Cited by 1883D Printing in Biomedical ResearchCancer Cells and MetastasisInnovative Microfluidic and Catalytic Techniques Innovation

An Automated Organoid Platform with Inter-organoid Homogeneity and Inter-patient Heterogeneity

Open access
Jiang, Shengwei, Zhao, Haoran, Zhang, Weijie, Wang, Jiaqi, Liu, Yuhong, Cao, Yuanxiong, Zheng, Honghui, Hu, Zhiwei +7 more·2020·Cell Reports Medicine

Abstract

Current organoid technologies require intensive manual manipulation and lack uniformity in organoid size and cell composition. We present here an automated organoid platform that generates uniform organoid precursors in high-throughput. This is achieved by templating from monodisperse Matrigel droplets and sequentially delivering them into wells using a synchronized microfluidic droplet printer. Each droplet encapsulates a certain number of cells (e.g., 1,500 cells), which statistically represent the heterogeneous cell population in a tumor section. The system produces >400-μm organoids within 1 week with both inter-organoid homogeneity and inter-patient heterogeneity. This enables automated organoid printing to obtain one organoid per well. The organoids recapitulate 97% gene mutations in the parental tumor and reflect the patient-to-patient variation in drug response and sensitivity, from which we obtained more than 80% accuracy among the 21 patients investigated. This organoid platform is anticipated to fulfill the personalized medicine goal of 1-week high-throughput screening for cancer patients.

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Crossref · 10.1016/j.xcrm.2020.100161

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  • Droplet microfluidics was used to aggregate murine cholangiocytes into complex organoids with liver mesenchymal cells.

    “droplet microfluidics was used to aggregate murine cholangiocytes to form complex organoids with liver mesenchymal cells74.”

    From Organoids (2022) · cites this paper as [74]

    The Results (The Automated Organoid Platform; Inter-organoid Homogeneity, pages not provided) describe droplet-based microfluidic production of organoids, including mouse liver organoids. Our copy does not identify the cells used for those liver organoids as murine cholangiocytes or say they were aggregated with liver mesenchymal cells. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Ductal cell-liver mesenchymal cell co-cultures have been shown to recapitulate part of the liver portal tract architecture.

    “Recently, ductal cell-liver mesenchymal cell co-cultures have been shown to recapitulate part of the liver portal tract architecture74.”

    From Organoids (2022) · cites this paper as [74]

    The Results sections on Inter-organoid Homogeneity and Organoid Validation by Histology and Gene Expression describe liver organoid epithelium and mixed epithelial–fibroblast cultures (page unavailable). They do not identify ductal cell–liver mesenchymal cell co-cultures or report reconstruction of portal tract architecture. Searches for those cell types and for “portal tract” found no passage addressing the claim. (LLM, conf=0.76)

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  • siVEGFR-loaded nanoparticles effectively inhibited angiogenic sprouting without affecting the viability of endothelial cells.

    “It was demonstrated that the siVEGFR‐loaded nanoparticles effectively inhibited the angiogenic sprouting without affecting the viability of endothelial cells.”

    From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [116]

    The Results section describes anticancer-drug responses in tumor organoids, and STAR★Methods describes viability assays on those organoids (page numbers unavailable). Searches for siVEGFR-loaded nanoparticles, angiogenic sprouting, and endothelial-cell viability found no passage addressing the claim in our copy. (LLM, conf=0.76)

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References 39 · Cited by 188

Authors
Jiang, S., Zhao, H., Zhang, W., Wang, J., Liu, Y., Cao, Y., Zheng, H., Hu, Z., Wang, S., Zhu, Y., Wang, W., Cui, S., Lobie, P. E., Huang, L., & Ma, S.
Affiliations
  • Tsinghua–Berkeley Shenzhen Institute (CN)
  • First Affiliated Hospital of Zhengzhou University (CN)
  • Tsinghua University (CN)
  • Peking University Shenzhen Hospital (CN)
  • Shenzhen University (CN)
  • Guangzhou Medical University Cancer Hospital (CN)
Corresponding author
  • Huang, Laiqiang
  • Ma, Shaohua
Venue
Cell Reports Medicine
Publisher
Elsevier BV
Published
2020-12
Volume
1
Issue
9
Pages
100161
ISSN
2666-3791 (ISSN-L)
OpenAlex
W3115787212
Cited by
188
References
39
Citations by year
2026: 42 · 2025: 51 · 2024: 33 · 2023: 24 · 2022: 31 · 2021: 7
FWCI
4.87
Type
journal article
Language
en
Open access
Locations
  • Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • Shenzhen Science and Technology Innovation Program
  • Development and Reform Commission of Shenzhen Municipality
  • National Natural Science Foundation of China
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Physical Sciences › Engineering › Biomedical Engineering › Innovative Microfluidic and Catalytic Techniques Innovation
Keywords
organoids, interpatient heterogeneity, tumor heterogeneity, drug response prediction, personalized medicine, anticancer drug screening
MeSH terms
Animals, Automation, Biometry, Humans, Neoplasms, Organoids, Microfluidics, Mice, High-Throughput Screening Assays, Precision Medicine, Printing, Three-Dimensional

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