Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities

Summary

Treatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 μg/day) for 5 consecutive days. On day 5, PBSCs were collected, sorted from blood circulation of patients, and then intramuscularly injected into their ischemic lower limbs. A significant improvement of clinical manifestations including severe pain, skin temperature and ulcer, was observed, without obvious adverse effect. The patient’s limb was successfully saved. Satisfactory remission was obtained 3 months after transplantation as shown by significant improvement in anklebrachial pressure index (ABI), blood flow in personal vascular laboratory (PVL), laser Doppler blood perfusion, and the angiographic scores. Our data suggest for the first time that autologous transplantation of mobilized PBSCs provides a practical, safe, and effective method of treatment for lower limb ischemia.

Keywords

Cell transplantation - angiogenesis - ischemic limb - arteriosclerosis obliterans - mobilization of peripheral blood stem cells

• References

• 1 Boccalon H, Lehert P, Mosnier M. Assessment of the prevalence of atherosclerotic lower limb arteriopathy in France as a systolic index in a vascular risk population. J Mal Vasc 2000; 25: 38-46.
• 2 Silvestre JS, Levy BI. Angiogenesis therapy in ischemic disease. Arch Mal Coeur Vaiss 2002; 95: 189-96.
• 3 Al-Khaldi A, Al-Sabti H, Galipeau J. et al.. Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model. Ann Thorac Surg 2003; 75: 204-9.
• 4 Tateishi-Yuyama E, Matsubara H, Murohara T. et al.. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360: 427-35.
• 5 Takahashi T, Kalka C, Masuda H. et al.. Ischemia and cytokine-induced mobilization of bone marrow-derived endothelial cells for neovascularization. Nat Med 1999; 05: 434-8.
• 6 Seiler C, Pohl T, Wustmann K. et al.. Promotion of collateral growth by granulocyte colonystimulating factor-combined preparatory regimen for autologous peripheral blood stem cell transplantation in patients with coronary artery disease: a randomized, double-blind, placebocontrolled study. Circulation 2001; 104: 2012-7.
• 7 Kalka C, Masuda H, Takahashi T. et al.. Vascular endothelial growth factor (165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res 2000; 86: 1198-202.
• 8 Iba O, Matsubara H, Nozawa Y. et al.. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation 2002; 106: 2019-25.
• 9 Kawachi Y, Watanabe A, Uchida T. et al.. Acute arterial thrombosis due to platelet aggregation in a patient receiving granulocyte colony-stimulating factor. Br J Haematol 1996; 94: 413-6.
• 10 Fukumoto Y, Miyamoto T, Okamura T. et al.. Angina pectoris occurring during granulocyte colony-stimulating factor-combined preparatory regimen for autologous peripheral blood stem cell transplantation in a patient with acute myelogenous leukaemia. Br J Haematol 1997; 97: 666-8.