ABSTRACT
Critical limb ischemia (CLI) due to Buerger's disease is a major unmet medical need with a high incidence of morbidity. This phase II, prospective, nonrandomized, open-label, multicentric, dose-ranging study was conducted to assess the efficacy and safety of i.m. injection of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (BMMSC) in CLI due to Buerger's disease. Patients were allocated to three groups: 1 and 2 million cells/kg body weight (36 patients each) and standard of care (SOC) (18 patients). BMMSCs were administered as 40-60 injections in the calf muscle and locally, around the ulcer. Most patients were young (age range, 38-42 years) and ex-smokers, and all patients had at least one ulcer. Both the primary endpoints-reduction in rest pain (0.3 units per month [SE, 0.13]) and healing of ulcers (11% decrease in size per month [SE, 0.05])-were significantly better in the group receiving 2 million cells/kg body weight than in the SOC arm. Improvement in secondary endpoints, such as ankle brachial pressure index (0.03 [SE, 0.01] unit increase per month) and total walking distance (1.03 [SE, 0.02] times higher per month), were also significant in the group receiving 2 million cells/kg as compared with the SOC arm. Adverse events reported were remotely related or unrelated to BMMSCs. In conclusion, i.m. administration of BMMSC at a dose of 2 million cells/kg showed clinical benefit and may be the best regimen in patients with CLI due to Buerger's disease. However, further randomized controlled trials are required to confirm the most appropriate dose. Stem Cells Translational Medicine 2017;6:689-699.
Subject(s)
Bone Marrow Cells/cytology , Extremities/blood supply , Ischemia/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Thromboangiitis Obliterans/therapy , Adolescent , Adult , Animals , Cells, Cultured , Extremities/pathology , Female , Humans , Injections, Intramuscular , Ischemia/pathology , Magnetic Resonance Angiography , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cells/metabolism , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Thromboangiitis Obliterans/pathology , Transplantation, Autologous , Treatment Outcome , Young AdultABSTRACT
Popliteal artery aneurysms are the common peripheral artery aneurysm. Aneurysm due to exostosis is rare in occurrence. Here, we present a rare presentation of popliteal artery aneurysm in siblings which was managed by aneurysm excision and revascularization with interposition reversed long saphenous vein graft in one child and follow-up in the other.
