Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy.

chemotherapy immunotherapy microfluidic device pancreatic cancer patient-derived organoid

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569

Informations de publication

Date de publication:
29 Nov 2023
Historique:
revised: 17 10 2023
received: 13 05 2023
medline: 29 11 2023
pubmed: 29 11 2023
entrez: 29 11 2023
Statut: aheadofprint

Résumé

Patient-derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non-resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold-standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments.

Identifiants

pubmed: 38018486
doi: 10.1002/advs.202303088
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2303088

Subventions

Organisme : NIH HHS
ID : CA236612
Pays : United States
Organisme : NIH HHS
ID : P30DK084567
Pays : United States
Organisme : NIH HHS
ID : P50CA116201
Pays : United States
Organisme : NIH HHS
ID : T32GM008244
Pays : United States
Organisme : NIH HHS
ID : R01HL155150
Pays : United States
Organisme : NIH HHS
ID : P01CA111412
Pays : United States
Organisme : NIH HHS
ID : P01CA65493
Pays : United States
Organisme : NIH HHS
ID : R35CA197292
Pays : United States

Informations de copyright

© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

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Auteurs

Daheui Choi (D)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.

Alan M Gonzalez-Suarez (AM)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.

Mihai G Dumbrava (MG)

Division of Experimental Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
Center for Individualized Medicine, Epigenomics program, Mayo Clinic, Rochester, MN, 55905, USA.

Michael Medlyn (M)

Division of Oncology Research, College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.

Jose M de Hoyos-Vega (JM)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.

Frank Cichocki (F)

Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.

Jeffrey S Miller (JS)

Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.

Li Ding (L)

Division of Oncology Research, College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.

Mojun Zhu (M)

Division of Medical Oncology, Mayo Clinic, Rochester, MN, 55905, USA.

Gulnaz Stybayeva (G)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.

Alexandre Gaspar-Maia (A)

Division of Experimental Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
Center for Individualized Medicine, Epigenomics program, Mayo Clinic, Rochester, MN, 55905, USA.

Daniel D Billadeau (DD)

Division of Oncology Research, College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.

Wen Wee Ma (WW)

Division of Medical Oncology, Mayo Clinic, Rochester, MN, 55905, USA.

Alexander Revzin (A)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.

Classifications MeSH