Stem-cell therapy for peripheral arterial occlusive disease.

Abstract

The aims of our study were to confirm the effectiveness via animal study and safety through clinical trials of using human cord blood-mononuclear cells (HCB-MNCs). We performed a dose-response animal study (HCB-MNCs: 4 × 10⁶, 4 × 10⁷ and 4 × 10⁸) using a limb ischaemia model in dogs to assess angiogenic responses. Safety assessment in humans in terms of graft-versus-host-disease was also done by observing an uncontrolled case series. Twelve animal ischaemic limbs and seven patients with thromboangiitis obliterans were treated with HCB-MNCs. These cells (4 × 10⁸) were injected into the ischaemic limb muscle of patients. The results were analysed at 8 weeks for the animal study and at 6 months for patients. In the animal ischaemic models, the number of capillaries, angiogenic gene expression and the angiogenic factors were increased after HCB-MNC injection. In the clinical study, the seven patients experienced no graft-versus-host-disease or cardiac/cerebral complications during the follow-up period. This preliminary study suggests that HCB-MNC might be a safe source of stem cells for treating ischaemic limbs. However, further clinical studies are needed to establish the long-term safety and the clinical efficacy of HCB-MNC transplantation in patients with ischaemic limbs.