A reappraisal of the role of insulin-like growth factor I in the regulation of human hematopoiesis.
A reappraisal of the role of insulin-like growth factor I in the regulation of human hematopoiesis.
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胰岛素样生长因子 I 在人类造血调节中的作用的重新评价。
DOI：
10.1172/jci117324
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Gewirtz,AM
中科院分区：
文献类型：
--
作者：
Ratajczak,MZ;Kuczynski,WI;Onodera,K;Moore,J;Ratajczak,J;Kregenow,DA;DeRiel,K;Gewirtz,AM
IGF-I已被报道增加造血祖细胞克隆效率。为了研究这种现象，我们研究了表达IGF-I受体（IGF-IR）的人骨髓细胞的IGF-I反应性，这是一种以前未使用的直接策略。使用免疫亲和方法分离IGF-IR+和对照CD 34+骨髓细胞。然后，将细胞克隆在含有不同量的血清和谱系适当生长因子（补充有重组人IGF-I）的甲基纤维素中。与CD 34+细胞相反，IGF-IR+细胞从不产生CFU-Blast、CFU-Mix、CFU-GM、BFU-E或CFU-E。为了证实CD 34+和IGF-IR+细胞是不同的群体，我们使用逆转录PCR检测这些细胞中的IGF-I、EpO和KIT受体mRNA。CD 34+细胞的mRNA表型为EpO（+）、KIT（+）和IGF-IR（-），而IGF-IR+细胞的mRNA表型为IGF-IR（+）、EpO（-）和KIT（-）。这些结果表明IGF-IR在正常造血祖细胞上不表达或以低水平表达。后一种可能性的功能意义进行了测试，暴露CD 34+细胞IGF-IR反义寡核苷酸。集落形成不受IGF-IR的寡脱氧核苷酸破坏，这表明，即使在低水平表达，受体的功能意义是值得怀疑的。然而，当在IGF-I存在下培养时，IGF-IR+细胞产生具有轻度BFU-E刺激作用的活性。因此，如果IGF-I在造血集落形成中起作用，则可能是IGF-IR阳性辅助细胞分泌生长因子的刺激结果。对人类白血病细胞进行的研究也得到了类似的结果。图片
IGF-I has been reported to increase hematopoietic progenitor cell cloning efficiency. To investigate this phenomenon, we studied the IGF-I responsiveness of human marrow cells expressing IGF-I receptor (IGF-IR), a direct strategy not used previously. IGF-IR+ and control CD34+ marrow cells were isolated using immunoaffinity methods. Then, the cells were cloned in methylcellulose containing variable amounts of serum- and lineage-appropriate growth factors supplemented with recombinant human IGF-I. In contrast to CD34+ cells, IGF-IR+ cells never gave rise to CFU-Blast, CFU-Mix, CFU-GM, BFU-E, or CFU-E. To substantiate the suggestion that CD34+ and IGF-IR+ cells were distinct populations, we used reverse transcription PCR to detect IGF-I, EpO, and KIT receptor mRNAs in these cells. The mRNA phenotype of CD34+ cells was EpO (+), KIT (+), and IGF-IR (-), while IGF-IR+ cells were IGF-IR (+), EpO (-), and KIT (-). These results suggested that IGF-IR is either not expressed or expressed at low levels on normal hematopoietic progenitor cells. Functional significance of the latter possibility was tested by exposing CD34+ cells to IGF-IR antisense oligodeoxynucleotides. Colony formation was unaffected by oligodeoxynucleotide disruption of IGF-IR, suggesting that, even if expressed at low level, the receptor's functional significance was doubtful. Nevertheless, when cultured in the presence of IGF-I, IGF-IR+ cells elaborated an activity with mild BFU-E stimulatory effects. Accordingly, if IGF-I plays a role in hematopoietic colony formation, it is probably and results from stimulation of IGF-IR-positive ancillary cells to secrete growth factors. Studies carried out with human leukemia cells yielded similar results.Images