Differential proliferative effects of transforming growth factor-beta on human hematopoietic progenitor cells

Transforming growth factor-beta (TGF beta) regulates cell growth and differentiation in numerous cell systems, including several hematopoietic lineages. We used in vitro cultures of highly enriched hematopoietic progenitor cells stimulated by natural and recombinant growth factors to investigate the biologic effects of TGF beta 1 and TGF beta 2 on erythroid (CFU-E and burst-forming unit (BFU)-E), granulocyte-macrophage (CFU-GM) and multilineage (i.e., granulocyte, erythroid, macrophage, and megakaryocyte; CFU-GEMM) colony-forming cells. In the absence of exogenous CSF, neither TGF beta 1 nor TGF beta 2 supported progenitor cell growth. In the presence of recombinant or natural CSF, picomolar concentrations of TGF beta 1 inhibited growth of CFU-E, BFU-E, and CFU-GEMM and enhanced growth of day 7 CFU-GM. Inhibition of CFU-E and BFU-E by human and porcine TGF beta 1 was similar, ranging from 17 to 73% over a concentration range of 0.05 to 1.0 ng/ml, and was largely independent of the type of burst-promoting activity used (rIL-3 vs cell line 5637-conditioned medium). Inhibition of CFU-GEMM ranged from 79 to 98% over a concentration range of 0.25 to 1.0 ng/ml. The inhibitory effect of TGF beta 1 was progressively lost when its addition was delayed for 40 to 120 h, suggesting a mode of action during early cell divisions. In contrast, growth of CFU-GM stimulated by plateau concentrations of human rG-CSF, rGM-CSF, and rIL-3 was enhanced up to 154 +/- 22% by human TGF beta 1. Porcine platelet-derived TGF beta 2 was essentially without effect on the progenitor populations examined. These results support the hypothesis that TGF beta may play role in the regulation of hematopoietic progenitor cell proliferation by differentially affecting individual lineages and is apparently capable of doing so in the relative absence of marrow accessory cells.