In vitro response of normal and aplastic anemia bone marrow to mast cell growth factor and in combination with granulocyte-macrophage colony-stimulating factor and interleukin-3.
We have examined the effect of mast cell growth factor (MGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3), singly or in combination, on the growth of normal and aplastic anemia (AA) bone marrow in clonogenic assay and long-term bone marrow culture (LTBMC). MGF stimulated colony-forming unit-granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and mixed colony-forming unit (consisting of granulocyte-macrophage and erythroid elements) (CFU-GEM) colony formation from both normal and AA marrow. The three-factor combination stimulated the greatest number of colonies. Marrow from less severely affected AA patients was stimulated to produce the highest number of colonies, and a normal response was possible if progenitors were present. When added to LTBMC, MGF alone had little effect. GM-CSF and IL-3 stimulated increased numbers of progenitor cells harvested each week from normal and AA LTBMC. This resulted in normal colony numbers in some patients, the majority of whom were less severely affected than the patients who did not respond in LTBMC. The three-factor combination was additive for normal CFU-GM production. However, no further increases in AA LTBMC resulted from the addition of MGF to GM-CSF and IL-3. The partial correction in clonogenic assay with MGF in some AA patients raises the possibility of therapeutic benefit. We failed to demonstrate increased progenitor cell numbers in AA LTBMC, however. Further studies may overcome possible limitations to progenitor cell proliferation.
Gibson
F M
FM
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London, UK.
Scopes
J
J
Daly
S
S
Ball
S E
SE
Gordon-Smith
E C
EC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000473:pathology*; D001854:Bone Marrow Cells; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D007377:Interleukin-3; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor