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MGH research team grows long-lasting
blood vessels
Advance could solve major challenge
in tissue engineering
BOSTON - March 10, 2004 - Researchers from Massachusetts
General Hospital (MGH) have successfully induced the growth of new
networks of functional blood vessels in mice. In the March 11 issue
of Nature, the team from the Steele
Laboratory in the MGH Department of Radiation Therapy describes
how their technique led to the growth of long-lasting blood vessels
without the need for genetic manipulation. The accomplishment may
help solve one of the primary challenges in tissue engineering:
providing a blood supply for newly grown organs.
"The biggest challenge has been making blood vessels that will
last," says Rakesh Jain, PhD, director of the Steele Laboratory
and senior author of the Nature report. "Most artificially
grown vessels die quickly, but these have survived successfully
for a year - which is about half a lifetime for mice." He and
his colleagues also note that the introduction of genes to induce
vessel growth and survival could increase the risk of cancer.
The research team began with two types of blood-vessel-related human
cells - endothelial cells that form the lining of blood vessels,
taken from the veins of umbilical cords, and precursors to the perivascular
cells that form the supporting outer layer of blood vessels. These
cells were placed into a collagen gel and grown in culture for about
a day. Then the gels were implanted into cranial windows, transparent
compartments placed on the brains of mice. Similar gels containing
only endothelial cells were also prepared and implanted.
Within a few days both types of implants began to form long, branched
tubes. Tubes in the endothelial/perivascular cell implants soon
connected to the mice's own vessels and began to carry blood. They
grew rapidly for about two weeks, and then reached a point of stability.
However, implants containing only endothelial cells showed little
or no connection to the mouse vasculature, and within two months
the new vessels in those implants almost completely disappeared.
"The combined implants formed beautiful networks that survived
and grew," Jain says. "As they matured, they appeared
and functioned very much like normal vasculature tissue." Jain
is Cook Professor of Tumor Biology at Harvard Medical School.
The researchers believe their technique could eventually allow the
growth of new blood vessels from a potential recipient's own cells
and could also be a model system for future studies of vessel growth
and maturation.
The study's co-authors are Naoto Koike, MD, PhD; Dai Fukumura, MD,
PhD; Oliver Gralla, MD, and Patrick Au, all of the Steele Laboratory;
and Jeffrey Schechner, MD, of Yale School of Medicine. The research
was partially supported by the National Cancer Institute.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $400 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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