Stem cell factor improves the repopulating ability of primitive hematopoietic stem cells after sublethal irradiation (and, to a lesser extent) after bone marrow transplantation in mice
Stem cell factor improves the repopulating ability of primitive hematopoietic stem cells after sublethal irradiation (and, to a lesser extent) after bone marrow transplantation in mice
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DOI：
10.1002/stem.160112
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发表时间：
1998-01-01
期刊：
影响因子：
5.2
通讯作者：
Astle, CM
中科院分区：
文献类型：
--
作者：
Gardner, RV;Oliver, P;Astle, CM
骨髓移植（BMT）和亚致死照射（XRT）对造血干细胞造成严重的长期损伤，我们在小鼠中使用竞争性再生实验来测试粒细胞-巨噬细胞集落刺激因子（GM-CSF）和干细胞因子（SCF）的能力，在临床环境中给予细胞因子，以增强XRT或BMT后骨髓恢复的能力，并保护这些模式后原始造血干细胞（PHSC）的骨髓再生能力。可耗尽资源的再生能力？多谱系祖细胞（EMP）也在这些方式后进行了测试，有或没有细胞因子，XRT或BMT后EMP和PHSC的再生能力显着降低；XRT后给予C57B6/J小鼠SCF可改善EMP和PHSC再生能力，尽管祖细胞数量（再生单位）未完全恢复到对照水平。无论是单次给药还是多次给药，XRT后GM确实保护PHSC功能免受XRT的有害影响，但这并不显著，SCF引起BMT后PHSC再生能力的增加。但这也没有显著差异，BMT后的GM几乎没有影响，在XRT之前给SCF导致PHSC功能严重受损，几乎没有观察到干细胞活性。因此，给药的时机是一个重要的考虑因素，因为在XRT之前预先给药细胞因子可能对PHSC功能极其有害。
Bone marrow transplantation (BMT) and sublethal irradiation (XRT) cause profound long-term damage to hematopoietic stem cells, We used the competitive repopulation assay in mice to test the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF), cytokines given in clinical settings to enhance marrow recovery after XRT or BMT and to protect the marrow repopulating ability of primitive hematopoietic stem cells (PHSC) after these modalities. The repopulating ability of exhaustible? multilineage progenitors (EMP) was also tested after these modalities, with or without cytokines, Repopulating abilities of EMP and PHSC were significantly reduced after XRT or BMT; PHSC were preferentially affected, Administration of SCF to C57B6/J mice after XRT resulted iaa improved EMP and PHSC repopulating ability, although progenitor numbers-repopulating units-were not completely returned to control levels, Whether given as a single dose car multiple doses, GM after XRT did protect PHSC function from the deleterious effects of XRT, but this was not a significant effect, SCF caused an increase in PHSC repopulating ability after BMT, but this too was not a significant difference, GM after BMT had little effect, SCF administration before XRT led to severe impairment of PHSC function with very little or no stem cell activity observed, Therefore, timing of its administration is an important consideration since preadministration of the cytokine before XRT can be extremely harmful to PHSC function.