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PDAC-on-chip for modeling of stromal and pancreatic cancer cell crosstalk. | LitMetric

PDAC-on-chip for modeling of stromal and pancreatic cancer cell crosstalk.

Biomater Sci

Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.

Published: December 2022

AI Article Synopsis

  • Pancreatic ductal adenocarcinoma (PDAC) mainly develops in the head of the pancreas and is significantly influenced by pancreatic stellate cells (PSCs), which alter the tumor microenvironment and affect drug delivery.
  • Researchers created a microfluidic model called PDAC-on-chip to mimic the interactions between PDAC cells and PSCs, facilitating the study of tumor progression and therapy testing.
  • The model showed changes in the behavior of fibroblasts when co-cultured with tumor cells, including alterations in morphology and increased secretion of IL-6 cytokines, validating its potential for drug efficacy evaluation and understanding PDAC's development.

Article Abstract

Pancreatic ductal adenocarcinoma (PDAC) mainly develops in the head of the pancreas, within the acino-ductal unit composed of acinar and ductal cells surrounded by pancreatic stellate cells (PSCs). PSCs strongly influence the tumor microenvironment by triggering an intense stromal deposition, which plays a key role in tumor progression and limits drug perfusion. We have developed a microfluidic model recreating the tumor-stroma crosstalk to replicate the steps of PDAC evolution towards the establishment of an efficient platform for innovative therapy validation. The multilayer PDAC-on-chip was designed to culture the PDAC cells and the PSCs embedded in a type I collagen gel in the top and bottom layers, respectively. The presence of a biomimetic nanofibrous membrane in the middle of the chip permits the control of interactions between the two cell lines and the easy analysis of the effects of the crosstalk on cell behavior. First, the PDAC-stromal cell relationship was evaluated under co-culture conditions on 24-well inserts including the PCL/Gel electrospun membrane. This simplified model shows that human fibroblasts change their morphology and secrete larger amounts of IL-6 cytokines in the presence of tumor cells, confirming the activation of stromal cells under co-culture. Then, the PDAC-on-chip system was validated by demonstrating that human fibroblasts seeded in a 3D collagen matrix in the bottom microchannel also change to a myofibroblast-like shape with increased expression of α-SMA and secrete larger amounts of IL-6 cytokines. This microfluidic system is suitable for the evaluation of drug efficacy and serves as a powerful tool for understanding the early evolution steps of PDAC.

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Source
http://dx.doi.org/10.1039/d2bm00881eDOI Listing

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