STEEL FACTOR (C-KIT LIGAND) PROMOTES THE SURVIVAL OF HEMATOPOIETIC STEM PROGENITOR CELLS IN THE ABSENCE OF CELL-DIVISION

STEEL FACTOR (C-KIT LIGAND) PROMOTES THE SURVIVAL OF HEMATOPOIETIC STEM PROGENITOR CELLS IN THE ABSENCE OF CELL-DIVISION
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DOI:
10.1182/blood.v86.5.1757.bloodjournal8651757
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发表时间:
1995-09-01
期刊:
影响因子:
20.3
通讯作者:
RUSCETTI, FW
RUSCETTI, FW
中科院分区:
医学1区
文献类型:
--
作者:
KELLER, JR;ORTIZ, M;RUSCETTI, FW

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已知大多数原始造血祖细胞处于非循环静止状态。此外,正常的造血祖细胞和祖细胞系显示出它们在体外存活对生长因子的绝对依赖性,然而生长因子对祖细胞存活的作用尚未与对增殖和分化的作用分开。使用体外分析系统,我们研究了生长因子是否可以促进在细胞分裂的情况下培养的干细胞的存活。这些研究表明,钢因子(SLF)和在较小程度上,白细胞介素-3(IL-3)直接促进淘析的骨髓祖细胞(逆流离心淘析[CCE]-27)的存活,这些骨髓祖细胞富集对SLF + IL-3组合有反应的原始造血祖细胞。此外,SLF促进短期重建细胞(STRC)和长期重建细胞(LTRC)在体内具有三系重建潜力的存活。相比之下,粒细胞集落刺激因子(G-CSF)、IL-6、白血病抑制因子、IL-11、IL-1、粒细胞巨噬细胞CSF(GM-CSF)和巨噬细胞CSF(M-CSF)对这些细胞的存活没有影响。在有丝分裂抑制剂(诺考达唑或阿非迪霉素)的存在下,SLF促进了CCE-27祖细胞的存活,这些祖细胞在体外对SLF加IL-3的组合以及在体内检测到的STRC和LTRCs做出响应。综上所述,这些数据表明,SLF可以直接促进造血祖细胞在没有细胞分裂的情况下的存活。这是美国政府的工作。它的使用没有限制。
It is known that the majority of primitive hematopoietic progenitors are in a noncycling quiescent state. In addition, normal hematopoietic progenitors and progenitor cell lines show an absolute dependence on growth factors for their survival in vitro, yet the effect of growth factors on progenitor cell survival has not been separated from effects on both proliferation and differentiation. Using an in vitro assay system, we examined whether growth factors could promote the survival of stem cells in culture in the absence of cell division. These studies show that steel factor (SLF) and, to a lesser extent, interleukin-3 (IL-3) directly promoted the survival of elutriated bone marrow progenitor cells (countercurrent centrifugal elutriation [CCE]-27) that are enriched for primitive hematopoietic progenitors that respond to the combination of SLF plus IL-3. Furthermore, SLF promoted the survival of short-term reconstituting cells (STRC), and long-term reconstituting cells (LTRC) with trilineage reconstitution potential in vivo. In comparison, granulocyte colony-stimulating factor (G-CSF), IL-6, leukemia inhibitory factor, IL-11, IL-1, granulocyte macrophage CSF (GM-CSF), and macrophage CSF (M-CSF) had no effect on the survival of these cells. In the presence of mitotic inhibitors (nocodazole or aphidicolin), SLF promoted the survival of CCE-27 progenitor cells that respond to the combination of SLF plus IL-3 in vitro and STRCs and LTRCs that are detected in vivo. Taken together, these data show that SLF can directly promote the survival of hematopoietic progenitor cells in the absence of cell division. This is a US government work. There are no restrictions on its use.