Rapid tissue prototyping with micro-organospheres.
Autor: | Wang Z; Woo Center for Big Data and Precision Health, Pratt School of Engineering, Duke University, Durham, NC, USA., Boretto M; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Millen R; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Natesh N; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA., Reckzeh ES; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Hsu C; College of Arts and Sciences, University of Chapel Hill, Chapel Hill, NC, USA., Negrete M; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA., Yao H; Biology Department, Trinity School of Arts and Sciences, Duke University, Durham, NC, USA., Quayle W; Xilis, Inc., Durham, NC, USA., Heaton BE; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA., Harding AT; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA., Bose S; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA., Driehuis E; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Beumer J; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Rivera GO; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA., van Ineveld RL; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 Utrecht, the Netherlands., Gex D; Xilis, Inc., Durham, NC, USA., DeVilla J; Xilis, Inc., Durham, NC, USA., Wang D; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Puschhof J; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Geurts MH; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Yeung A; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA., Hamele C; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA., Smith A; Xilis, Inc., Durham, NC, USA., Bankaitis E; Xilis, Inc., Durham, NC, USA., Xiang K; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA., Ding S; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA; Xilis, Inc., Durham, NC, USA., Nelson D; Xilis, Inc., Durham, NC, USA., Delubac D; Xilis, Inc., Durham, NC, USA., Rios A; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 Utrecht, the Netherlands., Abi-Hachem R; Department of Head and Neck Surgery and Communication Sciences, School of Medicine, Duke University, Durham, NC, USA., Jang D; Department of Head and Neck Surgery and Communication Sciences, School of Medicine, Duke University, Durham, NC, USA., Goldstein BJ; Department of Head and Neck Surgery and Communication Sciences, School of Medicine, Duke University, Durham, NC, USA., Glass C; Department of Pathology, School of Medicine, Duke University, Durham, NC, USA., Heaton NS; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA., Hsu D; Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC, USA. Electronic address: shiaowen.hsu@duke.edu., Clevers H; Oncode, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu., Shen X; Woo Center for Big Data and Precision Health, Pratt School of Engineering, Duke University, Durham, NC, USA; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA; Terasaki Institute, Los Angeles, CA, USA. Electronic address: xiling.shen@terasaki.org. |
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Jazyk: | angličtina |
Zdroj: | Stem cell reports [Stem Cell Reports] 2022 Sep 13; Vol. 17 (9), pp. 1959-1975. Date of Electronic Publication: 2022 Aug 18. |
DOI: | 10.1016/j.stemcr.2022.07.016 |
Abstrakt: | In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine. Competing Interests: Conflicts of interest X.S., D.H., and H.C. are co-founders of Xilis, Inc. X.S. left Duke and joined Terasaki Institute and Xilis on November 9, 2021. H.C. is also a member of the board of directors of Roche. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/. Z.W. recently left Duke University and joined Xilis, Inc. as a full-time employee. Patents WO2020242594, US 2021/0285054, and US 2022/006279 are related to this work. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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