Stem-cell factor in aplastic anemia: in vitro expression in bone marrow stroma and fibroblast cultures.
In vitro expression of stem-cell factor (SCF) by bone marrow (BM) cells of 30 patients with aplastic anemia (AA) has been analyzed at the mRNA and protein levels. While no deficiencies were found in SCF mRNA expression, low levels of soluble SCF protein were measured in poorly growing AA stroma cultures. The SCF protein concentration in the supernatant and the confluence of AA stroma growth were found to correlate (R = 0.70). Defective proliferation was observed in the majority (20/30) of AA stroma cultures and was paralleled by poor growth of homogeneous cultures of fibroblasts from the same marrow sample. AA stroma growth was enhanced by addition of exogenous SCF in combination with interleukin-11 (IL-11), leukemia inhibitory factor (LIF), and basic fibroblast growth factor (bFGF). Our results demonstrate that deficient growth of stroma cells results in decreased production of SCF. Therefore, SCF and other stroma-derived cytokines may be of therapeutic value in AA patients with documented defects within the BM microenvironment.
Krieger
M S
MS
Department of Research, University Hospital, Basel, Switzerland.
Nissen
C
C
Wodnar-Filipowicz
A
A
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006131:Growth Inhibitors / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D019089:Stem Cell Factor; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
D006131:Growth Inhibitors; D016298:Hematopoietic Cell Growth Factors; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012333:RNA, Messenger; D019089:Stem Cell Factor; D016222:Fibroblast Growth Factor 2