Autologous Bone Marrow-Derived Stem Cell Therapy in Patients with Severe Peripheral Arterial Disorders: A Pilot Study.

Introduction. Amputation is the only current option for relief of rest pain or gangrene in patients with severe peripheral arterial disease (SPAD). Up to now, no effective blood-flow enhancement therapies are available. Autologous bone marrow-derived stem cell transplantation (ABMSCT) is an arising therapy modality with an option of building new blood vessels through endothelial stem and/or progenitor cells. Methods. Five patients with SPAD (4 with Buerger’s disease and 1 with arteriosclerosis obliterans) were treated by ABMSCT. CD34+/CD133+ cell counts were determined in aspirated bone marrow, CD34+ cells were isolated by magnetic separation and collected into a 10 ml sample. The stem cell suspension was administered by local intramuscular injections (0.5–1.0 ml injections in the musculus gastrocnemius). The follow-up (before; 1−, 3− and 6 months after ABMSCT) based on clinical (rest pain, walking distance without pain, changes of non-healing ulcers, ABI) and laboratory (DS-angiography, Color- and Laser-Doppler scan, TcPO₂ measurement and endothel function test) parameters was documented and analyzed. Our goal was to treat the worse limb of all the 5 patients.

Results. Therapeutic benefit was shown by complete regression of rest pain in all 5 patients, and by the significant increase of pain-free walking distance (36 m vs. 440 m). Six months after ABMSCT the ischemic ulcers disappeared in 2 patients, and in another 2 patients the large and deep ulcers became smaller and thinner (from 8 cm2 to 2.6 cm² in one case, and from 30 cm² to 8 cm² in another case), and in 1 case no change was realized, where osteomyelitis of the affected toe was diagnosed. The average of ABI improved significantly on the treated lower limb (before: 0.41, 3 and 6 months after: 0.64/0.82). ABI values of the contra-lateral legs did not change. The clinical improvement started 1 months after ABMSCT, it became more prominent after 3 months, and the best clinical results were observed after 6 months of transplantation. Confirmed by post-trial observations obtained at 9 months the clinical improvement was evaluated as stable and long lasting. Using angiography we realized improvement in 3 cases, but only in 1 case using Color-Doppler scan. Before and 6/20 weeks after transplantation the TcPO₂ changed on the foot from 18.80/16.78/23.83 mmHg, and on the calf from 36.66/31.25/45.00 mmHg. The laboratory parameters did not show improvement after 1 month, however, after 3 and 6 months improved parameters were recorded. No severe complications, adverse events were detected during the 6 months follow-up period.

Conclusions. ABMSCT with isolated CD34+ cells was proved to be safe, effective and resulted in significant and sustained improvement of clinical parameters and quality of life for patients with SPAD. Multicentric, controlled clinical trials are required to confirm these preliminary clinical results.