Background: therapeutic angiogenesis has recently been developed as a new method of treatment for several ischaemic diseases; both experimentally and clinically there is preliminary data suggesting that implantation of bone marrow-mononuclear cells into ischaemic limbs increases collateral vessels formation.
Aims: to evaluate viability of the therapeutic angiogenesis using hematopoyetic bone marrow progenitors mobilized by G-CSF (granulocyte colony stimulating factor) and saffety of the procedure.
Methods: 28 patients developing critical arterial limb ischaemia (candidates to amputation) were included in this study (International Working Party). 15 men and 13 women. Median age 65 years old (58 – 74). Mobilized by filgrastim (Neupogen ®) 5 μg/kg weight daily (5 days). Bone marrow harvest at 5th day. Local anaesthesia was employed in all the patients. Unmanipulated cells were injected in the affected limb in 2 ml aliquots into the gastrocnemius muscle. All the patients received injections unless in one limb. 1 patient received treatment in both. Each patient were evaluated regularly for rest pain, amount of required analgesia, healing of the ulcers, peack walking time, Doppler and angiographic findings. The mean number of injected mononuclear cells was 1,5 ×109/kg. All the patients received low molecular weight heparin (nadroparin, Fraxiparine ®) 3800 – 5600 IU anti-Xa subcutaneously, aspirin 81 mg and pentoxifiline 400 mg daily, as medical treatment after the procedure for at least 60 to 90 days. A control population of 27 vascular patients affected by critical arterial limb isquemia was considered. They don’t received angiogenic treatment, only the same medical antithrombotic schedule described.
Results: there were no secondary effects for the mobilization or injection of cells in the 28 treated patients. There were no dead patients secondary to the procedure. Moreover, in 22 patients with a median follow up of 18 months, 20 patients showed an improvement of all parameters, mainly pain at rest, peack walking time and skin trophic lesions. One patient suffered amputation of the affected extremity because obstruction of an old by-pass (3,6%). On the control population, amputation of the affected extremity was necessary in 25 of the 27 patients evaluated with medical treatment only (90,7%). The statistical differences between the two groups were highly significant in favor of the angiogenic group. They were evaluated by the chi square test and log rank test (p<0,05).
Conclusions: our preliminary data suggest that autologous bone marrow transplantation can be performed safely and appears to be a benefical therapy for selected patients with severe peripheral arterial disease.
Disclosure: No relevant conflicts of interest to declare.