A bone marrow stem
cell transplant restored circulation to injured blood vessels in
animals with pulmonary hypertension, according to a study
presented at the American Heart Association’s Scientific
“This is a novel and
exciting approach,” said Duncan Stewart, M.D., professor and
director of cardiology at the University of Toronto and head of
cardiology at St. Michael’s Hospital.
arterial hypertension (PAH) is abnormally high blood pressure in
the arteries between the heart and lungs. It's a progressive
disease that can affect the arterioles and capillaries that
supply blood to the lungs.
“PAH reduces the
heart’s ability to pump blood through the lungs and gradually
leads to heart failure," Stewart said. "Today, we can achieve
some improvement with drugs, but the treatment is palliative and
can only delay death.”
flow to the lungs with a stem cell transplant in the pulmonary
vessels may hold promise as a new treatment for PAH, Stewart
His team used
endothelial progenitor cells. Endothelial cells form a thin
lining in blood vessels, providing an interface
between the vessel and blood. This lining, called the
endothelium, regulates a host of basic processes, such as blood
clotting and blood pressure.
“Our results show
that endothelial progenitor cells from the bone marrow circulate
in the bloodstream. We can use them to form new blood vessels
or repair damaged ones,” Stewart said.
co-investigator Yidan Zhao, M.D., a research associate at the
University of Toronto and St. Michael’s Hospital, removed
vascular progenitor cells from rats’ bone marrow. The cells
were cultured for five days, then injected into the pulmonary
circulation of rats with PAH. A second group of rats with PAH
received skin fibroblasts (cells), while a third group, which
did not have PAH, were used as controls.
systolic blood pressure (the pressure when the heart contracts)
was measured 21 days later. The systolic pressure of the
untreated, normal rats was 26 millimeters of mercury (mm Hg).
Rats with PAH had a systolic pressure of 47 mm Hg. Systolic
pressure fell to 32 mm Hg in those treated with endothelial
progenitor cells, and it was relatively unchanged (45 mm Hg) in
control animals treated with skin fibroblasts.
experiments, the endothelial progenitor cells were labeled with
a fluorescent marker. An imaging technique called fluorescent
microangiography was used to look at these cells to determine if
microcirculation in the pulmonary vessels had been restored.
“The cells could
be seen engrafting into the microcirculation and forming tiny
new blood vessels,” Zhao said. “In the treated rats,
microcirculation in the lungs was restored to almost normal
levels, while severe PAH was observed in untreated animals and
those that received skin fibroblasts.”
The stem cell
group also had a reduction in thickening of the heart wall.
This indicated, that the cells were not only repairing the
smaller vessels, but there were also improvements in larger
“We found a
regenerative approach that could lead to a new clinical therapy
for this devastating disease in the quite-near future,” he said.
Co-authors are Y.
D. Zhao, M.D., Ph.D.; Y. Deng, M.D.; Q. Zhang M.D., Ph.D.; L.
Kugathasan, B.Sc. and D.W. Courtman, Ph.D.