FLT3/FLK2 LIGAND PROMOTES THE GROWTH OF MURINE STEM-CELLS AND THE EXPANSION OF COLONY-FORMING CELLS AND SPLEEN COLONY-FORMING-UNITS
FLT3/FLK2 LIGAND PROMOTES THE GROWTH OF MURINE STEM-CELLS AND THE EXPANSION OF COLONY-FORMING CELLS AND SPLEEN COLONY-FORMING-UNITS
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DOI：
10.1182/blood.v85.10.2747.bloodjournal85102747
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发表时间：
1995-05-15
期刊：
影响因子：
20.3
通讯作者：
RENNICK, D
中科院分区：
文献类型：
--
作者：
HUDAK, S;HUNTE, B;RENNICK, D
利用Thy(lo)Sca1（+）干细胞研究FLT3/FLK2配体（FL）对原始造血细胞生长的影响。观察到FL与多种因子相互作用，启动干细胞的集落形成。当干细胞在液体培养中用FL +白细胞介素(IL)-3、IL-6、粒细胞集落刺激因子（G-CSF）或干细胞因子（SCF）刺激时，能够在二级甲基纤维素培养物（CFU-c）中大量产生集落的细胞。然而，只有FL + IL-6支持辐照小鼠脾脏中能够形成集落的细胞数量增加（CFU-s）。辅助细胞缺失骨髓（Lin(-) BM）实验表明，FL单独对祖细胞缺乏显著的集落刺激活性。然而，在含有SCF、G-CSF、IL-6或IL-11的培养中，FL促进了粒细胞-巨噬细胞祖细胞（CFU-GM）的生长。在这些实验中，FL增加了CFU-GM启动集落形成（招募）的数量，以及每个集落的细胞数量（协同作用）。许多菌落肉眼可见，含有大于2 × 10(4)个粒细胞和巨噬细胞。因此，FL似乎对具有高增殖潜能的原始细胞（HPP）起着强有力的共刺激作用。FL也被观察到在Lin(-) BM的液体培养中共同刺激CFU-GM的扩增。相比之下，FL对红细胞、巨核细胞、嗜酸性粒细胞或肥大细胞谱系的祖细胞没有促进生长的作用。(C) 1995年由美国血液病学会出版。
The effect of FLT3/FLK2 ligand (FL) on the growth of primitive hematopoietic cells was investigated using Thy(lo)Sca1(+) stem cells. FL was observed to interact with a variety of factors to initiate colony formation by stem cells. When stem cells were stimulated in liquid culture with FL plus interleukin (IL)-3, IL-6, granulocyte colony-stimulating factor (G-CSF), or stem cell factor (SCF), cells capable of forming colonies in secondary methylcellulose cultures (CFU-c) were produced in high numbers. However, only FL plus IL-6 supported an increase in the number of cells capable of forming colonies in the spleens of irradiated mice (CFU-s). Experiments with accessory cell-depleted bone marrow (Lin(-) BM) showed that FL alone lacks significant colony-stimulating activity for progenitor cells. Nevertheless, FL enhanced the growth of granulocyte-macrophage progenitors (CFU-GM) in cultures containing SCF, G-CSF, IL-6, or IL-11. In these assays, FL increased the number of CFU-GM initiating colony formation (recruitment), as well as the number of cells per colony (synergy). Many of the colonies were macroscopic and contained greater than 2 x 10(4) granulocytes and macrophages. Therefore, FL appears to function as a potent costimulus for primitive cells of high proliferative potential (HPP). FL was also observed to costimulate the expansion of CFU-GM in liquid cultures of Lin(-) BM. In contrast, FL had no growth-promoting affects on progenitors committed to the erythrocyte, megakaryocyte, eosinophil, or mast cell lineages. (C) 1995 by The American Society of Hematology.