Specific dose-response effects of TGF-beta1 on developmentally distinct hematopoietic stem/progenitor cells from human umbilical cord blood

The Hematology Journal : the Official Journal of the European Haematology Association
Nicolas Olivier FortunelAntoinette Hatzfeld

Abstract

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. 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. 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 ve...Continue Reading

Citations

Feb 27, 2013·The Journal of Experimental Medicine·Fabienne BrenetJoseph M Scandura
May 25, 2004·Oncogene·Katsuya ShigesadaP Paul Liu
May 15, 2015·Systems and Synthetic Biology·Anuradha Vaidya, Vaijayanti P Kale
Jun 17, 2016·Molecular & Cellular Oncology·Fabienne Brenet, Joseph M Scandura
Apr 9, 2013·Journal of Tissue Engineering and Regenerative Medicine·Pedro Z AndradeCláudia L da Silva

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