Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease: a phase I clinical trial

Background: Bone marrow stem/progenitor cells seem to be effective in liver regeneration after tissueinjury. Aim: To evaluate the feasibility and safety of the mobilization and reinfusion of CD133+stem/progenitorcells in patients with end-stage liver disease.Methods: Autologous CD133+stem/progenitor cells, mobilized with granulocyte-colony stimulating fac-tor, were collected by leukapheresis and reinfused at increasing doses through the hepatic artery startingfrom 5 × 104/kg up to 1 × 106/kg.Results: 16 subjects with Model for End-stage Liver Disease (MELD) score between 17 and 25 wereenrolled, 14 mobilized an adequate number of CD133+stem/progenitor cells and 12 were reinfused.No severe adverse events related to the procedure were reported. MELD score significantly worsenedduring mobilization in Child Turcotte Pugh-C patients. A significant improvement of liver function wasobserved 2 months after reinfusion (MELD 19.5 vs 16; P = 0.045). Overall, 5 patients underwent livertransplantation within 12 months from reinfusion and 2 died because of progressive liver failure.Conclusions: CD133+stem/progenitor cells reinfusion in patients with end-stage liver disease is feasi-ble and safe. A worsening of liver function was observed during mobilization in Child Turcotte Pugh-Cpatients. The temporary improvement of MELD score after reinfusion suggests that stem cells therapymay be a “bridge to transplant” approach for these patients.