COMBINATION OF INTERLEUKIN-3 AND INTERLEUKIN-6 PRESERVES STEM-CELL FUNCTION IN CULTURE AND ENHANCES RETROVIRUS-MEDIATED GENE-TRANSFER INTO HEMATOPOIETIC STEM-CELLS
COMBINATION OF INTERLEUKIN-3 AND INTERLEUKIN-6 PRESERVES STEM-CELL FUNCTION IN CULTURE AND ENHANCES RETROVIRUS-MEDIATED GENE-TRANSFER INTO HEMATOPOIETIC STEM-CELLS
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DOI：
10.1073/pnas.86.22.8897
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发表时间：
1989-11-01
影响因子：
11.1
通讯作者：
NIENHUIS, AW
中科院分区：
文献类型：
--
作者：
BODINE, DM;KARLSSON, S;NIENHUIS, AW
本文研究了几种造血生长因子对小鼠骨髓原始祖细胞[集落形成单位-脾（CFU-S）]在培养2-6天中的作用。白细胞介素3（IL-3）是CFU-S在培养物中存活所必需的，IL-3和白细胞介素6（IL-6）的组合使培养物中CFU-S的数量比单独使用IL-3获得的数量增加10倍。通过竞争性再增殖来测量干细胞功能;需要IL-3，并且IL-3和IL-6似乎协同作用以增强从这些培养物中的干细胞回收。这些数据似乎是相关的逆转录病毒介导的基因转移到干细胞和祖细胞。小鼠骨髓细胞用含有人β-CD的逆转录病毒感染。珠蛋白基因在各种生长因子的存在下。用在单独IL-3存在下感染的细胞重建的17只小鼠中只有2只显示人β-IFN-γ的长期表达。珠蛋白基因（12个月），而在IL-3和IL-6存在下用感染的细胞重建的11只小鼠中有6只。条件培养基5637膀胱癌细胞，几种造血生长因子的来源，增加CFU-S的感染频率，但没有提高干细胞感染或培养的骨髓细胞的再生潜力。含有人β-来自这些动物的珠蛋白原病毒显示能够重建次级受体，其中人β-珠蛋白原病毒在次级受体中表达。珠蛋白基因的表达。
The effects of several hematopoietic growth factors on primitive murine bone marrow progenitor cells [colony-forming unit(s)-spleen (CFU-S)] have been investigated during culture for 2-6 days. Interleukin 3 (IL-3) was required for CFU-S survival in culture, and the combination of IL-3 and interleukin 6 (IL-6) increased the number of CFU-S in culture 10-fold over the number obtained with IL-3 alone. Stem cell function was measured by competitive repopulation; IL-3 was required, and IL-3 and IL-6 appear to act synergistically to enhance stem cell recovery from these cultures. These data appear to be relevant for retroviral-mediated gene transfer into stem and progenitor cells. Murine bone marrow cells were infected with a retrovirus containing the human .beta.-globin gene in the presence of various growth factors. Only 2 of 17 mice reconstituted with cells infected in the presence of IL-3 alone showed long-term expression of the human .beta.-globin gene (12 months), as opposed to 6 of 11 mice reconstituted with cells infected in the presence of IL-3 and IL-6. Medium conditioned by 5637 bladder carcinoma cells, a source of several hematopoietic growth factors, increased the frequency of infection of CFU-S but did not enhance stem cell infection or the repopulating potential of cultured bone marrow cells. Stem cells containing the human .beta.-globin provirus from these animals were shown to be capable of reconstituting secondary recipients in which the human .beta.-globin gene was expressed.