Specific dose-response effects of TGF-beta1 on developmentally distinct hematopoietic stem/progenitor cells from human umbilical cord blood.
BACKGROUND
Transforming Growth Factor-beta1 is known to maintain primitive human hematopoietic stem/progenitor cells in a quiescent state. However, its specific role in the control of distinct progenitor cell types needs to be further elucidated. In this study, we have investigated the dose-response effect of TGF-beta1 on progenitors ranging from primitive high proliferative potential (HPP)-Mix, -GM or -BFU-E to later BFU-E, CFU-G or CFU-M.


METHODS
A clonal semi-solid assay has been used to analyze the effects of a TGF-beta1 blocking antibody (anti-TGF-beta1) or that of active TGF-beta1 added to the medium at concentrations from 10-3000 pg/ml, on these different hematopoietic stem/progenitor cell types.


CONCLUSIONS
A preferential growth inhibitory effect on the earlier progenitors was observed when low concentrations of TGF-beta1 (10-300 pg/ml) were used. Concentrations of 10-30 pg/ml TGF-beta1 were sufficient to inhibit 90% of the primitive multipotent HPP-Mix, while 100-300 pg/ml TGF-beta1 were required to inhibit 70% of the bipotent HPP-GM and early HPP-BFU-E. TGF-beta1 did not significantly inhibit or activate the growth of later CFU-G and CFU-M, even when added at concentrations 10-100 fold higher. In contrast, a significant growth-inducing effect of very low TGF-beta1 concentrations (< or =30 pg/ml) on a subset of later BFU-E was observed and cannot be explained by a switch of early into later BFU-E. These results emphasize the polyfunctional role of TGF-beta1 in the regulation of hematopoiesis and the need for low, physiological concentrations of TGF-beta1, when studying both the stem cell compartment and more mature progenitor cell subpopulations.
Fortunel
N
N
Laboratoire de Biologie des Cellules Souches Somatiques Humaines, UPR 1983 du Centre National de la Recherche Scientifique, IFC1, 7, rue Guy Môquet, 94800 Villejuif, France.
Hatzfeld
J
J
Aoustin
L
L
Batard
P
P
Ducos
K
K
Monier
M N
MN
Charpentier
A
A
Hatzfeld
A
A
D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D003114:Colony-Forming Units Assay; D036861:Delivery, Obstetric; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D006133:Growth Substances; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1