Stem cell enriched-epithelial spheroid cultures for rapidly assaying small intestinal radioprotectors and radiosensitizers in vitro.

Stem cell enriched-epithelial spheroid cultures for rapidly assaying small intestinal radioprotectors and radiosensitizers in vitro.
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DOI:
10.1038/s41598-018-33747-7
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发表时间:
2018-10-18
期刊:
影响因子:
4.6
通讯作者:
Piwnica-Worms H
Piwnica-Worms H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
de la Cruz Bonilla M;Stemler KM;Taniguchi CM;Piwnica-Worms H

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放射治疗是许多癌症患者的主要治疗选择之一。虽然高剂量的辐射可以最大限度地杀死肿瘤细胞,但剂量递增受到邻近正常组织毒性的限制。这种限制尤其适用于小肠,这是体内第二大放射敏感器官。确定小肠(SI)辐射保护剂可以使剂量递增治疗腹盆腔恶性肿瘤。然而,目前可用于鉴定放射性调节药物对SI干细胞再生能力的影响的唯一测定法是Withers-Elkind微菌落测定法,其需要大量小鼠,使其成为昂贵且低通量的方法。在这里,我们描述了一种新的球体形成试验(SFA),利用SI干细胞富集的三维上皮球体文化,以确定离体胃肠放射调节剂。SFA可扩展用于高通量筛选,并可用于识别辐射防护剂和辐射增敏剂。
Radiation therapy is one of the main treatment options for many cancer patients. Although high doses of radiation may maximize tumor cell killing, dose escalation is limited by toxicity to neighboring normal tissues. This limitation applies particularly to the small intestine, the second most radiosensitive organ in the body. Identifying small intestinal (SI) radioprotectors could enable dose escalation in the treatment of abdominopelvic malignancies. However, the only assay currently available to identify effects of radiomodulating drugs on the regenerating capacity of SI stem cells is the Withers-Elkind microcolony assay, which requires large numbers of mice, making it a costly and low throughput method. Here, we describe a novel spheroid formation assay (SFA) that utilizes SI stem cell-enriched three-dimensional epithelial spheroid cultures to identify gastrointestinal radiomodulators ex vivo. The SFA is scalable for high throughput screening and can be used to identify both radioprotectors and radiosensitizers.
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