Hemopoietic progenitor cells and bone marrow stromal cells in patients with autoimmune hepatitis type 1 and primary biliary cirrhosis

J Hepatol. 2003 Nov;39(5):679-85. doi: 10.1016/s0168-8278(03)00387-8.

Abstract

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+ cells.

Results: AIH-1 had increased CD34+, CD34+/CD38+ and CD34+/CD38- 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.

MeSH terms

  • ADP-ribosyl Cyclase / analysis
  • ADP-ribosyl Cyclase 1
  • Adult
  • Aged
  • Antigens, CD / analysis
  • Antigens, CD34 / analysis
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology*
  • Case-Control Studies
  • Cell Adhesion
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Flow Cytometry
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / pathology*
  • Hepatitis, Autoimmune / immunology
  • Hepatitis, Autoimmune / pathology*
  • Hepatitis, Autoimmune / physiopathology
  • Humans
  • Liver Cirrhosis, Biliary / immunology
  • Liver Cirrhosis, Biliary / pathology*
  • Liver Cirrhosis, Biliary / physiopathology
  • Membrane Glycoproteins
  • Middle Aged
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*

Substances

  • Antigens, CD
  • Antigens, CD34
  • Membrane Glycoproteins
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1