Strife A, Lambek C, Perez A, Darzynkiewicz Z, Skierski J, Gulati S, Haley J D, ten Dijke P, Iwata K K, Clarkson B D
Memorial Sloan-Kettering Cancer Center, Laboratory of Hematopoietic Cell Kinetics, New York, New York 10021.
Cancer Res. 1991 Sep 15;51(18):4828-36.
The effects of transforming growth factor beta 3 (TGF-beta 3) on growth in semisolid cultures of enriched hematopoietic progenitors derived from normal human marrow and blood were evaluated. Conditioned media from the Mo-T cell line (MoCM) were the source of colony-stimulating factors used to optimally stimulate primitive progenitors. To assess whether a proportion of granulocyte/monocyte (GM) progenitors were prevented from cycling, all sizes of GM aggregates were evaluated from 3 to 20 days. The activity of TGF-beta 3 on the growth of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM) was similar to that observed for TGF-beta 1. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or 72 h after initiation of culture, did not significantly affect the total number of marrow GM aggregates at 3, 7, 14, and 20 days, but TGF-beta 3 (1,000 pmol/liter), added initially, reduced the total number of blood GM aggregates. This suggests that some blood GM progenitors might be blocked from cycling but that the great majority of marrow GM progenitors are not blocked. Whether TGF-beta 3 (10, 100, and 1,000 pmol/liter) was added initially or after 72 h of stimulation by MoCM, there was a dose-dependent reduction of marrow and blood GM colony size even when the total number of colonies was unaffected. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or at 72 h, reduced in a dose-dependent manner the size of marrow and blood-derived BFU-E. TGF-beta 3 (1,000 pmol/liter) was more likely to reduce the total number of marrow and blood BFU-E, and this increased sensitivity of the erythroid lineage may prevent the development of this population in colonies derived from multipotential colony-forming unit-granulocyte/erythroid/monocyte (CFU-GEM). The results suggest that the main effect of TGF-beta 3 and TGF-beta 1 is to slow the rate of proliferation of hematopoietic progenitors rather than to prevent them from beginning proliferation. This results in a reduction in colony size which prevents the identification of primitive versus mature progenitor on the basis of standard criteria of colony size.
评估了转化生长因子β3（TGF-β3）对源自正常人骨髓和血液的富集造血祖细胞半固体培养物中生长的影响。Mo-T细胞系的条件培养基（MoCM）是用于最佳刺激原始祖细胞的集落刺激因子的来源。为了评估是否有一部分粒细胞/单核细胞（GM）祖细胞被阻止进入细胞周期，在3至20天内对所有大小的GM聚集体进行了评估。TGF-β3对红系爆式集落形成单位（BFU-E）和粒细胞-巨噬细胞集落形成单位（CFU-GM）生长的活性与TGF-β1观察到的相似。最初或培养开始72小时后添加的TGF-β3（10、100和1000 pmol/升），在第3、7、14和20天时对骨髓GM聚集体的总数没有显著影响，但最初添加的TGF-β3（1000 pmol/升）减少了血液GM聚集体的总数。这表明一些血液GM祖细胞可能被阻止进入细胞周期，但绝大多数骨髓GM祖细胞没有被阻止。无论最初还是在MoCM刺激72小时后添加TGF-β3（10、100和1000 pmol/升），即使集落总数不受影响，骨髓和血液GM集落大小也会呈剂量依赖性减小。最初或在72小时时添加的TGF-β3（10、100和1000 pmol/升）以剂量依赖性方式减小了骨髓和血液来源的BFU-E的大小。TGF-β3（1000 pmol/升）更有可能减少骨髓和血液BFU-E的总数，红系谱系的这种增加的敏感性可能会阻止该群体在源自多能集落形成单位-粒细胞/红系/单核细胞（CFU-GEM）的集落中的发育。结果表明，TGF-β3和TGF-β1的主要作用是减缓造血祖细胞增殖速率，而不是阻止它们开始增殖。这导致集落大小减小，从而无法根据集落大小的标准标准区分原始祖细胞和成熟祖细胞。
