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Keywords = cell line organoids (CLOs)

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16 pages, 4069 KiB  
Article
Pancreatic Cancer 3D Cell Line Organoids (CLOs) Maintain the Phenotypic Characteristics of Organoids and Accurately Reflect the Cellular Architecture and Heterogeneity In Vivo
by Sara Noorani, Shannon R. Nelson, Neil T. Conlon, Justine Meiller, Ekaterina Shcheglova, Alice Usai, Jojanneke Stoof, Letizia Palanga, Fiona O’Neill, Sandra Roche, Maura B. Cotter, Niall Swan and Naomi Walsh
Organoids 2022, 1(2), 168-183; https://doi.org/10.3390/organoids1020013 - 12 Dec 2022
Cited by 3 | Viewed by 5956
Abstract
Pancreatic cancer is a highly lethal disease. Therapeutic resistance to chemotherapy is a major cause of treatment failure and recurrence in pancreatic cancer. Organoids derived from cancer stem cells (CSC) are promising models for the advancement of personalised therapeutic responses to inform clinical [...] Read more.
Pancreatic cancer is a highly lethal disease. Therapeutic resistance to chemotherapy is a major cause of treatment failure and recurrence in pancreatic cancer. Organoids derived from cancer stem cells (CSC) are promising models for the advancement of personalised therapeutic responses to inform clinical decisions. However, scaling-up of 3D organoids for high-throughput screening is time-consuming and costly. Here, we successfully developed organoid-derived cell lines (2.5D) from 3D organoids; the cells were then expanded and recapitulated back into organoids known as cell line organoids (CLOs). The 2.5D lines were cultured long term into 2D established cell lines for downstream comparison analysis. Experimental characterisation of the models revealed that the proliferation of CLOs was slightly faster than that of parental organoids. The therapeutic response to chemotherapeutic agents in 3D CLOs and organoids showed a similar responsive profile. Compared to 3D CLOs and organoids, 2D cell lines tended to be less responsive to all the drugs tested. Stem cell marker expression was higher in either 3D CLOs or organoids compared to 2D cell lines. An in vivo tumorigenicity study found CLOs form tumours at a similar rate to organoids and retain enhanced CSC marker expression, indicating the plasticity of CSCs within the in vivo microenvironment. Full article
(This article belongs to the Topic Human Current and Future Model Systems)
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