Organotypic Slice Cultures as Preclinical Models of Tumor Microenvironment in Primary Pancreatic Cancer and Metastasis

Braun, Rüdiger; Lapshyna, Olha; Eckelmann, Susanne; Honselmann, Kim C.; Bolm, Louisa; Winkel, Meike ten; Deichmann, Steffen; Schilling, Oliver; Kruse, Charli; Keck, Tobias; Wellner, Ulrich F.; Bronsert, Peter; Brandenburger, Matthias

doi:10.3791/62541

Cited by 9 publications

(13 citation statements)

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“…However, the culture of immune cells requires the appropriate addition of IL‐2, especially when testing immunomodulatory drugs 49 . For specific culture methods, tissue slices are usually placed on a supporting tool, such as a Millipore filter insert, to navigate the air‐liquid interface culture 50 . However, these methods still result in intra‐slice gradients.…”

Section: Tissue Slicing Technology and Tissue Slicesmentioning

confidence: 99%

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Complex in vitro model: A transformative model in drug development and precision medicine

Wang,

Hu,

et al. 2024

Clinical Translational Sci

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In vitro and in vivo models play integral roles in preclinical drug research, evaluation, and precision medicine. In vitro models primarily involve research platforms based on cultured cells, typically in the form of two‐dimensional (2D) cell models. However, notable disparities exist between 2D cultured cells and in vivo cells across various aspects, rendering the former inadequate for replicating the physiologically relevant functions of human or animal organs and tissues. Consequently, these models failed to accurately reflect real‐life scenarios post‐drug administration. Complex in vitro models (CIVMs) refer to in vitro models that integrate a multicellular environment and a three‐dimensional (3D) structure using bio‐polymer or tissue‐derived matrices. These models seek to reconstruct the organ‐ or tissue‐specific characteristics of the extracellular microenvironment. The utilization of CIVMs allows for enhanced physiological correlation of cultured cells, thereby better mimicking in vivo conditions without ethical concerns associated with animal experimentation. Consequently, CIVMs have gained prominence in disease research and drug development. This review aimed to comprehensively examine and analyze the various types, manufacturing techniques, and applications of CIVM in the domains of drug discovery, drug development, and precision medicine. The objective of this study was to provide a comprehensive understanding of the progress made in CIVMs and their potential future use in these fields.

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Section: Tissue Slicing Technology and Tissue Slicesmentioning

confidence: 99%

“… 49 For specific culture methods, tissue slices are usually placed on a supporting tool, such as a Millipore filter insert, to navigate the air‐liquid interface culture. 50 However, these methods still result in intra‐slice gradients. Microfluidic techniques have been used to overcome this limitation.…”

Section: Tissue Slicing Technology and Tissue Slicesmentioning

confidence: 99%

Complex in vitro model: A transformative model in drug development and precision medicine

Wang,

Hu,

et al. 2024

Clinical Translational Sci

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“…Cultivation often takes place on inserts at the air-liquid-interface to ensure sufficient oxygenation and to prevent cell death due to hypoxia ( 120 , 126 ). Here, the composition of the medium is a critical factor, as certain media can support growth of certain cell types and thus influence the original tissue composition by driving selection of certain cell clones and phenotypes ( 119 , 127 ).…”

Section: Tumor Model Systems and Patient Avatarsmentioning

confidence: 99%

The challenge of making the right choice: patient avatars in the era of cancer immunotherapies

Kayser,

Brauer,

Susanne

et al. 2023

Front. Immunol.

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Immunotherapies are a key therapeutic strategy to fight cancer. Diverse approaches are used to activate tumor-directed immunity and to overcome tumor immune escape. The dynamic interplay between tumor cells and their tumor(immune)microenvironment (T(I)ME) poses a major challenge to create appropriate model systems. However, those model systems are needed to gain novel insights into tumor (immune) biology and a prerequisite to accurately develop and test immunotherapeutic approaches which can be successfully translated into clinical application. Several model systems have been established and advanced into so-called patient avatars to mimic the patient´s tumor biology. All models have their advantages but also disadvantages underscoring the necessity to pay attention in defining the rationale and requirements for which the patient avatar will be used. Here, we briefly outline the current state of tumor model systems used for tumor (immune)biological analysis as well as evaluation of immunotherapeutic agents. Finally, we provide a recommendation for further development to make patient avatars a complementary tool for testing and predicting immunotherapeutic strategies for personalization of tumor therapies.

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“…This procedure has been successfully applied to tumors from the liver ( 132 ), pancreas ( 133 , 134 ), stomach and gastroesophageal junction ( 135 ), lung ( 130 ), prostate and bladder ( 131 ) and from hepatic metastasis of CRC ( 136 ). At different time points, the slices can be evaluated to determine the level of tumor cell death and when immunotherapeutics were applied to investigate the proliferation and/or relocalization of immune cells ( 130 , 132 ).…”

Section: Patient Derived Materials For Therapy Selectionmentioning

confidence: 99%

Combination of multiple omics techniques for a personalized therapy or treatment selection

Massa,

Seliger

2023

Front. Immunol.

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Despite targeted therapies and immunotherapies have revolutionized the treatment of cancer patients, only a limited number of patients have long-term responses. Moreover, due to differences within cancer patients in the tumor mutational burden, composition of the tumor microenvironment as well as of the peripheral immune system and microbiome, and in the development of immune escape mechanisms, there is no “one fit all” therapy. Thus, the treatment of patients must be personalized based on the specific molecular, immunologic and/or metabolic landscape of their tumor. In order to identify for each patient the best possible therapy, different approaches should be employed and combined. These include (i) the use of predictive biomarkers identified on large cohorts of patients with the same tumor type and (ii) the evaluation of the individual tumor with “omics”-based analyses as well as its ex vivo characterization for susceptibility to different therapies.

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Organotypic Slice Cultures as Preclinical Models of Tumor Microenvironment in Primary Pancreatic Cancer and Metastasis

Cited by 9 publications

References 0 publications

Complex in vitro model: A transformative model in drug development and precision medicine

Complex in vitro model: A transformative model in drug development and precision medicine

The challenge of making the right choice: patient avatars in the era of cancer immunotherapies

Combination of multiple omics techniques for a personalized therapy or treatment selection

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