Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells.
Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells.
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DOI：
10.1073/pnas.0600133103
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发表时间：
2006-03
影响因子：
11.1
通讯作者：
B. Schuller;P. Binns;K. Riley;Ling Ma;M. Hawthorne;J. Coderre
中科院分区：
文献类型：
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作者：
B. Schuller;P. Binns;K. Riley;Ling Ma;M. Hawthorne;J. Coderre
血管内皮细胞损伤在肠隐窝干细胞丢失和随后的胃肠道（GI）综合征的发展中可能发挥的作用得到解决。小鼠接受全身超热中子照射，剂量率为0.57 +/- 0.04戈伊x min（-1）。通过掺入直径为70-90 nm的脂质体中，将额外剂量从10 B中中子捕获反应释放的短程（5-9微米）颗粒选择性靶向内皮细胞，所述颗粒被限制在血液中。不同的脂质体制剂在中子照射时在血液中产生45 +/- 7或118 +/- 12 μ g/g 10 B，这导致内皮细胞中的总吸收剂量率分别为1.08 +/- 0.09或1.90 +/- 0.16戈伊x min（-1）。在3.5天后照射，肠隐窝小菌落试验表明，2- 3倍增加剂量的微血管，相对于非特异性全身中子束剂量，没有造成额外的隐窝干细胞的损失超出了由中子束单独产生。仅中子束照射后GI综合征死亡的阈值剂量为9.0 +/- 0.6戈伊。在接受中子束剂量<9.0戈伊且血液中含有硼化脂质体的组中，尽管计算的内皮细胞吸收剂量高达27.7戈伊，但没有因GI综合征而死亡。这些数据表明，内皮细胞损伤不是肠隐窝干细胞丢失和GI综合征最终发展的原因。
The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 +/- 0.04 Gy x min(-1). An additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 microm) particles released from neutron capture reactions in 10B confined to the blood by incorporation into liposomes 70-90 nm in diameter. Different liposome formulations produced 45 +/- 7 or 118 +/- 12 microg/g 10B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 +/- 0.09 or 1.90 +/- 0.16 Gy x min(-1), respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 +/- 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome.