Rapid tissue prototyping with micro-organospheres.

CAR-T SARS-COV-2 cytostatic cytotoxic deep learning demulsification drug resistant micro-organospheres organoid patient derived organoid

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
13 09 2022
Historique:
received: 22 06 2022
revised: 22 07 2022
accepted: 23 07 2022
pubmed: 20 8 2022
medline: 17 9 2022
entrez: 19 8 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35985334
pii: S2213-6711(22)00376-9
doi: 10.1016/j.stemcr.2022.07.016
pmc: PMC9481922
pii:
doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1959-1975

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM122465
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214300
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM145449
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007171
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217514
Pays : United States

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

Références

Med (N Y). 2021 Sep 10;2(9):1011-1026
pubmed: 34617071
Cancer Immunol Res. 2019 Feb;7(2):183-192
pubmed: 30651288
EMBO J. 2019 Feb 15;38(4):
pubmed: 30643021
Clin Cancer Res. 2020 Jul 15;26(14):3662-3670
pubmed: 32376656
Cell Stem Cell. 2020 Jan 2;26(1):17-26.e6
pubmed: 31761724
Adv Sci (Weinh). 2021 Nov;8(21):e2102418
pubmed: 34494727
Cell. 2018 Sep 6;174(6):1586-1598.e12
pubmed: 30100188
Biomater Sci. 2020 Oct 7;8(19):5476-5488
pubmed: 32914807
Cell. 2018 Jan 11;172(1-2):373-386.e10
pubmed: 29224780
Adv Sci (Weinh). 2020 Apr 11;7(11):1903739
pubmed: 32537414
iScience. 2020 Aug 21;23(8):101372
pubmed: 32745985
Nat Genet. 2014 Dec;46(12):1264-6
pubmed: 25344691
Cell. 2018 Dec 13;175(7):1972-1988.e16
pubmed: 30550791
Biomicrofluidics. 2017 Jul 20;11(4):044107
pubmed: 28794817
Science. 2018 Feb 23;359(6378):920-926
pubmed: 29472484
Nat Cell Biol. 2020 Mar;22(3):321-331
pubmed: 32123335
Nat Cell Biol. 2019 Aug;21(8):1041-1051
pubmed: 31371824
Cell Stem Cell. 2022 Jun 2;29(6):905-917.e6
pubmed: 35508177
Nat Biomed Eng. 2020 Sep;4(9):863-874
pubmed: 32514094
Cell Rep. 2020 May 26;31(8):107670
pubmed: 32460010
Nat Protoc. 2020 Jan;15(1):15-39
pubmed: 31853056
Gastroenterology. 2011 Nov;141(5):1762-72
pubmed: 21889923
EMBO J. 2019 Jun 17;38(12):
pubmed: 31036555
Clin Cancer Res. 2021 Aug 1;27(15):4397-4409
pubmed: 34083237
Nat Med. 2013 Nov;19(11):1389-400
pubmed: 24202392
Nat Cell Biol. 2018 Aug;20(8):909-916
pubmed: 30038251
Cancer Discov. 2019 Jul;9(7):852-871
pubmed: 31053628
Nat Protoc. 2013 May;8(5):870-91
pubmed: 23558786
J Theor Biol. 2011 Jun 21;279(1):63-73
pubmed: 21440560
J Clin Med. 2019 Nov 05;8(11):
pubmed: 31694307
Sci Transl Med. 2019 Oct 9;11(513):
pubmed: 31597751
Cell Rep Med. 2020 Dec 22;1(9):100161
pubmed: 33377132
Cell. 2015 May 7;161(4):933-45
pubmed: 25957691
Cancer Cell. 2022 Jan 10;40(1):26-35
pubmed: 34951956
Stem Cell Reports. 2021 May 11;16(5):1347-1362
pubmed: 33979603
Curr Opin Biotechnol. 2015 Dec;35:86-93
pubmed: 26051090
Nature. 2015 May 7;521(7550):43-7
pubmed: 25924068
Cancer Discov. 2018 Sep;8(9):1112-1129
pubmed: 29853643
Nat Med. 2019 Oct;25(10):1607-1614
pubmed: 31591597
Nature. 2020 Sep;585(7826):588-590
pubmed: 32698190

Auteurs

Zhaohui Wang (Z)

Woo Center for Big Data and Precision Health, Pratt School of Engineering, Duke University, Durham, NC, USA.

Matteo 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.

Rosemary 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.

Naveen Natesh (N)

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.

Elena S 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.

Carolyn Hsu (C)

College of Arts and Sciences, University of Chapel Hill, Chapel Hill, NC, USA.

Marcos Negrete (M)

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.

Haipei Yao (H)

Biology Department, Trinity School of Arts and Sciences, Duke University, Durham, NC, USA.

William Quayle (W)

Xilis, Inc., Durham, NC, USA.

Brook E Heaton (BE)

Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA.

Alfred T Harding (AT)

Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA.

Shree Bose (S)

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.

Else 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.

Joep 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.

Grecia O Rivera (GO)

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.

Ravian L van Ineveld (RL)

Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 Utrecht, the Netherlands.

Donald Gex (D)

Xilis, Inc., Durham, NC, USA.

Jessica DeVilla (J)

Xilis, Inc., Durham, NC, USA.

Daisong 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.

Jens 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.

Maarten H 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.

Athena Yeung (A)

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.

Cait Hamele (C)

Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA.

Amber Smith (A)

Xilis, Inc., Durham, NC, USA.

Eric Bankaitis (E)

Xilis, Inc., Durham, NC, USA.

Kun Xiang (K)

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.

Shengli Ding (S)

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA; Xilis, Inc., Durham, NC, USA.

Daniel Nelson (D)

Xilis, Inc., Durham, NC, USA.

Daniel Delubac (D)

Xilis, Inc., Durham, NC, USA.

Anne Rios (A)

Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 Utrecht, the Netherlands.

Ralph Abi-Hachem (R)

Department of Head and Neck Surgery and Communication Sciences, School of Medicine, Duke University, Durham, NC, USA.

David Jang (D)

Department of Head and Neck Surgery and Communication Sciences, School of Medicine, Duke University, Durham, NC, USA.

Bradley J Goldstein (BJ)

Department of Head and Neck Surgery and Communication Sciences, School of Medicine, Duke University, Durham, NC, USA.

Carolyn Glass (C)

Department of Pathology, School of Medicine, Duke University, Durham, NC, USA.

Nicholas S Heaton (NS)

Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA.

David Hsu (D)

Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC, USA. Electronic address: shiaowen.hsu@duke.edu.

Hans 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.

Xiling 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.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH