Flt3 ligand stimulates/costimulates the growth of myeloid stem/progenitor cells.
Flt3 ligand stimulates/costimulates the growth of myeloid stem/progenitor cells.
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DOI：
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发表时间：
1995-09
影响因子：
2.6
通讯作者：
H. Broxmeyer;L. Lu;S. Cooper;L. Ruggieri;Z. Li;S. Lyman
中科院分区：
文献类型：
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作者：
H. Broxmeyer;L. Lu;S. Cooper;L. Ruggieri;Z. Li;S. Lyman
本研究评价了重组人（rhu）和鼠（rmu）flt 3配体（flt 3-L）对低密度（LD）和细胞分选的CD 34 hu脐带血（CB）和骨髓（BM）细胞以及未分离的mu BM细胞中存在的骨髓干细胞和祖细胞亚群的集落形成的影响。flt 3-L本身具有弱的集落刺激活性。它刺激LD和CD 34 huCB和BM的小分散CFU-GM型集落，但不刺激BFU-E、CFU-GEMM或HPP-CFC集落。然而，flt 3-L对集落数量和大小的加和效应大于加和效应，包括用GM-CSF或IL-3刺激的CFU-GM，有或没有Steel因子（SLF）;用G-CSF刺激的CFU-G，有或没有SLF;用CSF-1刺激的CFU-M;和用Epo刺激的BFU-E、CFU-GEMM和HPP-CFC，有或没有IL-3或SLF。Flt 3-L增强SLF单独和与其他CSF组合的作用。在LD和分选的CD 34细胞上以及在单个分选和分离的CD 34细胞/孔的水平下，相似的作用是明显的。Flt 3-L增强了由SLF和PIXY 321（GM-CSF/IL-3融合蛋白）的有效组合刺激的huCD 34（+）柱分离的CB CFU-GM的未成熟亚群的扩增。虽然flt 3-L没有增强在Epo和SLF存在下接种的CFU-GEMM的再接种能力，但它增强了具有再接种能力的这些CFU-GEMM集落的数量。Flt 3-L效应不具有种属特异性; rhu和rmu形式对huCB/BM和muBM具有活性。这些结果证明了flt 3-L在体外对骨髓干细胞/祖细胞的有效直接作用刺激/共刺激活性。
The present studies evaluated effects of recombinant human (rhu) and murine (rmu) flt3 ligand (flt3-L) on colony formation by subsets of myeloid stem and progenitor cells present in low-density (LD) and cell-sorted CD34 hu cord blood (CB) and bone marrow (BM) cells and unseparated mu BM cells. By itself, flt3-L had weak colony-stimulating activity. It stimulated small dispersed CFU-GM-type colonies, but not BFU-E, CFU-GEMM, or HPP-CFC colonies, from LD and CD34 huCB and BM. However, flt3-L had additive to greater-than-additive effects on colony number and size by CFU-GM stimulated with GM-CSF or IL-3, with or without Steel factor (SLF); by CFU-G stimulated by G-CSF with or without SLF; by CFU-M stimulated by CSF-1; and by BFU-E, CFU-GEMM, and HPP-CFC stimulated by Epo with or without IL-3 or SLF. Flt3-L enhanced the effects of SLF, alone and in combination with other CSFs. Similar effects were apparent on LD and sorted CD34 cells and also at the level of single sorted and isolated CD34 cells/well. Flt3-L enhanced expansion of immature subsets of huCD34(+)-column separated CB CFU-GM stimulated by the potent combination of SLF and PIXY321 (a GM-CSF/IL-3 fusion protein). While flt3-L did not enhance the replating capacity of CFU-GEMM plated in the presence of Epo and SLF, it enhanced numbers of these CFU-GEMM colonies with the capacity to be replated. Flt3-L effects were not species-specific; rhu and rmu forms were active on huCB/BM and muBM. These results demonstrate the potent direct-acting stimulating/costimulating activities of flt3-L in vitro on myeloid stem/progenitor cells.