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Case study: 3D pancreas model to capture intratumoral pressure

Influence of interstitial fluid pressure and flow on chemoresistance in PDAC organoids.

About the research

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal cancers due to a high chemoresistance and poor vascularization, which results in an ineffective systemic therapy. PDAC is characterized by a high intratumoral pressure, which is not captured by current 2D and 3D in vitro models.

Together with Leiden Academic Centre for Drug Research (LACDR) we developed a 3D microfluidic interstitial flow model to capture the intratumoral pressure in PDAC. In this study, pancreatic cancer organoids were cultured in an ECM gel in the OrganoPlate® 3-lane 40. Flow was applied parallel and orthogonal to the organoids in the gel, in order to compare lateral flow with interstitial flow through the tissue.

This project received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement no 602783. The full study was published in Int. J. Mol. Sci. 2019, 20, 4647.

Custom model

We developed a 3D cell culture modality for studying intratissue pressure and flow. By subjecting the PDAC cell line to interstitial flow, we showed that:

  • cultures under interstitial flow showed reduced proliferation compared to lateral flow
  • PDAC organoids exposed to interstitial flow showed a higher EC50 value for gemcitabine in comparison to lateral perfusion and 2D culture

Improved predictive value

The model exhibits more predictive capabilities than conventional 2D cell culture, is less time-consuming, and more scalable and accessible than animal models. This increase in microphysiological relevance might support improved efficiency in the drug development pipeline.

Key results

  • Time-efficient 3D culture modality
  • Improved predictive value compared to conventional 2D cell culture
  • More scalable, affordable, and ethical than animal models

About Cell-Cell Interactions

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