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首页> 外文期刊>Cell and Tissue Research >Mensenchymal stem cells can delay radiation-induced crypt death: impact on intestinal CD44(+) fragments
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Mensenchymal stem cells can delay radiation-induced crypt death: impact on intestinal CD44(+) fragments

机译:间充质干细胞可以延迟辐射诱发的隐窝死亡:对肠道CD44(+)片段的影响

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Intestinal stem cells are primitive cells found within the intestinal epithelium that play a central role in maintaining epithelial homeostasis through self-renewal and commitment into functional epithelial cells. Several markers are available to identify intestinal stem cells, such as Lgr5, CD24 and EphB2, which can be used to sort intestinal stem cells from mammalian gut. Here, we identify and isolate intestinal stem cells from C57BL/6 mice by using a cell surface antigen, CD44. In vitro, some CD44(+) crypt cells are capable of forming "villus-crypt"aEuro"like structures (organoids). A subset strongly positive for CD44 expresses high levels of intestinal stem-cell-related genes, including Lgr5, Bmi1, Hopx, Lrig1, Ascl2, Smoc2 and Rnf43. Cells from this subset are more capable of developing into organoids in vitro, compared with the subset weakly positive for CD44. However, the organoids are sensitive to ionizing irradiation. We investigate the specific roles of mesenchymal stem cells in protecting organoids against radiation-induced crypt death. When co-cultured with mesenchymal stem cells, the crypt domains of irradiated organoids possess more proliferative cells and fewer apoptotic cells than those not co-cultured with mesenchymal stem cells. Cd44v6 continues to be expressed in the crypt domains of irradiated organoids co-cultured with mesenchymal stem cells. Our results indicate specific roles of mesenchymal stem cells in delaying radiation-induced crypt death in vitro.
机译:肠道干细胞是在肠道上皮细胞中发现的原始细胞,它们通过自我更新和进入功能性上皮细胞的维持,在维持上皮稳态方面起着核心作用。几种标记物可用于鉴定肠道干细胞,例如Lgr5,CD24和EphB2,可用于从哺乳动物肠道中分离出肠道干细胞。在这里,我们通过使用细胞表面抗原CD44从C57BL / 6小鼠中识别并分离出肠道干细胞。在体外,一些CD44(+)隐窝细胞能够形成“绒毛-隐窝” aEuro”样结构(类器官)。对CD44呈强阳性的子集表达高水平的肠道干细胞相关基因,包括Lgr5,Bmi1, Hopx,Lrig1,Ascl2,Smoc2和Rnf43:与CD44弱阳性的子集相比,该子集的细胞在体外更能发育为类器官,但类器官对电离辐射敏感,我们研究了间充质的具体作用干细胞保护类器官以防辐射诱发的隐窝死亡当与间充质干细胞共培养时,与未与间充质干细胞共培养的细胞相比,被辐照的类器官的隐窝域具有更多的增殖细胞和更少的凋亡细胞。在与间充质干细胞共培养的受辐照类器官的隐窝结构域中表达,我们的结果表明间充质干细胞在延迟辐射诱导的隐窝破坏中的特定作用体外。

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