在免疫缺陷斑马鱼中可视化植入的人类癌症和治疗反应
Chuan Yan1, Dalton C Brunson2, Qin Tang2
1Molecular Pathology Unit, Massachusetts General Hospital Research Institute, Charlestown, MA 02129, USA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02139, USA.
Cell
|April 30, 2019
概括
我们开发了一种光学清晰的斑马鱼模型, 通过追踪细胞循环停止和细胞亡,该模型揭示了结合疗法的疗效.
科学领域:
- 比较免疫学
- 癌症生物学
- 斑马鱼模型
背景情况:
- 对癌症药物的临床前疗效评估来说,异种移植模型至关重要.
- 在异种移植中直接单细胞表型可视化仍然具有挑战性.
研究的目的:
- 开发一个光学清晰的斑马鱼异种移植模型,用于对人类癌症进行动态单细胞可视化.
- 评估结合治疗的临床前疗效.
主要方法:
- 使用prkdc-/-;il2rga-/- 斑马鱼缺乏适应性和NK免疫细胞进行异种移植.
- 使用光转换细胞系追踪和FUCCI细胞周期报告器进行动态成像.
- 使用的组合治疗是olaparib (PARP抑制剂) 和temozolomide (破坏DNA的药物).
主要成果:
- 在37°C的温度下成功地在斑马鱼中植入各种人类癌症,从而实现单细胞可视化.
- 鉴定了人类肌肉肉瘤的迁移性和增殖性细胞状态.
- 已证实组合疗法可以在G2阶段,即亡前,阻止瘤细胞的发生.
- 展示了患者衍生异种移植的成功.
结论:
- 开发的斑马鱼模型为癌症异种移植提供了动态的单细胞分辨率.
- 联合使用olaparib和temozolomide可显示出临床前对肌肉瘤的疗效.
- 这种模式可以为各种癌症提供个性化的治疗方法.
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