Acoustic Droplet Printing Tumor Organoids for Modeling Bladder Tumor Immune Microenvironment within a Week

Acoustic Droplet Printing Tumor Organoids for Modeling Bladder Tumor Immune Microenvironment within a Week
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DOI:
10.1002/adhm.202101312
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发表时间:
2021-09-23
影响因子:
10
通讯作者:
Guo, Shishang
Guo, Shishang
中科院分区:
工程技术1区
文献类型:
--
作者:
Gong, Zhiyi;Huang, Lanxiang;Guo, Shishang

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目前的类器官模型受限于不能快速制造能够在短期内模拟免疫微环境的类器官。本文提出一种基于声滴的平台,促进肿瘤类器官的快速形成,保留原有的肿瘤免疫微环境,建立个性化的膀胱癌肿瘤免疫治疗模型。结合疏水基质,声液滴打印机可以在体外一周内产生大量均匀且高存活率的膀胱肿瘤类器官。生成的类器官包含膀胱肿瘤的所有成分,包括多种免疫因子和肿瘤细胞。通过肿瘤类器官与自体免疫细胞共培养2天,体外诱导肿瘤反应性T细胞。此外,研究还表明,这些肿瘤反应性T细胞也可以提高匹配的类器官的杀伤效率。该平台具有操作简便、重复性好、稳定性好等优点,为肿瘤个性化免疫治疗提供了可靠的途径。
Current organoid models are limited by the incapability of rapidly fabricating organoids that can mimic the immune microenvironment for a short term. Here, an acoustic droplet-based platform is presented to facilitate the rapid formation of tumor organoids, which retains the original tumor immune microenvironment and establishes a personalized bladder cancer tumor immunotherapy model. In combination with a hydrophobic substrate, the acoustic droplet printer can yield a large number of homogeneous and highly viable bladder tumor organoids in vitro within a week. The generated organoids consist of all components of bladder tumor, including diverse immune elements and tumor cells. By coculturing tumor organoids with autologous immune cells for 2 days, tumor reactive T cells are induced in vitro. Furthermore, it is also demonstrated that these tumor-reactive T cells can also enhance the killing efficiency of matched organoids. Because of the easy operation, repeatability, and stability, the proposed acoustic droplet platform will provide a reliable approach for personalized tumor immunotherapy.