Cell combo yields blood vessels
Technology Research News
of the main challenges to growing replacement organs is finding ways to
get blood vessels to form inside the tissue before it is placed inside the
Researchers have been remarkably successful in recent years at growing
different types of tissue, but getting relatively large pieces of engineered
tissue to survive in the body requires coaxing networks of tiny blood vessels
to form as the tissue grows in the laboratory.
Researchers from the Massachusetts Institute of Technology, Twente
University in The Netherlands, Brigham and Women’s Hospital, Massachusetts
General Hospital, the Boston Children’s Hospital, the Schepens Eye Research
Institute, and Harvard Medical School have brought tissue engineering a
significant step forward with a method for growing muscle tissue that contains
blood vessels. They also showed that tissue grown using the method survives
better in mice and rats than tissue formed using previous techniques.
The technique paves the way to growing viable, vascularized tissue
from cells. "In vitro vascularization can improve vascularization in vivo
and survival of the implant," said Shulamit Levenberg, a former research
associate at the Massachusetts Institute of Technology and now a senior
lecturer at Technion-Israel Institute of Technology in Israel.
This is needed to realize the long-held dream of growing replacement
parts like muscles and internal organs.
The key to the breakthrough was seeding several types of cells on
a three-dimensional scaffold to form skeletal muscle tissue, said Levenberg.
Tissue engineering involves seeding a scaffold with thousands of
cells that are precursors to the specialized cells of particular types of
tissue. The scaffolds are sponge-like polymer materials that degrade over
time as the tissue forms.
Efforts aimed at growing muscle tissue usually begin with myoblast
cells, which fuse together to form skeletal muscle fibers. Skeletal muscle
fibers arranged in parallel and linked by connective tissue form skeletal
muscle tissue, which attaches to the skeleton and moves the body.
The researchers added two other types of cells to the process --
endothelial and fibroblast -- with the aim of promoting blood vessel growth
as the tissue forms. Endothelial cells form the inner lining of blood vessels
throughout the circulatory system. Fibroblasts are the precursors to connective
tissue cells. The endothelial cells and fibroblasts were derived from human
embryonic stem cells.
When the researchers combined myoblasts and endothelial cells in
the scaffold, they found that the endothelial cells organized themselves
into blood vessels within the growing tissue. When the researchers used
all three types of cells, the fibroblasts formed smooth muscles cells around
about 65 percent of the blood vessels, which stabilized the vessels.
The researchers implanted tissue grown for two weeks in the laboratory
under the skin of mice, within the quadriceps muscle of rats, and as a replacement
of a segment of abdominal muscle in mice. The precursor cells continued
to form muscle, blood vessel and connective tissue cells in all three types
of implants, according to the Levenberg.
Two weeks after implantation many of the engineered blood vessels
had connected to the host animal's native blood vessels, and about 40 percent
carried blood from the host, according to Levenberg.
Implanted tissue grown with the researchers' technique yielded about
30 functional blood vessels per square millimeter compared to about 20 in
tissue grown from muscles cells only, according to Levenberg. The blood
vessels in the researchers' tissue were also larger, she said.
The research shows that forming blood vessels in engineered tissue
improves the vascularization and survival of tissue implants, and that using
multiple types of seed cells is important for forming the blood vessels
in the tissue, said Levenberg.
The researchers' next steps are to apply the technique to other
types of tissue and to use the method to produce vascularized tissue implants
that function rather than simply survive inside the body.
Levenberg's research colleagues were Jeroen Rouwkema and Clemens
A. van Blitterswijk of Twente University in The Netherlands, Mara Macdonald,
Robert Marini and Robert Langer of the Massachusetts Institute of Technology,
Evan S. Garfein of Brigham and Women's Hospital, Daniel S. Kohane of Massachusetts
General Hospital, Diane C. Darland and Patricia A. D'Amore of the Schepens
Eye Research Institute and Harvard Medical School, and Richard C. Mulligan
of Children's Hospital in Boston and Harvard Medical School.
The work appeared in the June 19, 2005 issue of Nature Biotechnology.
The research was funded by the National Institutes of Health (NIH).
TRN Categories: Biotechnology
Story Type: News
Related Elements: Technical paper, "Engineering Vascularized
Skeletal Muscle Tissue," Nature Biotechnology, June 19, 2005
June 29/July 6, 2005
Nanowire networks route
Cell combo yields
Physics maps city complexity
It Works: Self-assembly
renders ink physics
switch is electric
make nano rings
Research News Roundup
Research Watch blog
View from the High Ground Q&A
How It Works
News | Blog
Buy an ad link