Scientists have shed light on a common bleeding disorder by
growing and analysing stem cells from patients' blood to discover
the cause of the disease in individual patients.
The technique may enable doctors to prescribe more effective
treatments according to the defects identified in patients'
cells.
In future, this approach could go much further: these same cells
could be grown, manipulated and applied as treatments for diseases
of the heart, blood and circulation, including heart attacks and
haemophilia.
The study focused on von Willebrand disease (vWD), which is
estimated to affect 1 in 100 people and can cause excessive,
sometimes life-threatening bleeding. vWD is caused by a deficiency
of von Willebrand factor (vWF), a blood component involved in
making blood clot. vWF is produced by endothelial cells, which line
the inside of every blood vessel in our body. Unfortunately, they
are difficult to study because taking biopsies from patients is
invasive and unpleasant.
A group led by Dr Anna Randi at the National Heart and Lung
Institute, Imperial College London, used a new approach to
investigate the disease. Dr Richard Starke, a British Heart
Foundation Intermediate Fellow and lead author of the study, took
routine blood samples from eight patients with vWD, extracted stem
cells called endothelial progenitor cells, and grew them in the lab
to yield large numbers of endothelial cells.
By testing these cells, they were able to analyse each patient's
disease in unprecedented detail. In some patients, the scientists
found new types of defect, which may enable them to recommend
improved treatments. Professor Mike Laffan, a collaborator in the
study and in charge of patients with VWD at Hammersmith Hospital in
West London, is looking to apply these findings to reduce severe
bleeding in these patients.
Dr Randi believes that endothelial progenitor cells could become
an invaluable resource for testing new drugs for vWD and other
diseases. "We will be able to test the effects of a range of
compounds in the patients' own cells, before giving the drugs to
the patients themselves," she said.
This approach could have impact far beyond vWD. Endothelial
cells derived from blood could also be isolated and reinjected into
someone recovering from a heart attack, to help them grow new blood
vessels and repair the injured heart tissue. Dr Starke says this
approach avoids the main problem with transplant therapies, in
which the immune system tries to destroy the foreign material. "The
patients would receive their own cells, so they wouldn't face the
problems of rejection," he said.
Work is well underway towards achieving this goal, but
blood-derived endothelial cells are only now being explored. "There
are already many studies where patients have been injected with
stem cells to see whether damage to the heart could be repaired,
and there are some promising results," said Dr Randi. "The door is
open to such treatments, and our studies are a step towards
identifying the right cells to use."
The group's previous research has already thrown up pointers for
potential new treatments. Aside from producing vWF to form clots,
endothelial cells are responsible for forming new blood vessels. In
their last paper, the group showed that vWF is actually needed to
build healthy blood vessels. Some patients with vWD suffer severe
bleeding from the gut because defects in vWF cause their blood
vessels to develop abnormally.
"There are drugs already being used in other diseases which
target abnormal blood vessel, that could be useful to stop bleeding
in some vWD patients," said Dr Randi. "Nobody would have thought of
using them to treat vWD, but by testing them on the patient's own
endothelial cells, in the laboratory, we can find out if these
drugs work before giving them to the patient."
Scientists are now interested in the possibility of using
endothelial cells as a treatment in themselves. For instance,
haemophilia, the hereditary bleeding disorder which affected Queen
Victoria's family, might one day be treated by taking these cells
from a patient and replacing the gene that causes the disease, then
putting them back into the patient.
The paper, Cellular and molecular basis of Von Willebrand Disease: studies on
blood outgrowth endothelial cells, is published
in Blood.