Transplantation Of Autologous Bone Marrow Mononuclear Cell For Angiogenesis

BACKGROUND:
Evidence is growing that autologous bone marrow mononuclear cells (MNC) promote angiogenesis acutely. This is the first report of long term limb salvage data.

METHODS:
Between 11/2004 and 5/2006 the ischemic leg musculature in nine non-reconstructable patients (aged 39 to 73) was injected with 2-3 X 10⁹ MNC isolated by density gradient centrifugation from one liter of Bone Marrow aspirated from the pelvis. All patients had ischemic rest pain, and all had gangrene or non-healing ulcers. Co-morbifdities included thromboangiitis oblitreans (3), scleroderma (1), and diabetes (5). All had tibial occlusive disease. MNC were injected intamuscularly (0.75 ml) every 2 cm in the ischemic limb (50-60 injections). Trans-cutaneous oxymetry (TcPO₂) was performed before and 1 month after. Adjunctive therapies included hyperbaric oxygen, the Art Assist Device, wound care, and/or risk factor modification.

RESULTS:
The MNC differential was: lymphocytes 66+17%, monocytes 22+11%, PMN 10+8%, and 395+41 X10³ platelet/µl. The total CD34⁺ cell count was 5+3 X10⁷. Angiogenesis was assessed by TcPO_2, which increased from 7+6 mmHg to 22+11 mmHg at 1 month (n=8, p= 0.017). The 2 year TcPO₂ data in 2 patients were 53 and 72 mmHg (6 and 5 mmHg at enrollment). All had subjective improvement in pain and coolness. As of 8/2007, the limb salvage data are: 33, 24, 21, 21, 18, 17 months from treatment. There was one death and 2 below knee amputations.
CONCLUSIONS:
Six of the surviving 8 patients still have their limbs (75% limb salvage). A consistent boost in TcPO₂ was seen early on, corroborating other reports in the literature. Benefit appears to be sustained over time. Since adjunctive measures were also used, this study is only a glimpse into a new therapeutic frontier for limb salvage.