November 18, 2002
IL (AHA) – Bone marrow cells implanted
into blood-starved (ischemic) legs formed new blood vessels,
increased blood flow and prevented amputation in people with
peripheral artery disease, researchers reported at the American
Heart Association’s Scientific Sessions 2002.
"This is the
first multicenter and double-blind clinical study to prove the
clinical efficacy of growing new blood vessels (angiogenesis)
using bone marrow cell transplantation," says the study's lead
author Hiroya Masaki M.D., Ph.D. He hopes that transplanting
bone marrow cells will establish a new therapy for peripheral
artery disease (PAD).
PAD is a
condition similar to coronary artery disease in which fatty
deposits build up along artery walls and reduce blood
circulation, mainly in arteries leading to the legs and feet. In
its early stages, a common symptom is cramping or fatigue in the
legs and buttocks during activity. PAD causes severe pain,
ulcers and sores. In its later stages, it can lead to gangrene
or a dangerous lack of blood flow, called critical limb
ischemia, which can be treated by revascularization (such as
angioplasty) or amputation.
Bone marrow cells
are promising for this type of therapy because they have the
natural ability to supply endothelial progenitor cells, says
Masaki, an associate professor in the department of laboratory
medicine and clinical sciences at Kansai Medical University in
Osaka, Japan. Endothelial progenitor cells can develop into
endothelial cells, which, in turn, can form new blood vessels.
randomly implanted either a person's own bone marrow mononuclear
cells or saline (a placebo) into the calf muscles of 45 PAD
patients. Twenty patients had bilateral ischemia (both legs) and
25 had unilateral ischemia (one leg). There was a "striking"
increase in new capillary formation in the legs of patients who
received bone marrow mononuclear cell transplants. Patients
injected with saline showed much smaller increases in collateral
that CD34-cells, which can develop into endothelial progenitor
cells, expressed basic fibroblast growth factor, vascular
endothelial growth factor and angiopoietin-1. These vascular
growth factors play key roles in angiogenesis.
progenitor cells have vascular growth factors inside the cells,"
Masaki says. "This is very advantageous for angiogenesis. By
implanting the bone marrow mononuclear cells, we deliver
endothelial progenitor cells and vascular growth factors at the
In limbs that
received the bone marrow cells, researchers noted an increase in
ankle-brachial pressure index (ABI) in 31 of 45 patients.
Baseline ABI was 0.35. Four weeks after implantation it was
0.42, and at 24 weeks it was 0.46. The ankle-brachial index test
measures blood pressure at the ankle and in the arm and divides
the two to help predict the severity of PAD. A normal resting
ABI is 0.30 – 0.91. Patients with leg pain typically have ABI
indexes ranging from 0.41 – 0.90, and those with critical leg
ischemia have indexes of 0.4 or less.
noted newly visible collateral vessels in 27 limbs. Pain
occurring at rest in the ischemic limbs diminished significantly
in 39 of 45 patients, and the amount of time they could walk on
a treadmill without pain was significantly improved (from 1.3
minutes at baseline to 3.6 at week four and 3.7 at week 24).
Participants' ischemic ulcers or gangrenes were healed in 21 of
Masaki says, the
study's findings can be applied to today's patients. However, he
warns that more research is needed to prove the treatment's
long-term efficacy and safety. "This new angiogenesis therapy
using bone marrow cell transplantation may help many patients
suffering with ischemic limbs," he says.
Eriko Tateishi-Yuyama, M.D.; Hiroaki Matsubara, M.D., Ph.D.;
Toyoaki Murohra, M.D., Ph.D.; Satoshi Shintani, M.D., Ph.D.;
Katsuya Amano, M.D.; Uichi Ikeda, M.D., Ph.D.; Kazuyuki Shimada,
M.D., Ph.D.; Hakuo Takahashi, M.D., Ph.D.; Toshiji Iwasaka,
M.D.; and Tsutomu Imaizumi, M.D., Ph.D.