一种用于开发腹膜假黏液瘤类器官模型的组合培养策略。

A combinatorial culture strategy to develop pseudomyxoma peritonei organoid models.

作者信息

Varinelli Luca, Di Bella Marzia, Guaglio Marcello, Battistessa Davide, Pisati Federica, Cavalleri Tommaso, Milione Massimo, Martínez-Quintanilla Jordi, Caswell Patrick T, Baratti Dario, Kusamura Shigeki, Deraco Marcello, Gariboldi Manuela

机构信息

Molecular Epigenomics Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy.

Peritoneal Surface Malignancies Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy.

出版信息

J Surg Oncol. 2024 Nov;130(6):1213-1224. doi: 10.1002/jso.27850. Epub 2024 Oct 3.

Abstract

BACKGROUND AND OBJECTIVES

Few preclinical models of pseudomyxoma peritonei (PMP) have been developed, probably due to the tumor's low incidence and its peculiar characteristics of slow growth. Therefore, there is a need to develop more refined PMP models that better reflect its characteristics. The aim of the study is to develop a culture strategy to generate organoid models derived from PMP patient samples.

METHODS

We followed a strategy based on combinatorial culture conditions that include the different factors essential for PMP growth and that mimic the microenvironment present in the patients.

RESULTS

We cultured PMP samples in the presence of the various factors produced by the niche environment of PMP. We obtained 12 PMP organoid models, each of which grows under specific culture conditions. PMP-derived organoids show long-term expansion capacity and reproduce the genetic landscape and histological phenotype of the tumor of origin.

CONCLUSION

The organoids we developed faithfully reproduce the key features of PMP disease and will allow us to understand the biology of PMP. With them, we will be able to identify key regulatory networks that support PMP progression, providing a platform for multilevel preclinical testing, identify novel diagnostic biomarkers, and generate novel targets for patient treatments.

摘要

背景与目的

腹膜假黏液瘤(PMP)的临床前模型很少被开发出来,这可能是由于该肿瘤发病率低且生长缓慢的特殊特征。因此,需要开发更精细的PMP模型以更好地反映其特征。本研究的目的是制定一种培养策略,以生成源自PMP患者样本的类器官模型。

方法

我们采用了一种基于组合培养条件的策略,该条件包括PMP生长所必需的不同因素,并模拟患者体内存在的微环境。

结果

我们在PMP生态位环境产生的各种因素存在的情况下培养PMP样本。我们获得了12个PMP类器官模型,每个模型都在特定的培养条件下生长。源自PMP的类器官显示出长期扩增能力,并重现了原发肿瘤的基因图谱和组织学表型。

结论

我们开发的类器官忠实地再现了PMP疾病的关键特征,并将使我们能够了解PMP的生物学特性。借助它们,我们将能够识别支持PMP进展的关键调控网络,为多层次临床前测试提供平台,识别新的诊断生物标志物,并为患者治疗生成新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be36/11826015/30d50d1e5d70/JSO-130-1213-g006.jpg

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