掺入人类 iPSC 衍生的基质细胞可创建具有异质癌症相关成纤维细胞的胰腺癌类器官。
Incorporation of human iPSC-derived stromal cells creates a pancreatic cancer organoid with heterogeneous cancer-associated fibroblasts.
发表日期：2023 Nov 12
作者：
Kenta Takeuchi, Shunsuke Tabe, Kenta Takahashi, Kenji Aoshima, Megumi Matsuo, Yasuharu Ueno, Yoichi Furukawa, Kiyoshi Yamaguchi, Masayuki Ohtsuka, Soichiro Morinaga, Yohei Miyagi, Tomoyuki Yamaguchi, Naoki Tanimizu, Hideki Taniguchi
来源：
Stem Cell Research & Therapy
摘要：
胰腺导管腺癌（PDAC）的侵袭性受到肿瘤微环境（TME）的影响。在这项研究中，为了体外概括 PDAC TME，我们将源自患者的 PDAC 细胞与源自人类诱导多能干细胞 (hiPSC) 的间充质和血管内皮细胞共培养，以在空气-液体中创建融合的胰腺癌类器官 (FPCO)界面。 FPCO 被进一步诱导类似于 PDAC 组织的两个不同方面。静止的 FPCO 具有耐药性，可能是因为 TME 由丰富的细胞外基质蛋白组成，这些蛋白是由 hiPSC 衍生的各种类型的癌症相关成纤维细胞 (CAF) 分泌的。增殖性 FPCO 在抗癌药物治疗后可以重新增殖，这表明这种类型的 FPCO 将有助于研究 PDAC 复发。因此，我们生成了 PDAC 类器官，它概括了 PDAC 组织的异质性，是筛选抗癌药物的潜在平台。版权所有 © 2023 作者。由爱思唯尔公司出版。保留所有权利。
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.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.