RRC ID 77374
Author Takeuchi K, Tabe S, Takahashi K, Aoshima K, Matsuo M, Ueno Y, Furukawa Y, Yamaguchi K, Ohtsuka M, Morinaga S, Miyagi Y, Yamaguchi T, Tanimizu N, Taniguchi H.
Title Incorporation of human iPSC-derived stromal cells creates a pancreatic cancer organoid with heterogeneous cancer-associated fibroblasts.
Journal Cell Rep
Abstract 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.
Volume 42(11)
Pages 113420
Published 2023-11-12
DOI 10.1016/j.celrep.2023.113420
PII S2211-1247(23)01432-8
PMID 37955987
MeSH Cancer-Associated Fibroblasts* / metabolism Carcinoma, Pancreatic Ductal* / pathology Cell Line, Tumor Endothelial Cells / metabolism Humans Induced Pluripotent Stem Cells* / metabolism Organoids / metabolism Pancreatic Neoplasms* / pathology Stromal Cells / metabolism Tumor Microenvironment
IF 8.109
Human and Animal Cells 293T(RCB2202)
DNA material CSII-EF-MCS-IRES2-hKO1 (RDB07915)