Abstract 4534: Beneficial Effects of Autologous Bone Marrow Cell Infusion in Patients with Chronic Critical Limb Ischemia

Abstract

Short-term (within 6 weeks follow up) clinical studies indicate that implantation of bone marrow cells (BMCs) into ischemic limbs may improve peripheral ischemia. Here, the long-term safety and feasibility of intrarterial autologous BMCs with oral treatment with antioxidants and L-arginine was investigated in patients with critical ischemia due to advanced atherosclerotic peripheral arterial disease (PAD). The investigation was conformed with the Declaration of Helsinki. We obtained written informed consent from all patients and the Medical Ethics Committee of II University of Naples School of Medicine approved the protocol (March 2005). Moreover, we notified this study to the Italian Ministery of Health and to the NIH-controlled trial register ( NCT00306085 ). 18 patients with PAD (advanced III/IV Fontaine stages) were enrolled in this study. An additional group of 18 patients taking maximal drug therapy that refused BMC therapy served as control. The BMC-treated group received two doses of BMCs in the leg arteries (time 0 and 45 days). After 30 days from the first BMC dose, patients received daily antioxidants, and L-arginine. Therapeutic neoangiogenesis was estimated by angiography and laser Doppler\capillaroscopy. Ankle brachial index improvement (ΔABI: >0.1) was seen in 10 patients at 3 months and in 12 patients at 12–18 months. Ischemic ulcers improved in 13 patients (after 6 –12 months). Although 2 underwent amputation, the mean maximum walking distance significantly increased at 3 months and was sustained up to 18 months. Among conservative patients, 10 underwent amputation in comparison to 2 BMC-treated patients. Despite some small published studies employing BMC with a short follow up in PAD patients, we provide the first evidence of long-term safety and feasibility of intrarterial autologous BMC infusion and cotreatment with antioxidants and L-arginine in patients with advanced atherosclerotic PAD. Patients received both BMCs and metabolic treatment to maximize the effect of vitamin E and L-arginine. Results showed significant improvements in the ABI, ulcer healing, maximum walking distance, microcirculation blood flow, and reduction of amputation risk, without any serious adverse reactions until 18 months.