Determining the optimal stem cell type for treatment of patients with critical ischemia

Aim. At present it is not known which cell type is best for inducing therapeutic angiogenesis in end-stage critical limb ischemia (CLI). We hypothesized that mononuclear cells mobilized with granulocyte colony stimulating factor (G-CSF) into peripheral blood are as effective as highly selective and purified CD133(+) and CD34(+) endothelial progenitor cells (EPCs). This would have significant clinical implications with regard to study designs and costs of stem cell treatment regimens. Methods. Patients with critical ischemia of lower extremity donated peripheral blood stem cells after five days of stimulation with G-CSF. Five patients in each group were either treated with CD 34, CD 133 or mononuclear cells after G-CSF stimulation. We analyzed expression of cell surface markers CD34, VEGFR-2, CD133, CD31 und CD144. Results. There were no differences in pain, ABI, ulcer healing or amputation rate between the three groups. Overall limb salvage rate was 12/15. Ony in 4/15 patients after a mean follow-up of 11 months control MRA examinations showed stem cell induced neoangiogenesis. In two patients after CD 34 cell injections in one cases after CD 133 treatment and in one case after treatment with mononuclear cells. In the remaining cases MRA analysis did not show any traces of neoangiogenesis. Injection of purified CD133(+) or CD34(+) EPCs does not yield better results than unselected mononuclear cells after G-CSF stimulation. Paracrine factors produced by the mononuclear fraction of mobilized peripheral blood may contribute more to the amelioration of critical limb ischemia than one particular cell type. Conclusion. In conclusion stem cell therapy will play an increasingly important role in the near future. Most patients can be treated with unselected cells which further reduces costs of cell based therapy.