Additive effects of steel factor and antisense TGF-beta 1 oligodeoxynucleotide on CD34+ hematopoietic progenitor cells.
We previously demonstrated that TGF-beta 1 antisense oligodeoxynucleotides can release early CD34+ bone marrow progenitors from quiescence, and increase the numbers of mixed and large erythroid colonies. As Steel Factor (SF) has a similar effect on colony formation by CD34+ cells, we tested whether this factor acts by blocking the inhibitory effects of TGF-beta. That this is not generally the case was demonstrated by the finding that the combination of TGF-beta 1 antisense with SF in cultures of CD34+ bone marrow cells yielded enhanced colony formation that was more than additive when compared to cultures containing the single agents. This combination also yielded enhanced colony formation by CD34+ umbilical cord blood cells, but in this case, the effect was slightly less than additive. Thus in cord blood, some, but not all, of the progenitors that are maintained in quiescence by TGF-beta can be triggered into cycle by SF. However, the absolute number of CFU-GEMMs found in the antisense TGF-beta plus SF cultures of cord blood was 4-fold higher than that found in comparable bone marrow cultures. These data correlate well with our previous observations that umbilical cord blood contains 4-fold more CD34+ CD38- cells, the population found to respond to TGF-beta 1 antisense oligodeoxynucleotides.
Li
M L
ML
Centre National de la Recherche Scientifique, UPR 272, Villejuif, France.
Cardoso
A A
AA
Sansilvestri
P
P
Hatzfeld
A
A
Brown
E L
EL
Sookdeo
H
H
Levesque
J P
JP
Clark
S C
SC
Hatzfeld
J
J
D015703:Antigens, CD; D018952:Antigens, CD34; D004357:Drug Synergism; D005312:Fetal Blood / Q000166:cytology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015703:Antigens, CD; D018952:Antigens, CD34; D016298:Hematopoietic Cell Growth Factors; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases