[A clinical study on implantation of autologous bone marrow mononuclear cells after bone marrow stimulation for treatment of lower limb ischemia].

OBJECTIVE: To observe the clinical efficiency of the implantation of the autologous bone marrow mononuclear cells for treatment of lower limb ischemia after the bone marrow stimulation.

METHODS: From May to December 2005, 43 ischemic limbs in 35 patients (23 males, 12 females; aged 34-90 years,averaged 71.3 year) were treated. Of the 35 patients, 30 had diabetic lower limb ischemia with 38 lower ischemic limbs, 2 had atherosclerosis obliterans with 2 ischemic lower limbs, and 3 had thromboangiitis obliterans with 3 ischemic lower limbs. Five patients with 5 ischemic limbs were in stage I lower limb ischemia (intermittent claudication), 15 patients with ischemic 19 limbs were in stage II (rest pain), 9 patients with 12 ischemic limbs were in stage IIIa (ulceration), and 6 patients with 7 ischemic lower limbs in stage IIIb (gangrene); 88.4% of all the ischemic lower limbs (38/43)had a pain, 79.1% (34/ 43) had coldness, and 69.8% (30/43) had limb numbness. The bone marrow of each patient was stimulated by an injection of the recombinant human granulocyte-macrophage colony-stimulatory factor (GSF), 300 microg/d for 2-3 days. The bone marrow 130-200 ml was drawn from the iliac spine and the mononuclear cells were obtained. Each patient received implantation of the autologous bone marrow mononuclear cells by an intramuscular injection, an arterial intraluminal injection or a combined injection of the two routes.

RESULTS: The pain relief was found in 94.7% of the ischemic lower limbs, and pain improvement in 97.1% . Relieved numbness was found in 93.3%. The distance of the claudication was increased by all the ischemic limbs. An increase in the ankle/ brachial index (ABI) was found in 47.9%. The transcutaneous oxygen pressure (TcPO2) increased in 92.3%. The ulcer heal rate was 9.1% (1/11). Markedly-reduced ulcer wound was found in 27.3% (3/11). The amputation rate was 6.3% (3/48). Arterial angiography revealed that there was a new collateral vessel formation in 91.2%. Complications were as follows: fever and mild fatigue developed respectively in 1 patient after the bone marrow stimulation, but relieved by themselves. Acute but mild myocardial infarction was found in 1 patient with a slight precordial pain and elevation of myocardial enzymes 1 week after transplantation of the bone marrow mononuclear cells, but recovered after medical treatment. The follow-up averaged 5 months. According to the subjective criteria, the overall efficacy was 90%. ABI increased in 62.5% of the patients after operation and the value of TcPO2 was higher in 90% of the patients after this kind of therapy. Arterial angiography revealed a new collateral vessel formation in 90.5% of the 21 ischemic limbs. The foot ulcer healed in 7 and obviously improved in 3. Three of the foot ulcer patients were discharged 2-3 months after the amputation was performed on the diseased toes.

CONCLUSION: Implantation of the autologous bone marrow mononuclear cells after the bone marrow stimulation of treatment of the lower limb ischemia has advantages of less marrow aspiration, more mononuclear cell content, satisfactory short-term effect, and relatively high safety. It is a new method of treating the lower limb ischemia besides the autologous bone marrow and peripheral blood mononuclear cell implantation. The long-term effect of this method needs a further study.