Repeated local implantation of autologous peripheral blood mononuclear cells for the treatment of ischaemic digits in patients with connective tissue diseases

Abstract

Blood flow in fingers and toes is often impaired in patients with CTDs, mandating amputation in some. Our previous study showed that a single implantation of autologous bone marrow cells is as effective as peripheral blood mononuclear cells (MNCs) to restore impaired blood flow, although neither has long-lasting efficacy. In this study, autologous peripheral blood MNCs were implanted repeatedly to evaluate a better efficacy. Three patients with SSc, two with microscopic polyangiitis and one with MCTD were enrolled. All patients had severe RP, ulcers and/or necrosis in the extremities. MNCs were obtained from 400 to 1600 ml of peripheral blood and implanted into 20-80 different sites in the palms and/or soles. This procedure was repeated every 3 months up to 1 year. Humoral factors were measured by ELISAs. Visual analogue scale scores for pain, coldness and subjective satisfaction were improved after implantation in all patients. Pre-treatment ulcers in five patients were cured after repeated implantations. Angiography showed increased vasculature compared with baseline. Serum levels of VEGF increased after implantation, whereas levels of IL-1β, fibroblast growth factor and endostatin had variable results. None of the patients had any adverse reactions during a follow-up period of up to 3 years. Repeated implantation of peripheral blood MNCs was effective and safe for the treatment of recalcitrant ulcers developing in ischaemic digits and toes in patients with CTD.