Objectives: For patients with severe, chronic limb ischemia in many cases interventional or surgical treatment is not possible anymore. In the past, both intramuscular and intraarterial transplantation of autologous BMCs had been proved therapeutically beneficial. The TAM-PAD study is the first one to analyze combined intraarterial and intramuscular BMC transplantation in its acute and long-term effects.
Methods: 13 patients with chronically ischemic limbs due to peripheral arterial disease (Fontaine stage IIb) were recruited and underwent follow-up examinations after 2 and 13 months. Mononuclear cells from bone marrow were injected intramuscular and intraarterial into the ischemic limb.
Results: In contrast to the control group, after 2 months the pain-free walking distance of the transplanted patients significantly increased (from 147 +/- 90 to 500 +/- 614 m, p = 0.001). Furthermore the ankle-brachial index was significantly improved (at rest from 0.66+/-0.18 to 0.80+/-0.15, p = 0.003, after stress from 0.64 +/- 0.19 to 0.76 +/- 0.16, p = 0.006). Similar improvement was documented in capillary-venous oxygen-saturation (thigh from 59 +/- 9 to 66 +/- 5, p = 0.005, lower leg from 56 +/- 14 to 63 +/- 5, p = 0.021) and venous occlusion plethysmography (rest from 2.1 +/- 0.7 to 2.5 +/- 0.7, p = 0.009, mean reactive hyperemia from 5.3 +/- 1.8 to 7.2 +/- 1.8, p = 0.003, and peak flow from 7.2 +/- 3.2 to 10.8 +/- 2.8, p = 0.002). After 13 months these positive effects persisted at their improved level. No side effects or complications were monitored.
Conclusions: Combined intraarterial and intramuscular transplantation of autologous mononuclear bone marrow stem cells is a clinically feasible and minimally invasive therapeutic option for patients with severe chronic peripheral occlusive arterial disease.