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
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
1959-1975Subventions
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