Team Designs Computer Model to Predict Pathways of Blood-Vessel
Model May Have Applications In Pharmaceutical Industry For Treatment
Of Heart Disease, Diabetes And Cancer
February 5, 2004 --
A team of researchers at the University of Virginia has
developed a complex computer model that can accurately predict
how and where
new blood vessels will form in response to two different stimuli:
changes in blood pressure and the delivery of a growth protein.
results — believed to be a first in the emerging field
of systems biology — hold promise for future developments
in the treatment of chronic heart disease and diabetes through
angiogenesis, or the growth of new blood vessels. The results
also could be used in the development of treatments for cancer
involve shutting off the blood supply to cancerous tissue.
method — using a complex, quantitative, predictive
model — also has the potential to speed up the development
of new medical treatments and should be of interest to the pharmaceutical
and medical-device industries.
pharmaceutical companies are investing heavily in computational
systems biology, and our study indicates they are on the
right track,” said Thomas C. Skalak, professor of biomedical
engineering at U.Va. and principal investigator. “Quantitative
biology holds the key to the medical discoveries of the future.”
U.Va. team’s findings will be released Feb. 6 in the
online edition of FASEB Journal, published for the Federation
of American Societies for Experimental Biology, at www.faseb.org.
An illustration of their work will appear on the cover of
print edition in April.
“To our knowledge, this is the first time that a computer model of a complex
biological system has accurately predicted how a network of new blood vessels
in response to specific stimuli,” Skalak said. “Experimental
observation verified our in silico results.”
past president of the Biomedical Engineering Society, and U.Va.
Shayn M. Peirce and Eric J. Van Giesen conducted
bioengineering research and co-authored the FASEB Journal article.
U.Va. researchers set out to answer two questions: 1) How are
blood vessels assembled on a cell-by-cell basis in mammals? and
2) How do
of individual cells to environmental stress or injury affect the
construction of single blood vessels and networks of blood vessels?
Their goal was
understand how a living, multicellular system grows and adapts
to various stimuli and, ultimately, to be able to engineer vascular
research team built on the work of Hungarian-born mathematician
John Louis von Neumann, borrowing his “Cellular
Automaton” theory, and used
Uri Wilensky’s NetLogo simulation software, developed at
Center for Connected Learning and Computer-Based Modeling, to
build a complex computer model that mimics blood-vessel growth
also drew on 50 rules of cellular behavior published by
other researchers for elements of their model. But no one had
all the pieces together
in the same way to answer those questions.
U.Va. researchers created a complex, “multicellular simulation” in
mammalian tissue, integrating data from thousands of individual
cells, including the endothelial cells and smooth-muscle cells
needed to build the blood-vessel
walls. Among the 50 factors the model considers for each
cell as it interacts with other cells are varied rates of cellular
growth and cellular migration in
space and over time. The model also takes into account the
dynamic environment of the surrounding tissue, which influences
the pace and direction of blood-vessel
researchers’ model predicted that
an increase in blood pressure would stimulate cells to
build blood vessels with a larger diameter, increasing the
delivery of oxygen through an expanded blood flow; and
that the delivery of a growth protein would stimulate cells to
build longer blood vessels, extending
the reach of the blood flow through an expanded network
research into microvascular remodeling has multiple applications
in the fields of tissue engineering,
and reparative medicine, according to Skalak. In particular,
results may contribute
to the development
of processes to help the body heal itself after heart
disease or traumatic injury, or help with the creation of in
systems to grow new tissue
lost to injury or disease.
addition, the U.Va. team is investigating the impact of other
stimuli on blood vessel
growth, on vascular
cellular and tissue cohesion.
U.Va. research is funded in part by the National Institutes of
Health and by the
a private, nonprofit
Va., which is dedicated to improving human health
through support for biomedical engineering.
Department of Biomedical Engineering at the University of Virginia
is a joint,
of the School of Medicine
and the School
and Applied Science.
For more information about the research, call Thomas
Skalak, chairman of the Department of Biomedical
or contact him by
email at email@example.com.
Charlotte Crystal, (434) 924-6858