Incorporation of human iPSC-derived stromal cells creates a pancreatic cancer organoid with heterogeneous cancer-associated fibroblasts.

Humans Cancer-Associated Fibroblasts / metabolism Induced Pluripotent Stem Cells / metabolism Endothelial Cells / metabolism Cell Line, Tumor Pancreatic Neoplasms / pathology Carcinoma, Pancreatic Ductal / pathology Stromal Cells / metabolism Organoids / metabolism Tumor Microenvironment Pancreatic Neoplasms
CP: Cancer air-liquid interface culture drug resistance induced pluripotent stem cell matrix free pancreatic ductal adenocarcinoma re-proliferation tumor heterogeneity

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
28 Nov 2023
Historique:
received: 21 04 2023
revised: 27 07 2023
accepted: 25 10 2023
medline: 4 12 2023
pubmed: 13 11 2023
entrez: 13 11 2023
Statut: ppublish

Résumé

The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by the tumor microenvironment (TME). In this study, to recapitulate the PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in an air-liquid interface. FPCOs were further induced to resemble two distinct aspects of PDAC tissue. Quiescent FPCOs were drug resistant, likely because the TME consisted of abundant extracellular matrix proteins that were secreted from the various types of cancer-associated fibroblasts (CAFs) derived from hiPSCs. Proliferative FPCOs could re-proliferate after anticancer drug treatment, suggesting that this type of FPCO would be useful for studying PDAC recurrence. Thus, we generated PDAC organoids that recapitulate the heterogeneity of PDAC tissue and are a potential platform for screening anticancer drugs.

Identifiants

DOI: 10.1016/j.celrep.2023.113420 PMID: 37955987
pubmed: 37955987
pii: S2211-1247(23)01432-8
doi: 10.1016/j.celrep.2023.113420
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113420

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Kenta Takeuchi (K)

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Shunsuke Tabe (S)

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

Kenta Takahashi (K)

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Frontier Sciences, Computational Biology and Medical Science, Kashiwa, Chiba, Japan.

Kenji Aoshima (K)

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Frontier Sciences, Computational Biology and Medical Science, Kashiwa, Chiba, Japan.

Megumi Matsuo (M)

Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.

Yasuharu Ueno (Y)

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Yoichi Furukawa (Y)

Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Kiyoshi Yamaguchi (K)

Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Masayuki Ohtsuka (M)

Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

Soichiro Morinaga (S)

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

Yohei Miyagi (Y)

Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Kangawa, Japan.

Tomoyuki Yamaguchi (T)

School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

Naoki Tanimizu (N)

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Electronic address: tanimizu@g.ecc.u-tokyo.ac.jp.

Hideki Taniguchi (H)

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan; Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Electronic address: rtanigu@g.ecc.u-tokyo.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Fibroblastes associés au cancer › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Cellules stromales › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Tissus › Organoïdes › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Incorporation of human iPSC-derived stromal...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Incorporation of human iPSC-derived stromal...