University of Pittsburgh researchers
have developed a new method for regrowing blood vessels with growth factor,
which could be used to treat heart disease.
Yadong Wang, study leader and University of
Pittsburgh professor, along with co-authors Johnny Huard, Hunghao Chu and
Chien-Wen Chen, have found a minimally invasive technique for transferring
growth factor into mice via injection, which stimulates the growth of new blood
The human body has growth factors that control
activities like cell proliferation, differentiation and migration. These potent
molecules can even cause cell suicide and promote
cell growth. The problem is that the body strictly controls growth factor,
and the body will destroy "free-floating" growth factor.
But now, Wang and his team have created a method
that overcame this problem. Despite the half-life for most growth factor
(injected under the skin) being a half hour or less, researchers decided to
inject the growth factor under the skin of mice directly onto a molecule called
heparin, which bonds growth factor to its receptor on the cell's surface. As
the receptor and the growth factor bind to heparin, the activity of growth
factor is increased and stabilized.
This may have solved the problem associated with
growth factor duration, but it also caused another road block: bonding heparin
to growth factor results in a water-soluble substance, which is a problem
because a majority of the human body is made up of water.
But this issue didn't stop the University of
Pittsburgh team for long. They found a positively charged molecule, called polycation,
which possesses many positive charges to counter heparin's many negative
charges. This neutralized the heparin and brought it out of solution into a
coacervate, which is an aggregate of small oil droplets.
The team was able to successfully deliver
fibroblast growth factor-2 as a result of the conversion of heparin/growth
factor complexes into coacervates. Using only one growth factor, the
the compound under the skin of mice, which caused new blood vessels to
grow. In addition, the blood vessels were still in place over a month later.
"We had structures that resembled arterioles
-- small arteries that lead to a network of capillaries," said Wang.
The procedure is minimally invasive because the
coacervate is not very viscous, meaning that you can use a thin needle to
inject the growth factor through tissue and the damage created in small. It
could also be used through a catheter, meaning that the chest wouldn't need to
be opened up for open-heart
The idea behind this discovery is to use growth
factor to help
the heart heal itself after a heart attack without negative results, like
dilating ventricles until they become too large. The growth factor would be
injected right after the heart attack to help the heart repair itself.
"Our hope would be to reduce scarring, keep
as much of the muscle alive as possible, and induce quick blood vessel
formation to bring as many nutrients as possible in order to reestablish an
environment for muscle growth," said Wang.
The team will use a disease model next to test
this method before moving on to human clinical trials. If all goes well, the
final step will be to commercialize the treatment.
study was published in Proceedings of the National Academy of