Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem cells used to model infant birth defect

19.03.2010
Findings reveal why a longstanding treatment works, and suggest better approaches

Hemangiomas -- strawberry-like birthmarks that commonly develop in early infancy -- are generally harmless, but up to 10 percent cause tissue distortion or destruction and sometimes obstruction of vision or breathing.

Since the 1960s, problematic hemangiomas have been treated with corticosteroids such as dexamethasone or prednisone. But steroids have considerable side effects, don't always work, and their mechanism of action in hemangioma has remained a mystery.

Researchers at Children's Hospital Boston recently discovered that infantile hemangiomas originate from stem cells, and have used these stem cells to better understand this tumor in the laboratory. In the March 18 issue of The New England Journal of Medicine, they show that steroids target hemangioma stem cells specifically, reveal their mechanism of their action and suggest other possible ways to halt and shrink hemangiomas.

Hemangiomas, affecting 4 to 10 percent of infants, are noncancerous tumors consisting of a tangled mass of blood vessels. Previously, it was assumed that steroids act on endothelial cells, which make up about 30 percent of cells in the tumor. The new research, led by dermatologist Shoshana Greenberger, MD, PhD, working in the lab of Joyce Bischoff, PhD, in Children's Vascular Biology Program, shows that steroids interfere with a much rarer and more primitive cell type - hemangioma stem cells.

Greenberger and Bischoff further showed that steroids work by inhibiting hemangioma stem cells' ability to stimulate blood vessel growth, and that they do so by shutting down production of a specific factor called vascular endothelial growth factor (VEGF-A). VEGF is well known as a stimulator of angiogenesis (blood vessel growth) in cancer and age-related macular degeneration.

"We now have more therapies targeting VEGF, so our findings open the way to finding a more specific and safer therapy for hemangioma," says Greenberger.

Steroids usually result only in stabilization of hemangioma growth, and about 30 percent of hemangiomas don't respond to steroid treatment. Steroids also have side effects including facial swelling, hyperactivity, growth retardation and increased blood pressure. Although the effects on appearance may seem minor, research indicates that a baby's physical appearance can interfere with maternal bonding.

"My dream has always been to give a drug to stop hemangioma at its first appearance," says Children's plastic surgeon John Mulliken, MD, co-director of Children's Vascular Anomalies Center and a co-author on the study.

Greenberger, Bischoff and colleagues worked with hemangioma stem cells isolated from patient tissue samples provided by Mulliken, and showed that:

When human hemangioma stem cells were pretreated with dexamethasone, then implanted in mice, the tumors that formed had far fewer blood vessels.
Dexamethasone suppressed the stem cells' production of VEGF-A, but did not suppress VEGF-A production by endothelial cells from the same hemangioma.
When VEGF-A production was suppressed in hemangioma stem cells using shRNA silencing, then implanted in the mice, there was an 89 percent reduction in vessel growth.

VEGF-A was detected in actively growing hemangiomas, but not in regressing (involuting) hemangiomas.


Earlier research in Bischoff's lab and that of Bjorn Olsen, MD, PhD, of the Harvard School of Dental Medicine, indicates that hemangiomas may result from an in utero mutation in a stem cell destined to become an endothelial cell, causing a disruption in the normally well-ordered process of blood vessel development. Under a 2008 Translational Research Program grant from Children's, Bischoff's lab has been using hemangioma stem cells to test a library of existing medications that might specifically inhibit the proliferation of the hemangioma stem cells, and thereby limit growth of the hemangioma tumor.

"Steroids are inhibiting expression of a central regulator of blood vessel growth: VEGF-A," says Bischoff. "But we'd like to target the stem cell itself - stop its proliferation, prevent it from differentiating into unwanted blood vessels and, at the same time, eliminate the cellular source of VEGF-A."

The study was funded by the National Institutes of Health, the Translational Research Program at Children's Hospital Boston, a Harvard Skin Diseases Pilot Study Grant, Sheba Medical Center (Israel), and the John Butler Mulliken Foundation.

Citation: Greenberger S, Boscolo E, Adini I, Mulliken J and Bischoff J. Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells. N Engl J Med 2010 Mar 18; 362(11):30-38.

Contact:
Keri Stedman
617-919-3110
keri.stedman@childrens.harvard.edu
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 13 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School.

Keri Stedman | EurekAlert!
Further information:
http://www.childrenshospital.org/
http://www.harvard.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>