Therapeutic angiogenesis by autologous bone marrow cell implantation together with allogeneic cultured dermal substitute for intractable ulcers in critical limb ischaemia

Abstract

Therapeutic angiogenesis by autologous bone marrow cell implantation improves blood supply in patients with critical limb ischaemia. In addition, allogeneic cultured dermal substitute is effective for intractable ulcers. The present study determined the effectiveness of bone marrow cell implantation combined with allogeneic cultured dermal substitute in treating severely ischaemic ulcers. We treated eight consecutive patients with severely ischaemic ulcers using this procedure. Stromal cells aspirated from bone marrow were processed to obtain suspensions of mononuclear cells, platelets and endothelial progenitor cells and immediately injected intramuscularly into the lower leg and around the wound, on which allogeneic cultured dermal substitute was applied and changed weekly. Skin ulcers were subsequently closed by skin grafting, if necessary. Angiogenesis was confirmed by postoperative analyses such as ankle-brachial pressure index, angiography, thermography and (99m)Technetium-Tetrofosmin perfusion scintigraphy. Above- or below-knee amputation was avoided in all patients and wounds were completely closed in six of them. These results indicate that this combined therapy effectively treated ischaemic ulcers. Since the incidence of this condition might increase in the future, this therapeutic approach should play an important role in the preservation of ischaemic limbs.