In vitro studies of bone marrow stem-cell function in uraemic children

Anaemia is a frequent symptom in children with chronic uraemia. There is only limited information about committed haemopoietic stem-cell function in renal insufficiency. The ability of bone-marrow cells to form erythropoietic and granulopoietic cell colonies in vitro was therefore tested in 13 children with chronic renal insufficiency.Following separation of mononuclear cells from bone-marrow aspirates by Ficoll-Isopaque gradient centrifugation, erythropoietic precursor cells were stimulated in plasma clots by erythropoietin. Granulopoietic precursor cells were stimulated in soft-agar gel using feeder layers of normal human leukocytes. The colonies were identified by staining and counted.The number and proliferative capacity of erythropoietic precursor cells (CFU-E) did not seem to be significantly suppressed. Under in vitro conditions, the responsiveness of CFU-E to erythropoietin seemed to be normal.Addition of autologous serum resulted in different degrees of inhibition of erythroid colony formation. The inhibitory effect of the sera was also obvious when uraemic sera were added to bone-marrow cells from subjects without renal disease. Preliminary data indicate that haemodialysis is effective in reducing this inhibitory activity which may be an important factor in the pathogenesis of anaemia in chronic renal insufficiency. The numbers and proliferative capacity of granulopoietic precursor cells (CFU-C) were normal in all the children tested.