CD133+ Pluripotent Stem Cells for the Treatment of Chronic Liver Failure

• Published in: Blood 2010-11, Vol.116 (21), p.1185-1185
• Main Authors: Catani, Lucia, Lorenzini, Stefania, Giordano, Rosaria, Caraceni, Paolo, Motta, Maria Rosa, Giudice, Valeria, Montemurro, Tiziana, Giannone, Ferdinando, Sollazzo, Daria, Dan, Elisa, Nicolini, Benedetta, Chelli, Francesca, Baccarani, Michele, Bernardi, Mauro, Losinno, Francesco, Andreone, Pietro, Lemoli, Roberto M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V116.21.1185.1185

Abstract 1185 The potential role of bone marrow (BM)-derived stem cells (SCs) in patients with end-stage liver disease has been addressed by our group in four studies. Main objectives were: 1) to assess stem/progenitor cell mobilization in 24 patients receiving orthotopic liver transplantation (OLT); 2) to evaluate whether G-CSF can be safely administered to patients with liver cirrhosis in order to expand and mobilize BM-derived SCs; 3) to investigate the effects of transplantation of human G-CSF-mobilized CD34+ and CD133+ SCs in mice with chronic liver injury and fibrosis; 4) to evaluate the feasibility and the safety of the purification and intrahepatic reinfusion of increasing numbers of autologous BM-derived G-CSF-mobilized CD133+ SCs in patients with end-stage liver disease. 1) Flow cytometry analysis, clonogenic assays and RT-PCR have been performed after OLT; 2) 18 patients with advanced liver disease were consecutively treated with increasing doses of G-CSF starting from 2 μg/kg/daily; 3) C57BL/6N mice received CCl4 by inhalation for thirteen weeks and were treated with Cyclosporin-A. Transplantation was performed by injection (tail vein) of 106 CD34+ or CD133+ SCs of three cirrhotic patients. After four weeks from transplantation all mice were sacrificed; 4) G-CSF at 7.5μg/Kg/b.i.d. is administered subcutaneosly (sc) from day 1 until the completion of peripheral blood stem cells (PBSC) collection. Collection of PBSC will begin on day + 4 only if the concentration of CD133+ cells is 38/mL. PB mononuclear cells obtained from mobilized standard-volume leukapheresis will be incubated with Macs colloidal superparamagnetic CD133 microbeads. CliniMacs device is used for the positive selection of CD133+ SCs under GMP conditions. At least 4 weeks after SC mobilization, collection and cryopreservation, highly purified autologous G-CSF-mobilized CD133+ cells are re-infused through the hepatic artery by transfemoral or transbranchial arteriography. CD133+ cells are administered to patients starting from 5×104/Kg patient's body weight and increased every 3 patients. The maximum infused cell dose will be 1×106/kg. G-CSF at 5μg/Kg/day is administered sc for 3 days after the reinfusion of SCs for their expansion and to induce a selective proliferative advantage of reinfused cells in vivo. 1) We demonstrated that both early subsets of the hematopoietic SC compartment (CD34+/CD90+ cells) and more mature committed progenitors (CFU-C) were mobilized into PB after OL