Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids

Organoid technology, a novel 3D cell culture system, can reproduce a patient’s cancer and may be a novel immunotherapy experimental model. However, currently no gastric cancer organoid (GCO) models in which the organoid and immune cells are in free contact and sufficiently react with each other exis...

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Main Authors: Hiroshi Ota, Kazuaki Tanabe, Yoshihiro Saeki, Yuki Takemoto, Emi Chikuie, Naoya Sakamoto, Hideki Ohdan
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023107286
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author Hiroshi Ota
Kazuaki Tanabe
Yoshihiro Saeki
Yuki Takemoto
Emi Chikuie
Naoya Sakamoto
Hideki Ohdan
author_facet Hiroshi Ota
Kazuaki Tanabe
Yoshihiro Saeki
Yuki Takemoto
Emi Chikuie
Naoya Sakamoto
Hideki Ohdan
author_sort Hiroshi Ota
collection DOAJ
description Organoid technology, a novel 3D cell culture system, can reproduce a patient’s cancer and may be a novel immunotherapy experimental model. However, currently no gastric cancer organoid (GCO) models in which the organoid and immune cells are in free contact and sufficiently react with each other exist. In this study, we aimed to create a coculture model in which immune cells can move freely and stay in contact with GCOs. We coated the bottom surface of the plate with Matrigel and adhered stem cells to the Matrigel surface, instead of completely embedding them in Matrigel to culture organoids. This method allowed GCOs to grow on the Matrigel surface while maintaining a three-dimensional structure and reproducing the characteristics of the patient’s cancer. We cocultured GCOs and immune cells. Using this model, immune cells could freely move and were in sufficient contact with the cultured GCOs. Our model allowed real-time observation of the immune response and tumor destruction with time. In addition, the GCO killing assay was assessed with natural killer cells from the same patient. This organoid culture model enabled repeated evaluation of the GCO killing assay with various immune cells in vitro. We established a new experimental model that allowed free movement of immune cells and sufficient contact with GCOs. Using this model, it may be possible to predict the effects of immune checkpoint inhibitors in vitro (using GCOs) before administering them to patients.
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spelling doaj.art-2755e1f1a91045c59c71c285b926c7ca2024-02-01T06:32:15ZengElsevierHeliyon2405-84402024-01-01101e23520Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoidsHiroshi Ota0Kazuaki Tanabe1Yoshihiro Saeki2Yuki Takemoto3Emi Chikuie4Naoya Sakamoto5Hideki Ohdan6Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Science, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, JapanDepartment of Perioperative and Critical Care Management, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan; Corresponding author.Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Science, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan; Division of Endoscopic Surgery, Hofu Institute of Gastroenterology, Hiroshima University Hospital, 14-33 Ekiminami-machi, Yamaguchi, 747-0801, JapanDepartment of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Science, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, JapanDepartment of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Science, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, JapanDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, JapanDepartment of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Science, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, JapanOrganoid technology, a novel 3D cell culture system, can reproduce a patient’s cancer and may be a novel immunotherapy experimental model. However, currently no gastric cancer organoid (GCO) models in which the organoid and immune cells are in free contact and sufficiently react with each other exist. In this study, we aimed to create a coculture model in which immune cells can move freely and stay in contact with GCOs. We coated the bottom surface of the plate with Matrigel and adhered stem cells to the Matrigel surface, instead of completely embedding them in Matrigel to culture organoids. This method allowed GCOs to grow on the Matrigel surface while maintaining a three-dimensional structure and reproducing the characteristics of the patient’s cancer. We cocultured GCOs and immune cells. Using this model, immune cells could freely move and were in sufficient contact with the cultured GCOs. Our model allowed real-time observation of the immune response and tumor destruction with time. In addition, the GCO killing assay was assessed with natural killer cells from the same patient. This organoid culture model enabled repeated evaluation of the GCO killing assay with various immune cells in vitro. We established a new experimental model that allowed free movement of immune cells and sufficient contact with GCOs. Using this model, it may be possible to predict the effects of immune checkpoint inhibitors in vitro (using GCOs) before administering them to patients.http://www.sciencedirect.com/science/article/pii/S2405844023107286OrganoidsGastric cancerImmunotherapyPeripheral blood mononuclear cellsNatural killer cells
spellingShingle Hiroshi Ota
Kazuaki Tanabe
Yoshihiro Saeki
Yuki Takemoto
Emi Chikuie
Naoya Sakamoto
Hideki Ohdan
Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids
Heliyon
Organoids
Gastric cancer
Immunotherapy
Peripheral blood mononuclear cells
Natural killer cells
title Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids
title_full Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids
title_fullStr Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids
title_full_unstemmed Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids
title_short Establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids
title_sort establishment of a novel overlay culture method that enables immune response assessment using gastric cancer organoids
topic Organoids
Gastric cancer
Immunotherapy
Peripheral blood mononuclear cells
Natural killer cells
url http://www.sciencedirect.com/science/article/pii/S2405844023107286
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