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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>