A novel microfluidic 3D platform for culturing pancreatic ductal adenocarcinoma cells: comparison with in vitro cultures and in vivo xenografts

Meike Beer,Nirmala Kuppalu,Matteo Stefanini,Julia Schuette,Christian Schmees,Martin Stelzle,Sagar Manoli,Armando Casazza,Ingo Schulz,Holger Becker,Annarosa Arcangeli

doi:10.1038/s41598-017-01256-8

Abstract

The integration of microfluidics and cell biology has reached a significant milestone with the development of “organ-on-chips”, smart technological platforms that, once applied to the study of human diseases, such as cancer, might ultimately contribute to design personalised treatments and hence improve health outcomes. This paper reports that the combination of microfluidics and dielectrophoresis (DEP) allows to culture different pancreatic ductal adenocarcinoma (PDAC) human cell lines into a cyclic olefin polymer (COP) chamber (HepaChip®), enriched by the extracellular matrix (ECM) protein collagen. We show that PDAC cells cultured into the HepaChip® (1) are vital and grow, provided they properly attach to collagen; (2) show morphological appearance and growth characteristics closer to those of cells grown as spheroids than as classical 2 dimensional (2D) in vitro cultures. Finally, preliminary experiments show that PDAC cells respond to high doses of Cisplatin perfused through the chip. Overall, the present microfluidic platform could be exploited in the future for a personalised approach to PDAC.

Highlights

The deciphering of tumour biomolecular features and growth dynamics and the identification of novel targeted therapeutic strategies is being one of the major challenges in oncological research
We used three different human pancreatic ductal adenocarcinoma (PDAC) cell lines (BxPC3, PANC1 and MiaPaCa2), whose growth characteristics were first analysed in 2 dimensional (2D) (Fig. 1) and spheroid 3D (Fig. 2) cultures
All the PDAC cells in 2D cultures are vital after 48 hours of incubation, as witnessed by the Calcein/Propidium Iodide (PI) staining (Fig. 1C)

Summary

Introduction

The deciphering of tumour biomolecular features and growth dynamics and the identification of novel targeted therapeutic strategies is being one of the major challenges in oncological research. While in vitro 2D cultures have been the cornerstone of pre-clinical cancer research, there is increasing evidence that cells grown in 2D monolayers do not accurately reflect the biological complexity of tumours. They lack the complex extracellular matrix (ECM)-cancer interactions as well as intra-tumoral gradients in pH, oxygen and nutrients, which have been found in cancers in vivo. These weaknesses can explain why many drugs, that pass pre-clinical in vitro testing, fail in the patients[3,4,5,6].

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Conclusion