Autologous transplantation of bone marrow mononuclear cells for limb ischemia in a caucasian population with atherosclerosis obliterans

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Abstract
Background. Autologous transplantation of bone marrow mononuclear cells (ATBMMNC) has been used successfully in critical limb ischemia. All reported patients were of Asian descent, however, and several studies included only young patients with thromboangiitis obliterans. Whether the beneficial results can be extrapolated to older Caucasian patients with atherosclerosis obliterans and a heavy burden of cardiovascular risk factors remains unclear. Methods. We enrolled 16 patients (age 78 ± 2 year) with critical limb ischemia and a high prevalence of hypertension, smoking, diabetes, hypercholesterolemia and uremia. Mononuclear cells were isolated from the bone marrow and injected in the gastrocnemius muscle of the affected limb. Results. Four patients died because of progressive gangrene (two) or unrelated causes (two). Three patients required an amputation and one patient a femorocrural bypass within 12 weeks. The remaining eight patients had a modest improvement of resting pain and/or trophic lesions. Transcutaneous oxygen pressure (ratio lesion/reference) improved from 0.51 ± 0.11 before to 0.86 ± 0.03 (P < 0.001) after 12 weeks, whereas ankle-brachial index did not change significantly (0.42 ± 0.15 vs. 0.59 ± 0.1; P = 0.23). The number of visible collateral vessels on digital subtraction angiography changed with 0.89 ± 0.86 on a scale of 1–4 (P = 0.33). Capillary surface area in a biopsy of gastrocnemius, evaluated by immunostaining for endothelial nitric oxide synthase, increased from 0.61 ± 0.07% to 2.38 ± 0.73% (P < 0.05). Conclusions. Although ATBMMNC was associated with objective signs of neovascularization, symptomatic improvement was only modest and restricted to the least affected patients. The discrepancy with previous findings may be related to the high prevalence of cardiovascular risk factors which causes endothelial progenitor cell dysfunction.