electronic media on Long Island, New York, is pleased to market and distribute books for Scion Publishing in the Americas. Since 1933, CSHL Press has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit cshlpress/

Source: Jane Carter

Cold Spring Harbor Laboratory

Though we think of them as solid and permanent, our bones are actually constantly being rebuilt throughout our lives. A team of scientists at the Weizmann Institute of Science has now revealed how cells that work at remodeling the bones play a direct part in the ongoing renewal of another system – the blood. Their findings, which may lead to future improvements in bone marrow transplantation and a better understanding of diseases involving bone or blood renewal, were published in the June issue of Nature Medicine.

Bones are really two systems in one. The cavities inside bones are filled with spongy bone marrow, in which stem cells divide and their daughter cells differentiate into all kinds of blood cells, including large numbers of immune cells for the body’s defense. The hematopoietic (literally, blood-creating) stem cells, which can give rise to any kind of blood cell, reside in special ‘stem cell niches’ nestled in the bones’ inner walls. Inside these sheltered nurseries, the stem cells remain undifferentiated; with the help of other nearby cells, they hang on to their juvenile qualities. Only when they leave the niches do they morph into specialized blood cells, possibly becoming immune cells for fighting infection or cells for blood clotting and healing after injury. They can even respond to calls for help from organs such as the liver, migrating through the bloodstream to assist in repairing damage.

The inner walls of the bones are also sites of intensive reconstruction. While one type of cell, the osteoblast, is busy building bone, its partner, the osteoclast, breaks it down and reassimilates the material. Osteoclasts are formed when several cells (which themselves originate from hematopoietic stem cells) fuse together at a signal from the osteoblasts, and the two work together in a sort of ‘urban renewal’ scheme to keep the bones healthy and strong.

The Weizmann Institute team headed by Prof. Tsvee Lapidot of the Immunology
Department, which included Dr. Orit Kollet and colleagues, found that the bone-dismantling osteoclasts are instrumental in releasing hematopoietic stem cells into the bloodstream. As they wear away the bone, they allow the stem cells out of the niches and into the bloodstream. Although some hematopoietic stem cells can always be found circulating in the blood, when there is bleeding or inflammation in the body, more stem cells are needed to deal with the situation and restore balance. The team’s study showed that the bone marrow response to the body’s call for help involves stepping up production of osteoclasts, putting machinery that normally operates at a leisurely pace into high gear. The osteoclasts not only clear away bone, they also break up ‘nurturing’ substances in the niche that attract and hold the stem cells to that spot, thus allowing more stem cells into the bloodstream.

The team carried out their research on mice, including some developed in the lab of Prof. Ari Elson of the Molecular Genetics Department, in which the osteoclasts carried a mutation that rendered them only partially functional in the young females. They found abnormally low stem cell levels in the blood of these mice even when they tried to encourage their mobilization, giving them solid evidence of the connection. In normal mice, using a chemical compound that stimulates osteoclast formation, they were able to boost osteoclast levels and thus manage the release of stem cells into the blood in a variety of stress situations. This finding may have implications for bone marrow transplant techniques: The drugs given today to donors to increase the supply of stem cells in their bloodstream before they are harvested for transplantation cause the release of many other mature cells as well. Injecting the osteoclast-promoting substance into the mice, on the other hand, resulted in an increase mainly in stem cell release. These findings add a new dimension to our understanding of the processes of renewal and breakdown in the body, and the relationship between blood-forming stem cells, bone, and the immune system. In some forms of osteoporosis, autoimmune arthritis, and cancer that has metastasized to the bone, for instance, the osteoclasts demolish bone faster than it is built up. This study suggests the effects of such an imbalance may reach well beyond the bone.

Prof. Tsvee Lapidot’s research is supported by the M.D. Moross Institute for Cancer Research; the Levine Institute of Applied Science; the Belle S. and Irving E. Meller Center for the Biology of Aging; the Gabrielle Rich Center for Transplantation Biology Research; the Crown Endowment Fund for Immunological Research; the Loreen Arbus Foundation; the Concern Foundation; the Charles and David Wolfson Charitable Trust; and Silvia Schnur, Scarsdale, NY.

Prof. Lapidot is the incumbent of the Edith Arnoff Stein Professorial Chair in Stem Cell Research.

Contact: Jennifer Manning
American Committee for the Weizmann Institute of Science

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