A step toward tissue-engineered heart structures for children
Delicate valves and patches grow with the child
September 10, 2007
Virna Sales, MD
Infants and children receiving artificial heart-valve replacements
face several repeat operations as they grow, since the replacements
become too small and must be traded for bigger ones. Researchers at
Children's Hospital Boston have now developed a solution: living,
growing valves created in the lab from a patient's own cells.
In a special issue of Circulation published September 11, they
describe making pulmonary valves through tissue engineering. These
valves, which provide one-way blood flow from the heart's right
ventricle into the pulmonary artery, are often malformed in
congenital heart disease, putting an extra burden on the heart.
"The heart valve is a complex organ," says Virna Sales, MD, a
researcher in Children's Department of Cardiac Surgery and the
study's first author. "It must open and close synchronously,
withstand pressure, and be pliable and elastic. We are one of the few
labs in the U.S. that's attempting to make heart valves through
tissue engineering. We hope these could just be implanted in a child
just once, instead of the many heart operations most children have to
go through as they get older."
The researchers, led by Sales and senior investigator John Mayer, MD,
in Children's Department of Cardiac Surgery, first isolated
endothelial progenitor cells (precursors of the cells that line blood
vessel walls) from the blood of laboratory animals. They
then "seeded" the cells onto tiny, valve-shaped biodegradable molds
and pre-coated with proteins found in the natural "matrix" that
surrounds and supports cells.
Experimenting with different matrix proteins and growth factors, they
were able to make pulmonary valve leaflets that had the right
mechanical properties -- sturdy yet pliable. Tests showed the
original cells had differentiated to form both endothelial cells and
smooth-muscle-
them together.
With grants from the American Heart Association and the Cambridge,
Mass.-based Center for Integration of Medicine and Innovative
Technology (CIMIT), Sales is now refining the lab-grown valves by
exposing them to mechanical stress in a bioreactor. She is also using
a "cardiac jelly" -- a cushiony material rich in matrix components
and growth factors -- to encourage cells to differentiate and form a
heart valve on their own, with only minimal reliance on an artificial
scaffold. "I would like to mimic what really happens in the embryo --
what Mother Nature does," she says. The next step would be to implant
the living valves into animals.
Sales and surgical research fellow Bret Mettler, MD, have already
used tiny tissue-engineered patches in sheep to rebuild a portion of
the pulmonary artery -- an area that often needs augmentation in
patients with congenital heart disease. Eventually, Sales hopes to
use tissue-engineering techniques to create "living stents" for
adults with atherosclerosis. The current study was funded by the
National Institutes of Health, a grant from the U.S. Department of
Commerce's National Institute of Standards and Technology program
(via Tepha, Inc., Cambridge, Mass.), the Gross Cardiovascular Fund,
CIMIT, the National Science Foundation, and an American Heart
Association National Scientist Development Grant awarded to Sales.
Contact:
Anna Gonski
617-355-6420
anna.gonski@
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, 11 members of the Institute of Medicine and 10 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 347-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. For more information
about the hospital and its research visit:
www.childrenshospit
http://www.children
evel342.html
More:
http://www.medgadge
s_that_grow_
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