高通量自动化类器官芯片研究进展

doi:10.11958/20231474

天津医药 ›› 2024, Vol. 52 ›› Issue (1): 1-3.doi: 10.11958/20231474

• 专题研究·类器官与器官芯片（主编·陈怀永） • 下一篇

高通量自动化类器官芯片研究进展

孟繁露(), 韩益明, 修继冬, 黄建永^△()

北京大学工学院（邮编100871）

收稿日期:2023-11-04 出版日期:2024-01-15 发布日期:2024-01-18
通讯作者: ^△E-mail：jyhuang@pku.edu.cn
作者简介:孟繁露（1986），女，博士，主要从事类器官与类器官芯片研究。E-mail：fanlu_meng@pku.edu.cn
基金资助:
国家自然科学基金青年项目(12302405)

Advances in high-throughput automated organoid-on-a-chip system

MENG Fanlu(), HAN Yiming, XIU Jidong, HUANG Jianyong^△()

College of Engineering, Peking University, Beijing 100871, China

Received:2023-11-04 Published:2024-01-15 Online:2024-01-18
Contact: ^△E-mail：jyhuang@pku.edu.cn

孟繁露, 韩益明, 修继冬, 黄建永. 高通量自动化类器官芯片研究进展[J]. 天津医药, 2024, 52(1): 1-3.

MENG Fanlu, HAN Yiming, XIU Jidong, HUANG Jianyong. Advances in high-throughput automated organoid-on-a-chip system[J]. Tianjin Medical Journal, 2024, 52(1): 1-3.

摘要/Abstract

摘要：

类器官是利用干细胞的自更新和自组织能力在体外构建的三维多细胞培养物，其复现了对应器官或组织的关键结构和功能特征，为发育生物学、再生医学、疾病建模和药物开发等领域提供了理想的体外模型和研究平台。然而，传统的类器官培养体系依赖于手动操作，培养流程较为繁琐，且培养物个体差异和批次差异较大，成为限制类器官转化和应用的重要原因之一。因此，工程化类器官培养体系通过引入微流控芯片技术来提升类器官培养体系的通量和自动化程度，对于实现类器官大规模、均质化、标准化培养具有重要意义。该文综述了高通量自动化类器官芯片的研究进展，并探讨了类器官培养通量和标准化的主要限制性因素和潜在挑战。

关键词: 类器官, 高通量筛选分析, 自动化, 实验室, 微井阵列, 器官芯片

Abstract:

Organoids are in vitro three-dimensional (3D) multicellular cultures that are generated through deploying the self-renewal and self-organizing capacities of stem cells. They recapitulate key structural and functional features of corresponding organs or tissues, providing an ideal in vitro model and research platform for the study of developmental biology, regenerative medicine, disease modeling and drug development. The conventional organoid culture system mainly relies on manual operations with lengthy and complicated procedures, which generate organoid cultures of individual variations and batch differences, limiting their translational applications. Therefore, to engineer the organoid culture system by introducing microfluidic chip technology to enhance the throughput and automation level, is of great significance for achieving large-scale, homogeneous, and standardized organoid cultures. This article reviews the current research progress of high-throughput and automated organoid chips and discusses the main limitations and potential challenges for the future study.

Key words: organoids, high-throughput screening assays, automation, laboratory, microwell arrays, organoid-on-a-chip

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图/表 1

参考文献 17

[1]	HOFER M, LUTOLF M P. Engineering organoids[J]. Nat Rev Mater, 2021, 6(5):402-420. doi:10.1038/s41578-021-00279-y.
[2]	ZHAO Z, CHEN X, DOWBAJ A M, et al. Organoids[J]. Nat Rev Methods Primers, 2022, 2:94. doi:10.1038/s43586-022-00174-y.
[3]	YIN X L, MEAD B E, SAFAEE H, et al. Engineering stem cell organoids[J]. Cell Stem Cell, 2016, 18(1):25-38. doi:10.1016/j.stem.2015.12.005.
[4]	CLEVERS H, LANCASTER M, TAKEBE T. Advances in organoid technology: Hans clevers, madeline lancaster, and takanori takebe[J]. Cell Stem Cell, 2017, 6:759-762. doi:10.1016/j.stem.2017.05.014.
[5]	VAN DE WETERING M, FRANCIES H E, FRANCIS J M, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients[J]. Cell, 2015, 161(4):933-945. doi:10.1016/j.cell.2015.03.053.
[6]	VLACHOGIANNIS G, HEDAYAT S, VATSIOU A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers[J]. Science, 2018, 359(6378):920-926. doi:10.1126/science.aao2774.
[7]	SATO T, VRIES R G, SNIPPERT H J, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche[J]. Nature, 2009, 459(7244):262-265. doi:10.1038/nature07935.
[8]	SATO T, STANGE D E, FERRANTE M, et al. Long-term expansion of epithelial organoids from human colon,adenoma,adenocarcinoma,and Barrett’s epithelium[J]. Gastroenterology, 2011, 141(5):1762-1772. doi:10.1053/j.gastro.2011.07.050.
[9]	BRANDENBERG N, HOEHNEL S, KUTTLER F, et al. High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays[J]. Nat Biomed Eng, 2020, 4(9):863-874. doi:10.1038/s41551-020-0565-2.
[10]	PARK S E, GEORGESCU A, HUH D. Organoids-on-a-chip[J]. Science, 2019, 364 (6444):960-965. doi:10.1126/science.aaw7894.
[11]	FANG G, CHEN Y C, LU H X, et al. Advances in spheroids and organoids on a chip[J]. Adv Funct Mater, 2023, 33:2215043. doi:10.1002/adfm.202215043.
[12]	GRACZ A D, WILLIAMSON I A, ROCHE K C, et al. A high-throughput platform for stem cell niche co-cultures and downstream gene expression analysis[J]. Nat Cell Biol, 2015, 17(3):340-349. doi:10.1038/ncb3104.
[13]	JIANG S W, ZHAO H R, ZHANG W J, et al. An automated organoid platform with inter-organoid homogeneity and inter-patient heterogeneity[J]. Cell Rep Med, 2020, 1(9):100161. doi:10.1016/j.xcrm.2020.100161.
[14]	RENNER H, GRABOS M, BECKER K J, et al. A fully automated high-throughput workflow for 3D-based chemical screening in human midbrain organoids[J]. Elife, 2020, 9:e52904. doi:10.7554/eLife.52904.
[15]	WANG Y C, JEON H. 3D cell cultures toward quantitative high-throughput drug screening[J]. Trends Pharmacol Sci, 2022, 43(7):569-581. doi:10.1016/j.tips.2022.03.014.
[16]	SAORIN G, CALIGIURI I, RIZZOLIO F. Microfluidic organoids-on-a-chip: The future of human models[J]. Semin Cell Dev Biol, 2023, 144:41-54. doi:10.1016/j.semcdb.2022.10.001.
[17]	LOUEY A, HERNANDEZ D, PEBAY A, et al. Automation of organoid cultures:current protocols and applications[J]. SLAS Discov, 2021, 26(9):1138-1147. doi:10.1177/24725552211024547.

高通量自动化类器官芯片研究进展

Advances in high-throughput automated organoid-on-a-chip system

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