Fortunel N, Hatzfeld J, Aoustin L, Batard P, Ducos K, Monier M N, Charpentier A, Hatzfeld A
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.
Hematol J. 2000;1(2):126-35. doi: 10.1038/sj.thj.6200021.
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 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.
已知转化生长因子-β1可使原始人类造血干/祖细胞维持在静止状态。然而，其在控制不同祖细胞类型中的具体作用尚需进一步阐明。在本研究中，我们研究了转化生长因子-β1对从原始高增殖潜能（HPP）-Mix、-GM或-BFU-E到晚期BFU-E、CFU-G或CFU-M等祖细胞的剂量反应效应。
采用克隆半固体试验分析转化生长因子-β1阻断抗体（抗转化生长因子-β1）或添加到培养基中浓度为10 - 3000 pg/ml的活性转化生长因子-β1对这些不同造血干/祖细胞类型的影响。
当使用低浓度转化生长因子-β1（10 - 300 pg/ml）时，观察到对早期祖细胞有优先生长抑制作用。10 - 30 pg/ml的转化生长因子-β1浓度足以抑制90%的原始多能HPP-Mix，而抑制70%的双能HPP-GM和早期HPP-BFU-E则需要100 - 300 pg/ml的转化生长因子-β1。即使以高10 - 100倍的浓度添加，转化生长因子-β1也未显著抑制或激活晚期CFU-G和CFU-M的生长。相反，观察到极低浓度（≤30 pg/ml）的转化生长因子-β1对一部分晚期BFU-E有显著的生长诱导作用，且不能用早期BFU-E向晚期BFU-E的转变来解释。这些结果强调了转化生长因子-β1在造血调控中的多功能作用，以及在研究干细胞区室和更成熟祖细胞亚群时需要低生理浓度的转化生长因子-β1。
