Hemopoietic progenitor cells and bone marrow stromal cells in patients with autoimmune hepatitis type 1 and primary biliary cirrhosis Despina S. Kyriakou 1 , Michael G. Alexandrakis 2 , Kalliopi Zachou 3 , Freda Passam 2 , Nikolaos E. Stathakis 3,4 , Georgios N. Dalekos 3,4,5, * 1 Hematology Department, University Hospital of Larisa, University of Thessaly, PO BOX 1425, Larisa, Greece 2 Hematology Department, University of Crete, Medical School, P.O. 1352, Heraklion, Crete, Greece 3 Department of Medicine, Research Laboratory of Internal Medicine, Faculty of Health Sciences, Medical School, University of Thessaly, 22 Papakiriazi str., Larisa 412 22, Greece 4 Department of Medicine, Division of Internal Medicine, Faculty of Health Sciences, Medical School, University of Thessaly, 22 Papakiriazi str., Larisa 412 22, Greece 5 Department of Medicine, Academic Liver Unit, Faculty of Health Sciences, Medical School, University of Thessaly, 22 Papakiriazi str., Larisa 412 22, Greece Background/Aims: Autologous hematopoietic stem cell transplantation has been used in severe cases of autoimmunity. We investigated whether hemopoietic progenitor cells and/or bone marrow (BM) microenvironment are affected in autoimmune hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC). Methods: We studied 13 AIH-1 patients, 13 PBC patients, 12 cirrhotic controls (CC) and ten healthy controls (HC). Flow cytometry, expansion cultures, long-term BM cultures and clonogenic progenitor cell assays were used. Stromal cell function was assessed in long-term BM cultures recharged with normal CD34 1 cells. Results: AIH-1 had increased CD34 1 , CD34 1 /CD38 1 and CD34 1 /CD38 2 cells compared to all groups (P< 0.001). PBC had lower progenitor cells compared to controls (P< 0.005). No differences were found between CC and HC. Committed progenitor cells in non-adherent cell fraction were increased in AIH-1 (P< 0.05) but decreased in PBC compared to controls (P< 0.05). Granulocyte-macrophage colony forming units (CFU) and erythroid-burst CFU were increased in AIH-1 compared to all groups (P< 0.001). PBC had these CFUs decreased compared to controls (P< 0.005). Stromal cells failed to support normal hemopoiesis in PBC. Conclusions: We demonstrated for the first time that AIH-1 had increased hemopoietic progenitor cells and normal stromal function. In PBC, progenitor cells and BM microenvironment were defective. Further studies will determine the significance of these novel findings. q 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Keywords: Stem cell transplantation; Autoimmunity; Autoimmune liver diseases; Autoimmune hepatitis; Primary biliary cirrhosis; Hemopoietic progenitor cells; Stromal cells 1. Introduction Autoimmune hepatitis (AIH) is a chronic liver disease associated with hypergammaglobulinemia and circulating autoantibodies, which, in most cases responds to immunosuppression [1,2]. The latter is true in 85% of patients within 3-years treatment. Patients who do not reach remission within 4-years therapy are at increased risk for liver transplantation [3,4]. Primary biliary cirrhosis (PBC) is characterized by destruction of the small intrahepatic bile ducts, which leads to progressive cholestasis and ultimately to cirrhosis and hepatocellular failure. Immunosuppressive and anti- inflammatory drugs have been considered but the results are 0168-8278/$30.00 q 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/S0168-8278(03)00387-8 Journal of Hepatology 39 (2003) 679–685 www.elsevier.com/locate/jhep Received 3 October 2002; received in revised form 11 June 2003; accepted 14 July 2003 * Corresponding author. Tel.: þ 30-41-0565-251; fax: þ30-41-0565-250. E-mail address: dalekos@med.uth.gr (G.N. Dalekos).