出 处:《中国实验血液学杂志》2002年第1期6-12,共7页Journal of Experimental Hematology
基 金:中国留学基金委员会资助项目~~
摘 要:本研究探讨红细胞生成素 (EPO)和重组细胞因子 (G CSF ,SCF ,IL 3和GM CSF)对患者和健康供者动员后的外周造血祖细胞的红系爆式祖细胞 (BFU E)和粒巨噬系祖细胞 (CFU GM )的集落形成和自我更新的作用。为了更好的了解上述那一种细胞因子和如何联合对干细胞的扩增更为有效 ,采用甲基纤维素半固体培养法 ,观察在单独用EPO、G CSF的基础上 ,比较联合SCF ,IL 3和GM CSF对BFU E和CFU GM的作用。结果显示 :①在EPO +IL 3和EPO +SCF +IL 3组 ,外周血BFU E自我更新显著增加 ,而EPO +SCF组则明显增加。②患者与正常供者之间BFU E的自我更新无显著差别。③G CSF联合SCF ,IL 3和GM CSF后CFU GM集落形成显著增加。患者组仅G CSF本身可使CFU GM集落形成显著增加 ,而G CSF +SCF和GMix组CFU GM集落形成明显增加。④当G CSF联合SCF ,IL 3和GM CSF可以显著增加CFU GM的自我更新 (AUC)。GMix是CFU GM的集落形成和祖细胞扩增的较佳组合。⑤正常供者比患者有较高的AUC即自我更新 ,特别是在G CSF组比患者具有显著差异 (P=0 .0 0 6 7)。The effects of erythropoietin and recombinant cytokines (G CSF, SCF, IL 3 and GM CSF) on colony formation and self renewal by erythroid burst forming units (BFU E) and granulocyte macrophage progenitors (CFU GM) from mobilized peripheral blood progenitor cells (PBPCs) of the normal donors and patients were investigated. To better understand how combinations of the cytokines may be appropriate for stem cell manipulation, a model involving replating of individual BFU E and CFU GM colonies has been used to study the effects of cytokines on colony formation and self renewal. Based on granulocyte colony stimulating factor (G CSF) and erythropoietin(EPO) alone serve as a baseline with which to compare the effects of the combinations with stem cell factor (SCF), interleukin 3 (IL 3) or granulocyte macrophage colony stimulating factor (GM CSF). The results revealed that: ① BFU E derived from PBPCs produced a significantly great numbers of subcolonies in EPO plus IL 3 and EPO+SCF+IL 3, and a difference in EPO+SCF compared with EPO alone. ② Compared patients to normal donors the self renewal ability of BFU E was not influenced after EPO plus SCF or IL 3. ③ There was a significantly increased frequency of CFU GM in the presence of SCF, IL 3, and GM CSF used in conjunction with G CSF. Comparising the frequencies of CFU GM in patients and donors, patients′ PBPCs were more sensitive to G CSF+SCF and GMix (G CSF+SCF+IL 3+GM CSF), especially to G CSF alone than donors. ④ There was a significant increase in AUC (area under the curve of subcolony distribution) in the presence of G CSF combined with other cytokines. GMix was identified as the optimal combination of cytokines for both the expansion of CFU GM as well as the expansion of clonogenic progenitor cells. ⑤ Donors have a high AUC than patients, especially there was a significant increase AUC in G CSF alone (P= 0.0067 ).
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