Cell Therapy for Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 204

BMDACs to ischemic muscle, whereas HIF-1 induction in BMDACs enhances
their adhesion to vascular endothelium, leading to synergistic effects of combined
therapy on tissue perfusion.
Colony Stimulating Factors for Enhancing Peripheral
Blood Stem Cells
Treatment of PVD involves use of colony stimulating factors to stimulate the bone
marrow to release EPCs, which can form new blood vessels or repair damaged
ones. In a randomized and blinded clinical trial, patients with PVD were given an
injection of either GM-CSF (granulocyte-macrophage colony stimulating factor) or
a placebo. The level of EPCs in the blood was measured before, during and after
administration of the drug or placebo. The results showed that the GM-CSF treat-
ment increased total WBC count and the total number of circulating EPCs. Patients
who received GM-CSF therapy also experienced an improvement in the ability to
walk without pain. The placebo group experienced no improvement after therapy.
Currently, GM-CSF is approved by the FDA for several uses, including in cancer
patients to increase the number of WBC to fight infection after chemotherapy; in
healthy individuals serving as bone marrow donors to stimulate the bone marrow to
release stem cells; and in patients who have had a bone marrow transplant to
increase the number of WBCs. It is still considered experimental, however, for use
to increase the level of EPCs in patients with PVD.
In 2007, Beike Biotechnology Co announced that a team at its collaborating
hospital in Shenyang, China, completed an open study to assess clinical efficacy,
safety, and feasibility of transplantation of autologous peripheral blood stem cells
mobilized with G-CSF for patients with peripheral vascular disease of the lower
extremities (Xiaofeng et al. 2006 ). At 12 weeks, primary manifestations, including
lower limb pain and coldness, were significantly improved in 137 (90.1%) of the
patients; limb ulcers improved or healed in 46 (86.8%) of the 53 patients, while 25
of the 48 (47.9%) patients with limb gangrene remained steady or improved.
Angiography before treatment, and at 12 weeks after treatment, was performed in
ten of the patients and showed formation of new collateral vessels. No severe
adverse effects or complications specifically related to cell transplantation were
observed.
Intramuscular Autologous Bone Marrow Cells
Intramuscular autologous bone marrow cells (BMCs) have also been used for the
treatment of PVD. Because tissue ischemia is associated with an overwhelming
generation of oxygen radicals and negative effects due to perturbed shear-stress,