Bone marrow stem cells and stromal cells in autoimmune cytopenias.
High-dose immunosuppression followed by autologous haemopoietic stem cell transplantation (ASCT) is a promising practice for the treatment of severe, resistant autoimmune disorders. Patients with refractory autoimmune cytopenias (AIC), primary or secondary to systemic autoimmune diseases (AID) including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), have been proposed as potential candidates for such a therapeutic procedure. An abnormal immune milieu, however, may affect the number and functional characteristics of stem cells and/or stromal cells in the bone marrow (BM) and might impact on harvesting and engraftment potential of stem cells or on BM reconstitution following engraftment in patients with AIC undergoing ASCT. Using flow cytometry and in vitro culture assays we have shown that patients with primary AIC display increased number of BM CD34+ cells in response to abnormally high production of granulocyte-colony stimulating factor (G-CSF) by BM stroma. In contrast, patients with AIC secondary to systemic AID display increased apoptosis of BM progenitor cells resulting in low CD34+ cell numbers and abnormal haemopoiesis supporting capacity of BM stroma due to the aberrant, local or systemic, inhibitory cytokine production or to intricate interactions between haemopoietic and immune cells present within the BM microenvironment. In this review we summarize the available knowledge on BM stem cell reserve and function and stromal cell function in patients with primary and secondary AIC with special reference to SLE and RA. The underlying mechanisms possibly involved in the pathogenesis of the observed abnormalities are also discussed.
Papadaki
Helen A
HA
Department of Haematology, University of Crete School of Medicine, University Hospital of Heraklion, Greece. epapadak@med.uoc.gr
Marsh
Judith C W
JC
Eliopoulos
George D
GD
D018952:Antigens, CD34 / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D001854:Bone Marrow Cells / Q000502:physiology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D017154:Stromal Cells / Q000502:physiology*
D018952:Antigens, CD34