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Topic Name: A discovery in mice of immune cells that promote the formation of new blood vessels

Category: Genetic Engineering

Research persons: Ofer Fainaru, MD, PhD,Judah Folkman, MD

Location: Boston, United States

Details

A discovery in mice of immune cells that promote the formation of new blood vessels could lead to new treatments for endometriosis, a painful condition associated with infertility that affects up to 15 percent of women of reproductive age.

The formation of new blood vessels, or angiogenesis, is known to encourage the growth of tumors and endometriosis lesions.

A team led by Ofer Fainaru, MD, PhD, a research associate in the Vascular Biology Program at Children's Hospital Boston and Harvard Medical School, found that dendritic cells -- highly specialized immune cells -- help trigger angiogenesis in a mouse model of endometriosis. Their findings were published online last month in the FASEB journal. Judah Folkman, MD, director of Children's Vacular Biology Program, who helped found the field of angiogenesis, was the paper's senior author.

Endometriosis occurs when endometrium, a tissue normally found in the inner lining of the uterus, grows elsewhere in the body -- most commonly in the abdominal cavity. The misplaced endometrial tissue begins as small lesions, or masses, but once blood vessels are recruited, the lesions grow larger and respond to female hormones, resulting in inflammation, cyclic pelvic pain, and infertility.

In the mouse model, the researchers observed that dendritic cells infiltrate endometriosis lesions, and near the sites where they invade, new blood vessels form. Injecting mice with excess dendritic cells caused their lesions to gain more blood vessels and to grow larger.

The researchers also found that dendritic cells have a strikingly similar effect on intra-abdominal tumors.

When the researchers grew dendritic cells together with endothelial cells -- the cells that line blood vessel wall -- the endothelial cells migrated towards the dendritic cells. The team hypothesizes that dendritic cells, after embedding in a new lesion or tumor, act like foremen on a building team: they call in, direct and support endothelial cells that build the new blood vessels.

"We believe that targeting dendritic cells may prove to be a promising strategy for treating conditions dependent on angiogenesis, such as endometriosis and cancer," says Fainaru. But first, the team must demonstrate that dendritic cells are essential -- that without these cells in mice, new blood vessels do not form.

"Our next step would be to look for specific dendritic cell inhibitors that could have the potential to block angiogenesis in these conditions," says Fainaru.

The team hopes to develop cell-specific therapy for angiogenesis-dependent diseases that will be more effective and less toxic than current treatments. Currently, the most effective treatment for endometriosis is surgically removing the lesions, but this does not prevent them from growing back -- as large and symptomatic as before. If dendritic cells are indeed ringmasters and not sideliners in new blood vessel growth, locally knocking them out just after an initial surgery, or altering them in some way, could render the lesions tiny and harmless.

Similarly, potential dendritic-cell inhibitors, when added to other agents that stop new blood vessels from forming, could enhance doctors' ability to choke off growing tumors, Fainaru adds.

The study was funded by the Fulbright Foundation, the Rothschild Foundation, the National Institutes of Health, and the Breast Cancer Research Foundation.

About Researchers:

Judah Folkman, MD

About funds:

The National Institutes of Health (NIH)

The National Institutes of Health (NIH) is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical research.

The Institutes are responsible for 28%—about $28 billion—of the total biomedical research funding spent annually in the U.S., with most of the rest coming from industry.[1] The NIH is divided into two parts: the "Extramural" parts of NIH are responsible for the funding of biomedical research outside of NIH, while the "Intramural" parts of NIH conduct research. Intramural research is primarily conducted at the main campus in Bethesda in unincorporated Montgomery County, Maryland, and the surrounding communities. The National Institute of Aging and the National Institute on Drug Abuse are located in Baltimore, Maryland, and the National Institute of Environmental Health Sciences is in Research Triangle, North Carolina. The NIAID maintains Rocky Mountain Labs in Hamilton, Montana,[2] with an emphasis on virology.

The predecessor of the NIH began in 1887 as the Laboratory of Hygiene. It grew and was reorganized in 1930 by the Ransdell Act into the National Institute of Health (singular at the time). Today it is one of the world's foremost medical research centers, and the Federal focal point for medical research in the U.S. The NIH, comprising 27 separate institutes, centers and the Office of the Director, is part of the United States Department of Health and Human Services. The current NIH Director is Elias Zerhouni.

The goal of NIH research is to acquire new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold. The NIH mission is to uncover new knowledge that will lead to better health for everyone. NIH works toward that mission by: conducting research in its own laboratories; supporting the research of non-Federal scientists in universities, medical schools, hospitals, and research institutions throughout the country and abroad; helping in the training of research investigators; and fostering communication of medical and health sciences information.

International Breast Cancer Research Foundation

The International Breast Cancer Research Foundation is a New York-based international organisation that works on breast cancer issues around the world. It argues that "only through practical, cost-effective breakthrough research that takes advantage of the most promising opportunities and ideas everywhere in the world can we reach our goal of ending the suffering and death caused by breast cancer."

According to this organisation, some one-and-half million women worldwide are diagnosed with breast cancer each year.

IBCRF was founded in 1992. Its current (July 2007) scientific director is Dr. Richard Love of the Ohio State University.

JUDITH ROTHSCHILD Foundation

Judith Rothschild, who died at the age of 71 in 1993, was a noted abstract painter whose work was exhibited widely in the United States and abroad. A graduate of Wellesley College, Rothschild studied painting at the Cranbrook Academy of Art, at the Art Students League with Reginald Marsh, at Stanley William Hayter's Atelier 17, and with Hans Hofmann and Karl Knaths. She was a member and later president of the American Abstract Artists, a member of the Jane Street Gallery, and an editor of Leonardo magazine. Ms. Rothschild was deeply interested in the careers of fellow artists and sought to create and share opportunities for advancement with them. For instance, she joined with several fellow artists to form the cooperative Long Point Gallery in Provincetown, on Cape Cod. It is in this spirit of cooperation and support that The Judith Rothschild Foundation was created by her will, based on her belief that the life's work of meritorious artists should be preserved and made accessible to future generations.

As a further reflection of her commitment to arts organizations and to the importance of contributing the insights of a working artist, Rothschild actively served at various times as a trustee of The American Federation of Arts, The MacDowell Colony, The New York Studio School, The Fine Arts Work Center in Provincetown, and on committees of the Pennsylvania Academy of the Fine Arts, the Philadelphia Museum of Art, and the Wellesley, Williams, and Bard College art museums.

Judith Rothschild worked in oils and collage and began her relief paintings in the early 1970s; the reliefs combine figurative elements with an abstract sign language, wedding sensual color to austere formal structures. Her work is included in the collections of many museums, such as the Metropolitan Museum of Art, the National Gallery of Art, The Museum of Modern Art, the San Francisco Museum of Modern Art, the Solomon R. Guggenheim Museum, the Whitney Museum of American Art, the Philadelphia Museum of Art, the Baltimore Museum of Art, the Sammlung Ludwig Museum in Aachen, The Neuberger Museum, the Corcoran Gallery of Art, the Fogg Art Museum, and the Smith and Wellesley College art museums.