Drug response in organoids generated from frozen primary tumor tissues

Drug response in organoids generated from frozen primary tumor tissues
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DOI:
10.1038/srep18889
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发表时间:
2016-01-07
期刊:
影响因子:
4.6
通讯作者:
Skala, Melissa C.
Skala, Melissa C.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Walsh, Alex J.;Cook, Rebecca S.;Skala, Melissa C.

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在三维培养中生长的原发性肿瘤类器官为研究肿瘤进展、侵袭和药物反应提供了极好的平台。然而,类器官生成方案需要新鲜的肿瘤组织,这限制了类器官的研究和临床应用。本研究调查了来自冷冻组织的类器官的细胞形态、活力和药物反应。结果表明,活的类器官可以从快速冷冻和解冻的组织以及从在DMSO补充的培养基中缓慢冷冻的散装组织生长。虽然冷冻过程会影响细胞的基础代谢率,但光学代谢成像指数在来源于新鲜组织和冷冻组织的类器官之间存在相关性,并且可用于检测从冷冻组织生长的类器官的药物反应。缓慢的DMSO冷冻组织产生的类器官比快速冷冻组织具有更准确的药物反应,因此应通过在DMSO补充的培养基中缓慢冷冻来保存大块组织用于随后的类器官产生。
Primary tumor organoids grown in three-dimensional culture provide an excellent platform for studying tumor progression, invasion, and drug response. However, organoid generation protocols require fresh tumor tissue, which limits organoid research and clinical use. This study investigates cellular morphology, viability, and drug response of organoids derived from frozen tissues. The results demonstrate that viable organoids can be grown from flash-frozen and thawed tissue and from bulk tissues slowly frozen in DMSO supplemented media. While the freezing process affects the basal metabolic rate of the cells, the optical metabolic imaging index correlates between organoids derived from fresh and frozen tissue and can be used to detect drug response of organoids grown from frozen tissues. The slow, DMSO frozen tissue yielded organoids with more accurate drug response than the flash frozen tissues, and thus bulk tissue should be preserved for subsequent organoid generation by slow freezing in DMSO supplemented media.