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使用声学生物打印的患者来源的3D肿瘤微组织模拟癌症转移。

Modeling cancer metastasis using acoustically bio-printed patient-derived 3D tumor microtissues.

作者信息

Chen Hui, Du Liang, Li Juan, Wu Zhuhao, Gong Zhiyi, Xia Yu, Fan Zhou, Qian Qun, Ding Zhao, Hu Hang, Guo Shishang

机构信息

Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.

Department of Colorectal and Anal Surgery, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan 430072, China.

出版信息

J Mater Chem B. 2022 Mar 16;10(11):1843-1852. doi: 10.1039/d1tb02789a.

Abstract

Cancer metastasis causes most cancer-related deaths, and modeling cancer invasion holds potential in drug discovery and companion diagnostics. Although 2D cocultures have been developed to study cancer invasion, it is challenging to recreate the 3D cancer invasion of an individual cancer patient. Here, we report an acoustic bioprinting technology that can precisely construct tumor microtissues for modeling cancer invasion in 3D. By using acoustic droplet technology, we can precisely encapsulate cancer associated fibroblasts (CAFs) derived from a colorectal cancer patient into gel droplets and print them into a 3D CAF microtissue. After depositing a tumor organoid derived from the same patient, our 3D bio-printed microtissue can be used to model cancer cell migration and invasion from the tumor organoid to the 3D CAF microtissue. We further used 3D bio-printed microtissues to investigate cancer invasion dynamics as well as their treatment response using time-lapse imaging. Thus, our acoustic 3D bioprinting technology can be widely used for establishing various microtissues for modeling cancer invasion and other diseases, highlighting its potential in personalized treatment.

摘要

癌症转移导致了大多数与癌症相关的死亡,而构建癌症侵袭模型在药物研发和伴随诊断方面具有潜力。尽管二维共培养技术已被用于研究癌症侵袭,但重建个体癌症患者的三维癌症侵袭情况仍具有挑战性。在此,我们报告了一种声学生物打印技术,该技术能够精确构建肿瘤微组织,用于模拟三维空间中的癌症侵袭。通过使用声滴技术,我们可以将源自一名结直肠癌患者的癌症相关成纤维细胞(CAF)精确封装到凝胶液滴中,并将其打印成三维CAF微组织。在植入源自同一名患者的肿瘤类器官后,我们的三维生物打印微组织可用于模拟癌细胞从肿瘤类器官向三维CAF微组织的迁移和侵袭。我们进一步使用三维生物打印微组织,通过延时成像来研究癌症侵袭动力学及其治疗反应。因此,我们的声学三维生物打印技术可广泛用于构建各种微组织,以模拟癌症侵袭及其他疾病,凸显了其在个性化治疗中的潜力。

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