Nearly 20 million Americans suffer from sleep apnea, a serious health condition that has been linked to increased risks for obesity and weight gain, heart attack, stroke, high blood pressure, asthma and depression. Sleep apnea has also been cited by experts as the number one cause of car accidents. Ninety-five percent of sleep apnea cases go undiagnosed, putting the health of millions of Americans at risk.

How can people determine if they suffer from sleep apnea?

- Do they have a high chance of dozing off when sitting in traffic in their car?
- What about when sitting reading, or watching TV?
- Or when they are talking with someone, or sitting inactive in a public place?

If someone answers yes to more than one of these questions, he or she could be suffering from sleep apnea. The Aviisha Medical Wellness Institute has launched a new website, aviisha, that will help them find out. Visitors can take a complete sleep apnea quiz, learn more about sleep apnea and its possible health affects, and find information on how to treat sleep apnea.

Key to the Aviisha approach is The Home Sleep Test, which enables users to determine if they suffer from sleep apnea without ever leaving home. The sleep test is easy to use, and collects data on the user’s sleeping patterns overnight. The next day, Aviisha experts evaluate the sleep test results and determine whether the patient is suffering from sleep apnea. Aviisha then provides a recommended sleep apnea treatment report, with follow-up medical treatment available through the Aviisha Medical Wellness Institute or a patient’s own physician.

The home sleep test is the only one of its kind available directly to consumers, and costs a fraction of what a sleep test conducted in a sleep lab or doctor’s office would cost. It can be ordered directly from the aviisha website at aviisha/sleep-well/home-sleep-test.

According to the National Institutes of Health, sleep apnea is a disorder in which someone has one or more pauses in breathing or shallow breaths while you sleep. These pauses can last from a few seconds to minutes, and can occur as many as 30 times or more an hour. It is usually a chronic condition that disrupts sleep three or more nights each week resulting in poor sleep quality that leads to fatigue during the day. Because most sleep apnea symptoms are somewhat generic, many people attribute their sleepiness, fatigue, stress and inability to focus to reasons other than sleep apnea.

“We are just beginning to understand how crucial sleep is to overall health,” says Dr. Avi Ishaaya, Medical Director. “If you are frequently tired, your fatigue could mean that you are at greater risk for a number of life-threatening conditions, including cardiovascular disease and high blood pressure. Sleep apnea has been directly linked to obesity and weight gain, and many experts believe it is the number one factor for car accidents. So you are not just tired if you have sleep apnea-your overall health is at serious risk. So if someone suspects they have sleep apnea, it is critical to take a sleep test to find out.”

Dr. Avi is medical director of the two Aviisha Medical Wellness Institutes-in Los Angeles and Thousand Oaks, California-where he has helped thousands of patients improve their overall health. A pioneer in sleep therapy, he is Board-certified in Pulmonary Medicine, Sleep Medicine, Internal Medicine, and Geriatrics, and is an assistant clinical professor of medicine at the UCLA School of Medicine.

Source
Each Aviisha Medical Wellness Institute

“Patient Care in Vascular and Interventional Radiology” – an essential resource and the first offering from Society of Interventional Radiology Press, the society’s publishing arm – is now available. Also available is the companion “Patient Care in Vascular and Interventional Radiology Study Guide.”

top experts in their areas of specialty, this resource is ideal for physicians in their fellowship or in training, for certification or recertification or for those who want to brush up on crucial areas of patient care. The newly updated 448-page edition of SIR’s popular syllabus covers major aspects such as vascular, neurologic, hepatobiliary, cardiac, pulmonary and genitourinary evaluation; management of hypertension, renal insufficiency, hematologic disorders, antiobiotics, analgesia and sedation, cardiopulmonary emergencies, vascular complications, liver and renal failure, postprocedural pain and nutrition; and postprocedural wound management. The spiral-bound book includes detailed tables and charts for handy reference, figures for illustration and bibliographies for further reading. Its compact size and spiral binding make it easy to carry for on-the-go learning. Book editors are Peter N. Waybill, M.D., FSIR, professor of radiology, medicine and surgery and chief of cardiovascular and interventional radiology at Pennsylvania State College of Medicine and Penn State Hershey Medical Center in Hershey, Pa., and Daniel B. Brown, M.D., professor of radiology and chief of interventional radiology and interventional oncology at Thomas Jefferson University Hospital in Philadelphia, Pa.

Also available is the first-ever “Study Guide” published by SIR Press; it is designed to complement “Patient Care in Vascular and Interventional Radiology,” presenting both questions for each of the 28 chapters covered in the syllabus and detailed answers with explanations.

Reading “Patient Care in Vascular and Interventional Radiology” constitutes a planned activity of continuing medical education with an estimated completion time of 21 hours. To receive CME credit for this activity, physicians must read the chapters in this book and take the corresponding chapter examination. The chapter exams will be available online in mid-March on the SIR Web site; all buyers will be notified as soon as the chapter exams are available. Each chapter is approved for .75 AMA PRA Category 1 Credits. Physicians do not have to complete all of the chapters to claim a CME certificate for this educational activity.

Source:
Maryann Verrillo
Society of Interventional Radiology

Siemens plc and The Stroke Association launched the third annual Stroke for Stroke campaign, in a bid to raise awareness of stroke and to highlight the benefits of a healthy diet and regular exercise in its prevention.

The campaign will run between 25 and 31 January 2010 and will challenge members of the public to row 10km (or more) during the week, helping to raise vital funds.

The campaign, a joint initiative by The Stroke Association and Siemens, the High Performance Partner of GB Rowing, is now in its third year and has raised over ВЈ70,000 to date by encouraging members of the public to complete a sponsored 10km row.

In addition to raising funds, the campaign aims to highlight that anybody, irrespective of age, can suffer from a stroke and that a healthy lifestyle, including a healthy diet and regular exercise such as rowing, can help to significantly reduce the risks.

The timing of the event at the end of January means that anyone looking to get back in shape after the festive season will still have time to warm up and shift those Christmas pounds before taking on the 10km rowing challenge.

Not having access to a rowing machine is no excuse, as the Stroke for Stroke campaign has teamed up with Nuffield Health to offer a free five day pass to their nationwide network of Fitness & Wellbeing Centres for everyone taking part in Stroke for Stroke Week.

The campaign is open to everyone across the UK by visiting strokeforstroke or calling 020 7566 1503.

Even those who can’t take part directly can still do their bit by visiting strokeforstroke and sponsoring their colleagues, friends and family or the GB Rowing squad, as they put the kilometres from their punishing training regime towards the campaign.

Olympic gold medalist, Zac Purchase, is backing the campaign, “Regular exercise is a key factor in staying healthy and reducing the risk of stroke, and rowing is an ideal, all-round, low-impact workout. It’s great to be involved in the Stroke for Stroke campaign and we hope to help raise plenty of money and awareness.”

Rachel Christie, Miss England and a talented heptathlete, is an ambassador for the campaign, comments: “A healthy diet and exercising regularly are essential for everybody. 150,000 people in the UK have a stroke every year so getting out there and taking part in Stroke for Stroke week in January will not only raise vital funds for The Stroke Association but also help improve your fitness and help lower your risk of stroke. My own family know first hand the devastating impact that a stroke can have. I am really passionate about this campaign and grateful to Siemens plc in their support of Stroke for Stroke.”

Andreas J. Goss, chief executive, Siemens in the UK, said: “Stroke is the UK’s third biggest killer and contrary to popular belief it can affect people of any age. Siemens is delighted to be able to use our partnership with GB Rowing to help build awareness, raise much-needed funds for The Stroke Association and to encourage people to take up regular exercise as part of an overall healthy lifestyle. I’ll be doing my bit, and encouraging our employees to do the same so please visit the website and have some fun taking part in Stroke for Stroke 2010.”

Head of Corporate Fundraising at The Stroke Association, James Beeby said: “Each year an estimated 150,000 people in the UK will suffer a stroke. Stroke for Stroke is now in its third year and a campaign like this is integral to raising awareness of how regular exercise and lifestyle choices can help prevent a stroke. This year we are anticipating an even greater number of people to get involved and support The Stroke Association’s vital research into stroke prevention and treatment.”

Notes

Siemens Stroke for Stroke Week is supported by The Stroke Association. Full details and a link to the justgiving website can be found at strokeforstroke

About Siemens in the UK

Siemens was established in the United Kingdom 166 years ago. The company employs 18,402 people in the UK, including about 5,000 in the manufacturing sector.

Last year’s revenues were ВЈ3.7 billion. As a leading global engineering company, Siemens provides innovative solutions to help tackle the world’s major challenges, across the key industrial sectors of energy, industry, transport and healthcare.

Siemens has offices and factories throughout the UK, with its headquarters in Frimley, Surrey. Siemens is the High Performance Partner to GB Rowing through to 2012.

For more information, visit siemens/

About Nuffield Health

Nuffield Health is the UK’s largest healthcare charity, providing health and wellbeing services through its national network of over 200 hospitals, wellbeing centres, workplaces and local authority facilities.

Nuffield Health also has the largest network of physiotherapists outside the NHS.

Since 1957, Nuffield Health has helped millions by putting the quality of care and satisfaction of individuals at the heart of what it does.

Since 2008, it has been pioneering a new approach to consumer health by integrating fitness, prevention and cure across its different services and facilities under a single brand, governance and management structure.

Source
The Stroke Association

Stroke is a leading cause of hospital admission among older adults. Yet more hospital readmissions after stroke are for pneumonia or for heart disease than for another stroke, according to a study published in the June 2007 issue of the journal Stroke. This finding may alter the standard medical management of post-stroke patients.

“Few stroke patients survive five years without a readmission to the hospital. Common wisdom has been that patients who have had a stroke are likely to return to the hospital for treatment of another stroke. Our study found that, surprisingly, the most common reasons for readmission to the hospital were non-neurological, with pneumonia or other respiratory problem leading the list of reasons,” said the study’s first author, Dawn M. Bravata, M.D., Indiana University School of Medicine associate professor of medicine.

The researchers followed 2,603 stroke patients discharged from the hospital and found that more than half had died or been readmitted to a hospital at least once during the first year after discharge. And by five years out, almost 9 out of 10 stroke survivors had died or been readmitted to a hospital. These readmissions were more than twice as likely to be for pneumonia as for another stroke.

“Physicians treating stroke patients need to continue focusing on preventing a recurrence of stroke. We now see that, in addition, we should also be thinking about the other conditions that are causing hospital readmission in this vulnerable group,” she said.

Dr. Bravata, who is an investigator with the Center on Implementing Evidence-based Practice at the Roudebush VA Medical Center in Indianapolis, currently is working on a follow-up study to see whether certain interventions, such as pneumonia and influenza vaccinations, can lower hospital readmissions for stroke patients.

“These readmissions are an enormous burden on patients, families and the health-care system. We may have a previously unrecognized window of opportunity beginning when the patient is first hospitalized for stroke to decrease the likelihood for hospital readmission,” Dr. Bravata said.

###

In addition to Dr. Bravata, authors of the study were Shih-Yieh Ho, Ph.D.; Thomas P. Meehan, M.D.; Lawrence M. Brass, M.D.; and John Concato, M.D. At the time of the study, all authors were affiliated with Yale University, Qualidigm, and/or the Veterans Administration Connecticut Healthcare System.

Contact: Cindy Fox Aisen

Indiana University

In diabetic patients with hypertension, ACE inhibitors reduce the risk of developing diabetes-related kidney disease, independent of their effect in lowering blood pressure, reports a study in the December Journal of the American Society of Nephrology.

“Our results clearly show that an ACE inhibitor should always be used in patients with high blood pressure and diabetes, even when they have no evidence of renal or cardiovascular disease,” comments the study’s lead author, Dr. Piero Ruggenenti of Mario Negri Institute for Pharmacological Research in Bergamo, Italy.

The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) study included 1,204 patients with type 2 diabetes and high blood pressure. At the beginning of the study, none of the patients had any signs of kidney disease. They were randomly assigned to treatment with an ACE inhibitor, another type of blood pressure drug called a calcium channel blocker, a combination of an ACE inhibitor with a calcium channel blocker, or an inactive placebo. Rates of microalbuminuria-small amounts of the protein albumin in urine, the first sign of diabetic kidney disease-were compared between groups.

After an average of 31⁄2 years, patients who had good blood pressure control-regardless of which treatment they received-had lower rates of microalbuminuria. Patients taking the combination treatment had the greatest reduction in blood pressure and were less likely to require additional drugs to keep their blood pressure under control.

Taking an ACE inhibitor, alone or as part of the combination treatment, provided further protection against diabetic kidney disease. This was also the case for patients whose blood pressure remained high-as long as they were taking an ACE inhibitor, their microalbuminuria risk was similar to that of patients whose blood pressure was well-controlled. Dr. Ruggenenti points out, “Treatment with an ACE inhibitor was particularly important when the blood pressure was poorly controlled-as may happen in most diabetic patients with hypertension, despite the use of two, three, or even more drugs.”

About 30 percent of people with diabetes will go on to develop kidney failure, while even more may be at risk of premature death from cardiovascular disease. Eighty to ninety percent of patients with type 2 diabetes also have hypertension, a major risk factor for diabetic kidney disease. “Optimizing blood pressure control appears extremely important to reduce or prevent the risk of kidney failure or death for these patients,” says Dr. Ruggenenti.

All doctors who treat diabetes need to know about the protective benefits of ACE inhibitor treatment-especially primary care doctors who care for the vast majority of diabetic patients without kidney disease. “Early and effective treatment of hypertension is of paramount importance in people with diabetes, and ACE inhibitors should be the treatment of choice,” Dr. Ruggenenti concludes. “However, in most patients, an ACE inhibitor alone is not enough to achieve good control of arterial blood pressure-less than 130/80 mm Hg. In these patients, the doctor should also use other antihypertensive drugs, including a diuretic, in most cases, to achieve this target. Although using an ACE inhibitor is important, so is achieving the target blood pressure whenever possible.” For patients who can’t take ACE inhibitors, another class of drugs-the angiotensin II receptor antagonists-may be a valid alternative.

The ASN is a not-for-profit organization of 9,500 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases.

American Society of Nephrology (ASN)

1725 I St., NW, Ste 510

Washington, DC 20006

United States

jasn

At the request of the Nigerian government, the IAEA deployed a team of nuclear safety experts to secure and transport several potentially hazardous radioactive sources in the country. Staff from the AgencyВґs Nuclear Fuel Cycle and Waste Technology department (NEFW) traveled to several different locations within Nigeria to safely recover the radiological sources and ship them in transport containers for return to Canada or processing at a Nigerian waste facility. With widespread application in a variety of medical, industrial, and research applications, keeping people safe from any potential risk from neglected neutron sources is a high priority.

“In countries where there are few proper places for safe and secure storage of used radioactive materials, we help to make sure that potential danger is removed,” said Josef Neubauer, a nuclear engineer in NEFW, who managed the Nigerian repatriation project. “We make trips such as these on an almost monthly basis to recover disused material that could be inappropriately used.”

At the request of the Nigerian Nuclear Regulatory Authority (NNRA), the IAEA assembled a team of radiation recovery experts to pick up the sources in three locations around the country. The team travelled to two hospitals and a research centre over a weeklong period last July, and recovered sources that were formerly used for cancer treatment and an insect irradiation project. The seven high-activity sources were expired, but would have posed a public safety threat had anyone come into contact with them. A high degree of security was maintained during the mission, with police accompanying the transport of the sources at all times. NNRA staff and bomb squad staff also assisted the multinational team to recover the sources.

The mission was not without its challenges. In addition to difficulty in disassembling some of the units, the team encountered vehicle breakdowns, equipment delays, and traffic jams. At one recovery mission in a hospital, an unforeseen equipment delay forced the team to complete its task under the dark of night.

While some original radioactive source manufacturers agree to accept a sourceВґs return, there are cases when the cost of return is prohibitive or a company goes out of business. International support such as that provided by the IAEA can help countries to manage the import, use, and export of radioactive sources. When assistance is requested from Member States, the IAEA deploys experts and assistance to work in concert with a countryВґs regulatory authority on a case-by-case basis.

The IAEAВґs work in this area is focused largely in developing countries, and the Agency is in planning stages of broadening its global reach to respond to assistance requests in Africa, Asia and Latin America.

Background


The IAEA works in a coordinative role in recovery and repatriation cases such as these. In recent years, NEFW staff have managed an average of 8-12 visits to countries asking for assistance in recovering stray radioactive sources. Most of the time these visits are to developing countries. In a number of cases, the Agency contracts with original equipment providers and other experts to handle these recovery efforts. In Nigeria, for example, experts from two firms were contracted by the Agency to assist with the mission.

Nigeria has seen its stockpile of radioactive sources grow in recent years. With widespread applications in petroleum, medical, and manufacturing sectors, the country has taken efforts in recent years to improve its administration of radioactive sources. The country established NNRA, its regulatory body, in 2001.

###

Source: Press Office

International Atomic Energy Agency

The Institute of Cancer Research’s scientist, Dr Gerhardt Attard has just been awarded a Young Investigator Award by the Prostate Cancer Foundation (PCF) for his ongoing work into developing the prostate cancer drug abiraterone.

Designed to encourage the most innovative research thinkers to continue their careers in prostate cancer research, the awards provide recipients with $75,000 annually for three years to support specified research programs.

This year’s Young Investigator Awards represent a new $4.3 million commitment by the PCF to the global cancer research community.

Dr Attard’s award will be dedicated towards research at the London-based Institute into the inhibition of the hormone CYP17 by abiraterone, which is showing promising results in treating advanced prostate cancer.

Dr Attard says:

“I am deeply honoured by this award. The PCF’s contribution will help our team to carry out important work into understanding the mechanisms that cause resistance to hormone treatments, such as abiraterone. We have developed a test that allows us to identify and study circulating prostate-cancer cells and are using this to identify biological differences that exist between patients that respond to abiraterone and those that do not.

“We are also collecting and analysing these cells at regular intervals from patients on treatment with abiraterone acetate and are identifying changes in the cancer that make it resistant to hormone treatments.”

The 19 Young Investigator Award recipients were selected by an expert committee comprised of 25 leading scientists and clinicians.

“The response to the first year’s call for applicants was global, resulting in 76 applications from eight countries in North America, Europe and Asia,” commented Dr. Howard Soule, executive vice president and chief science officer for the PCF.

“The research proposals focused on 16 different prostate cancer research areas. The applicants represented seven medical and scientific disciplines including medical oncology, radiation oncology, urology, pathology, imaging science and many areas of molecular science. Supporting a focus on prostate cancer by talented, young investigators is critical to realizing the PCF’s goal of accelerating breakthrough discoveries that can potentially end death and suffering from prostate cancer.”

Information on the 2008 PCF Young Investigator Award recipients may be found here.

About abiraterone

Abiraterone was developed at The Institute of Cancer Research in London and works not only in blocking the generation of these hormones in the testes, but also elsewhere in the body, including generation of hormones in the cancer itself. Initial studies are showing that it is effective in treating up to 80 per cent of men with the most aggressive form of prostate cancer.

For more information please see our recent (press release )

About The Institute of Cancer Research

The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care.

For more information visit icr.ac .

The Institute is a charity that relies on voluntary income. The Institute is one of the world’s most cost-effective major cancer research organisations with over 95p in every ВЈ of total income directly supporting research.

About the Prostate Cancer Foundation

The PCF’s Young Investigator awards are inspired by Donald S. Coffey, PhD, prostate cancer research director at Johns Hopkins for 40 years. He has mentored more than 50 scientists and physician-scientists and trained more than 30 of today’s leading prostate cancer researchers. These awards provide career and project support for young (generally 35 and under), proven investigators who have already achieved junior faculty positions and are committing their lives to the field of prostate cancer.

The Prostate Cancer Foundation (PCF) is the world’s largest philanthropic source of support for prostate cancer research. The foundation’s primary goal is discover better treatments and a cure for recurrent prostate cancer. PCF pursues its mission by reaching out to individuals, corporations and others to harness society’s resources–financial and human–to fight this deadly disease that strikes one out every six men.

The Institute of Cancer Research

A new report issued by the International Osteoporosis Foundation (IOF) and published in the scientific journal Osteoporosis International1, shows that populations across the globe are suffering from the impact of low levels of vitamin D. The problem is widespread and on the increase, with potentially severe repercussions for overall health and fracture rates.

Compiled by IOF’s expert working group on nutrition, the report reviews the scope and causes of low vitamin D levels in six regions: Asia, Europe, Latin America, Middle East and Africa, North America and Oceania. Regional reports are available on the IOF website

Vitamin D is mainly produced in the skin upon exposure to sunlight, and, to a lesser extent, is derived from nutritional sources. It plays an important role, through its influence on calcium levels, in the maintenance of organ systems, and is needed for normal bone mineralization and growth. Suboptimal levels of vitamin D may lead to increased risk of osteoporosis and hip fracture and, in severe cases, to the development of rickets, a softening of bones in children that can lead to skeletal fractures and deformity.

Although there is ongoing debate as to what constitutes the optimal level of vitamin D, the report shows that regardless of whether it is defined at 50nmol/L or 75nmol/L, vitamin D status is seriously inadequate in large proportions of the population across the globe.

The main risk factors for low vitamin D levels include older age, female sex, lower latitudes, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and the absence of vitamin D fortification in common foods. Further factors include the increase in urbanization, where people tend to live and work indoors, as well as cultural practices that tend towards sun avoidance and the wearing of traditional clothing that covers the skin. The severity of the problem in Middle East and South Asia arises from the combination of several of these risk factors.

These findings suggest that prevention strategies must be initiated at the national level – especially given the increasing ageing of populations in many regions of the world. National plans of action should encourage safe, limited exposure to sunlight and improved dietary intake of vitamin D, whilst considering fortification of foods as well.

Notes:
1. A. Mithal, D.A. Wahl, J-P. Bonjour et al. on behalf of the IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D (2009) Osteoporosis International, in press.


2. Regional reports for Asia, Europe, Latin America, Middle East and Africa, North America and Oceania may be downloaded free of charge from the IOF website.

Source:
L. Misteli

International Osteoporosis Foundation

UroToday- Traditionally a number of hormonal, immunotherapeutic, and chemotherapy agents have been the basis of treatment in metastatic renal cell carcinoma (mRCC) however, they are typically associated with low response rates and considerable toxicity in patients that receive them. There is preclinical data that suggests the M2-affecting ribonucleotide reductase (RR) inhibitor Triapine® might be associated with anti-tumoral activity while demonstrating acceptable toxicity. Here, the authors report on the results of a single-arm, phase II clinical trial that examines the efficacy and toxicity of Triapine®.

In this trial 19 eligible patients with mRCC and without prior treatment received Triapine® in dosages of 96 mg/m2 x 4 days every two weeks with a four-week period constituting one cycle of treatment. The primary endpoint of the trial was response rate (RR) with secondary endpoints of progression free survival (PFS), overall survival (OS), and toxicity. Only 15 of the 19 patients were evaluable for response after the first treatment cycle. There was one PR, seven SD, and seven PD responses to regimen. The median PFS for this 15 patient group was 3.6 months and the median OS was 14.6 months. Toxicity was evaluated in all 19 patients. Of note, grade 3 toxicity was observed in fifteen patients (79%) which required the need for dose reductions.

The authors conclude that this treatment offers little efficacy and significant toxicity for mRCC. In fact, the study was stopped after stage 1 because the minimum efficacy criteria had not been met. Triapine® has some demonstrated activity in mRCC, but one might question the relevance of this finding in the setting of the more active targeted therapies currently used in mRCC.

Segota E, Mekhail T, Olencki T, Hutson TE, Dreicer R, Wacker B, Osterwalder B, Elson P, Zhou M, Bukowski RM

Urologic Oncology: Seminars and Original Investigations. 25(1):46-52, May 2007
doi:10.1016/j.urolonc.2006.02.016

Reported by UroToday Contributing Editor Christopher G. Wood, MD

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
www.urotoday

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Copyright © 2007 – UroToday
Reproduced for blog with permission of UroToday.
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Biologists at UC San Diego have identified the specific region in vertebrates where adult blood stem cells arise during embryonic development.

Their discovery, which appears in a paper in this week’s early online edition of the journal Nature, is a critical first step for the development of safer and more effective stem cell therapies for patients with leukemia, multiple myeloma, anemia and a host of other diseases of the blood or bone marrow.

The researchers say their time-lapse imaging of the process, by which primitive embryonic tissues first produce the parent stem cells that produce all adult blood cells over the life of an individual, should help guide future efforts to repair and replace this cell population for therapeutic purposes.

Current transplantation therapies rely on the infusion of donor stem cells into a patient’s bone marrow to generate new, healthy blood cells without disease. But that procedure is often risky and can result in fatal complications, due in part to “graft-versus-host disease,” in which transplanted cells react against foreign tissues of the recipient. One means of circumventing this immune rejection problem would be to generate hematopoietic stem cells, or HSCs, using the patient’s own precursor cells. Such cells would be perfectly genetically matched, but in order to generate such cells, scientists must first understand the molecular processes that underlie specification of HSCs.

“If we could generate healthy HSCs from patients and transplant them back into their own bone marrow, it would eliminate many complications,” said David Traver, an assistant professor of biology who headed the research team.

“Our findings are an important step toward this goal because they provide a better understanding of how HSCs, the cell type responsible for the clinical benefits of bone marrow transplants, are first specified during development,” he said. “This improved understanding will aid efforts to instruct pluripotent embryonic stem cells (ESCs), the stem cells that can produce all types of tissue-specific stem cells in the body, to make HSCs; something that is not currently possible. In other words, we are one step closer now to understanding how to clinically generate HSCs for cellular replacement therapies from ESCs.”

Traver and his colleagues, who included Julien Bertrand, a postdoctoral fellow in his laboratory, Neil Chi, an assistant professor of medicine at UCSD and Didier Stainier, a professor of biochemistry at UC San Franscisco, made their discoveries in zebrafish, a model laboratory organism for geneticists in which embryos are transparent, allowing the researchers to observe and track individual stem cells with a microscope.

A number of earlier studies using indirect observation had led to the idea that a particular region of the embryo surrounding the dorsal aorta, an early blood vessel, produced the first HSCs, but until now no one had been able to directly visualize the process in living animals.

“Indeed a number of conflicting studies had proposed different or earlier sites of origin, making the exact location where HSCs develop controversial,” said Traver. “Using zebrafish embryos with fluorescently labeled tissues, we were able to demonstrate that HSCs arise directly from cells lining the floor of the dorsal aorta by imaging the process in living embryos.”

The UCSD researchers also documented the stepwise formation of HSCs from “hemogenic” aortic endothelium and showed, by expressing a permanent fluorescent marker in these cells, that all adult blood and immune cell types derive from aortic endothelium of the early embryo.

“Our studies suggest that transition through a hemogenic endothelial intermediate is a requisite step for hematopoietic stem cell formation,” said Traver. “Based upon the high degree of evolutionary similarity in the regulation of HSC formation and later blood maturation in other vertebrates, this finding almost certainly applies to the development of HSCs in humans. These findings should, together with recent breakthroughs in making induced pluripotent stem cells (iPSCs), the functional equivalent of patient-specific ESCs, in principle allow the generation of replacement HSCs from unrelated adult tissues. This would enable repopulation of a patient’s hematopoietic system with his own, disease-free HSCs to avoid immune rejection.”

Other researchers involved in the study included Buyung Santoso and Shutian Teng of UCSD. The study was supported by grants from the National Institutes of Health and the California Institute for Regenerative Medicine.

Source:
Kim McDonald
University of California – San Diego