Two-way signaling from two sets of blood cells is required for the balancing act.

Julian Martinez-Agosto, UCLA

When it comes to the body’s blood supply, maintaining the right balance is crucial. UCLA stem cell scientists have now discovered that in the common fruit fly, this balancing act requires a complex “conversation” involving more parties than originally thought.

In a new study, they show that two-way signaling from two different sets of cells is necessary for blood-supply balance, both to ensure that enough blood cells are produced to respond to injury and infection and that blood progenitor cells remain available for future needs.

In one of these signaling conversations, the stem cell-like blood progenitor cells, which contribute to the cells of the blood in the fruit fly Drosophila, receive signals from other cells that live in a nearby safe zone, known as a “niche.” These signals keep the progenitors in a stem cell-like state so that, when needed, they can begin differentiating into blood cells.

And in a startling discovery, the scientists found that the progenitor cells also receive critical signals back from the daughter blood cells they create, telling the progenitors when enough cells have been made and it’s time to stop differentiating.

The discovery of this “back talk” from the daughter blood cells was published Dec. 23 in the peer-reviewed journal Cell.

“The cells in the niche provide a safe environment to support blood progenitor cells,” said co-senior author Dr. Julian A. Martinez-Agosto, an assistant professor of human genetics and pediatrics and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “When the blood progenitor cells receive signals from the niche cells, it creates an environment for those cells to maintain their potential and not differentiate.”

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UCSF part of major research initiative to improve safety, effectiveness of blood transfusions.

Edward Murphy, UC San Francisco

UC San Francisco and its affiliate Blood Systems Research Institute (BSRI) have been awarded nearly $33 million in research contracts for four projects as part of a major new research initiative designed to improve the safety and effectiveness of blood transfusions in the United States and abroad.

Suported by the National Institutes of Health (NIH) National Heart, Lung and Blood Institute, the multicenter collaboration project, titled “Recipient Epidemiology and Donor Evaluation Study III (REDS-III),’’ will span seven years.

“For decades, transfusion safety research has focused on blood donors and infectious disease testing — now for the first time, we will be looking at the patients who receive blood transfusions,’’ said Edward L. Murphy, M.D., M.P.H., professor in the UCSF Departments of Laboratory Medicine and Epidemiology/Biostatistics and senior investigator with the BSRI.

More than five million patients in the United States undergo transfusion therapy annually.

REDS-III will entail the creation of four “hubs,’’ each consisting of a regional blood center and affiliated hospitals. The San Francisco hub will involve the Blood Centers of the Pacific, UCSF Medical Center, San Francisco General Hospital & Trauma Center, and the San Francisco Veterans Administration Medical Center. Blood Centers of the Pacific supplies more than 90 percent of the blood used by the three hospitals.

One of the new projects will focus on improving the practice of blood transfusion and evaluating the positive and negative effects of blood transfusion in the hospital setting. As many as 200,000 patients annually at the assorted hubs who receive blood transfusions, and up to 500,000 blood donors a year will be studied to determine, among other things, pulmonary edema after transfusion, transfusion-related lung injury, alloimmunization and other immunological effects of transfusion, Murphy said.

Another project will look at use of plasma, currently thought to be overused for clotting disorders, Murphy said.

UCSF and BSRI also feature prominently in the international component of the initiative:  collaborative research will be conducted in Brazil and South Africa (Johns Hopkins will partner with China for the third site). International projects will focus on prevention of transfusion-transmitted infectious diseases such as HIV, dengue virus and Chagas disease. The researchers also will study obstetric hemorrhage and increased recruitment of black blood donors in South Africa as well as the treatment and genetics of sickle cell disease in Brazil.

BSRI was additionally awarded the contract for a central laboratory that will provide laboratory support and expertise to the seven clinical centers in the U.S. and overseas.

“One of the things that enabled these projects to occur is the partnership between UCSF and BSRI,’’ said Murphy. “The collaborative culture of UCSF has helped enormously.’’

The project will also use resources of the UCSF Clinical and Translational Sciences Institute.

The overall research initiative totaling $87.2 million is funded by the NIH’s National Heart, Lung, and Blood Institute (NHLBI). The research program will build upon and extend the findings of prior projects that began in 1989 in response to the emerging HIV/AIDS epidemic. As the risk of transfusion-transmitted HIV, Hepatitis B and C viruses and West Nile virus has diminished, REDS-III will shift focus toward several new research areas including health outcomes in transfused patients, health screening of blood donors and even genetic studies in the blood bank setting.

“This research effort will protect both blood donors and recipients from existing and future risks, benefitting both the United States and countries struggling to ensure blood safety and availability,’’ said Susan B. Shurin, MD, acting director of the NHLBI.

Murphy said that the nature of blood transfusions has changed dramatically in recent decades since the advent of HIV.

“Before then, physicians used to transfuse much more liberally,’’ he said. “But HIV and other diseases changed transfusion practice — blood should be given based upon evidence-based guidelines, not just because there is a drop in hemoglobin.’’

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UCLA’s blood and platelet collection suffers a nearly 90 percent drop in summer.

UCLA’s Blood and Platelet Center provides the blood and platelet products needed for organ transplants, oncology, trauma injuries and other life-threatening conditions. Every single blood donation has the potential to save a life, said Laura Pinner, the center’s campus donor recruiter.

But when school lets out and summer begins, blood and platelet collection at the center suffers nearly a 90 percent drop. That’s why the center relies on staff and faculty to roll up their sleeves and pick up the slack.

Since 1975, the center has collected blood, platelets, plasma and cryoprecipitate (a product made from unusable plasma) on behalf of UCLA’s Westwood and Santa Monica hospitals. “It’s going right here in the community,” Pinner emphasized. “The hospitals are so close,” she said, pointing out that these are the hospitals most likely to care for members of the campus community in the case of an accident, injury or an urgent medical problem.

Today, the Blood and Platelet Center supplies 80 percent of the blood and platelet products needed at UCLA’s two hospitals. “On average, we transfuse a total of about 80,000 components annually,” said Dr. Shan Yuan, assistant medical director of transfusion medicine. A component comprises all the by-products available from one donation. From July through August, however, the less populated campus contributes only about 10,000 components.

Aside from the summer decline, there is a constant need for blood and platelets, because, as Pinner explained, “Blood — and plasma — doesn’t last forever once it leaves your body. Blood has a shelf-life of about a month, and platelets have a shelf life of about a week.” As a result, the center needs many and frequent donors.

On top of the inner satisfaction that a donor gets from giving, donations never go unrewarded. The center offers various gifts to get staff and faculty involved. Not only are donors granted the opportunity to flaunt a hero sticker and a brightly colored bandage of their choice, but staff and faculty donors can choose from a wide range of gifts — four hours of compensatory time, meal vouchers, movie tickets or gift cards for the student store. Also, as an added bonus until Sept. 16, donors are being offered Blood and Platelet Center cooler bags.

Staff and faculty can stop by on their lunch breaks or between classes since it typically takes only 45 minutes to donate blood. There are two locations to donate: at 1045 Gayley Ave., two blocks north of Wilshire Boulevard between Kinross and Weyburn avenues, and on the “A” level of Ackerman Union on campus.

“As someone with heart disease, who was once on the heart transplant list here at the UCLA Medical Center, I personally know the importance and life-saving capacity of donating blood with the UCLA Blood and Platelet Center,” said Pinner, who was on the list in 2001, but no longer is. “I myself would be relying on those donors.”

To donate blood, or for additional information, call (310) 825-0888, Ext. 2, or e-mail gotblood@ucla.edu. Drop-ins without appointments are also welcome at both centers.

UC San Diego leads a new national program to futher develop the science of glycobiology.

Ajit Varki, UC San Diego

Scientists at the University of California, San Diego, School of Medicine have received a major seven-year, $18 million grant to begin translating emerging discoveries in the field of glycosciences into new discoveries and therapies related to heart, lung and blood diseases.

Glycobiology is the study of glycans (carbohydrate chains) and their crucial roles in molecular and cellular biology. The grant from the National Heart, Lung and Blood Institute (NHLBI) under its new “Program of Excellence in Glycosciences” (PEG) will be headed by Ajit Varki, M.D., professor of medicine and cellular and molecular medicine and co-director of UC San Diego’s Glycobiology Research and Training Center (GRTC). A key component of the grant will be to train new generations of scientists who understand glycans. It will be led by Jeff Esko, Ph.D., professor of cellular and molecular medicine and the other co-director of the GRTC.

The NHLBI program highlights the growing importance of glycans in heart, lung and blood disease research. The PEG grant has several goals: To train future generations of scientists fluent in both glycan chemistry and biology; to facilitate national collaborations; to disseminate important research findings; and to develop and expand core facilities across the country devoted to supporting the diverse endeavors of glycoscience. Because of its well-established presence and prominence in the field, UC San Diego School of Medicine and the GRTC have been selected by NHLBI to take the lead role in coordinating the program interactions among the new PEG-funded institutions, which include Harvard University, the Cleveland Clinic and Johns Hopkins University.

“We are particularly well-suited for this role,” said Varki, who is also executive editor of the major textbook on glycobiology. “The GRTC is one of the few such centers in the world. And there’s an entrepreneurial spirit here at UC San Diego that’s rare and special. It encourages researchers to come together and collaborate in ways not seen elsewhere.”

Glycans are sugar molecules ubiquitously found on the surfaces of all mammalian cells, where they typically interact with other molecules to influence a wide variety of cellular activities, including immune system function, inflammation, angiogenesis and a variety of disease processes.

“In the past, glycans were not an integral part of molecular biology studies because they were more difficult to analyze,” said Varki, whose recent published work has linked glycans called sialic acids to inflammation and the biology of cancer and diabetes. “However, they are important molecules in all biological systems and the technology is now here to integrate them fully. Following the earlier lead of the National Institute of General Medical Sciences and the National Cancer Institute, the NHLBI has now established this special PEG program to recognize and support this transition.”

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Donors will receive baseball tickets, chance to be on field during practice.

UC Irvine Healthcare and Angels Baseball are partnering in a series of blood drives at Angel Stadium this summer to increase the supply for people in need at Orange County’s only Level I trauma center.

Blood reserves tend to run low during the summer. Seriously injured patients at UC Irvine Medical Center – which annually treats half of the county’s trauma victims – and newborns in its neonatal intensive care unit are particularly vulnerable to shortages.

Donors will get vouchers that can be exchanged at the stadium box office for two tickets to a future Angels game, valid on select dates. In addition, they’ll be entered in a drawing after every blood drive for four people to watch Angels batting practice from the field before a specified game. Winners – who will be notified by email within 48 hours of donating blood – will each receive an Angels goodie bag and four tickets to that game.

Donors must be at least 17 years old and may give blood only once every 56 days. They should be able to spend 45 minutes or so at the stadium on the day they donate.

Blood drives will take place in UC Irvine’s bloodmobile, which will be parked near the stadium ticket office and the giant red Angels caps on the following days:

• June 22: 10 a.m.-4 p.m.
• June 28: 8 a.m.-2 p.m.
• July 5, 20 and 30: 8 a.m.-2 p.m.
• July 14: 10 a.m.-4 p.m.
• Aug. 4 and 20: 8 a.m.-2 p.m.
• Aug. 10 and 30: 10 a.m.-4 p.m.
• Sept. 6: 8 a.m.-2 p.m.

After donating blood, participants can walk over to the ticket booth and exchange their vouchers for game tickets. The Angels have set aside certain sections from which to choose seats. The box office is open from 9 a.m. to 5:30 p.m. Monday through Saturday when the Angels are out of town or not playing and until the seventh inning on game days.

To make an appointment to donate, click on www.healthcare.uci.edu/BloodDrive, complete the online form and submit it. Check the website for additional rules about who can donate. For more information, contact UC Irvine at donateblood@uci.edu or 714-456-LIFE (714-456-5433).

About UC Irvine Medical Center: Orange County’s only university hospital, UC Irvine Medical Center offers acute- and general-care services at the new, 482,000-square-foot UC Irvine Douglas Hospital and is home to the county’s only Level I trauma center, American College of Surgeons-verified regional burn center and National Cancer Institute-designated comprehensive cancer center. U.S. News & World Report has included UC Irvine for 10 consecutive years on its list of America’s Best Hospitals, giving special recognition to its urology, gynecology, and ear, nose & throat programs.

It was the call every blood donor longs to receive, but almost never does: Come in and meet the patient who benefited from your donation.

“Blood’s a funny thing. It tells a story.” – “CSI: Miami”

October 2003: A Barstow man struggling to breathe was airlifted over the San Bernardino Mountains to UC Irvine Medical Center. On-site physicians quickly determined he had acute respiratory distress syndrome (ARDS) – his lungs were not providing enough oxygen to the blood – but they didn’t have a clue why.

So they contacted Dr. Jae Chang, blood detective. “Give me 24 hours to see what I can do,” he remembers saying.

A UCI hematologist, Chang specializes in treating patients with complex and hard-to-diagnose blood disorders, the kind requiring the experience, intellect and well-trained eye of a grizzled crime-scene investigator.

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