Engineering a 3D Novel in vitro Perfusion System for Pancreatic Cancer Research

Abstract

The Pancreatic Ductal Adenocarcinoma is a malignant aggressive disease corresponding to a low survival rate of 5 years, only between 5 to 7%. This is mainly due to the high complexity and density of the malignant tumour microenvironment which difficult the efficiency of potential treatments and furthermore, to the disease’s progression and inhibition of apoptotic pathways. Over the last years, Tissue Engineering has been gaining an even more prominent role regarding the construction of tri-dimensional (3D) in vitro culture systems that enable a better comprehension of the physicochemical properties and a more realistic recapitulation of the structure of tumoural tissues. In this study, it is described for the first time, the use of a perfusion bioreactor for the culture of pancreatic cancer cells in 3D porous polyurethane scaffolds previously coated with one of the most abundant proteins in the extracellular matrix, the fibronectin. This dynamic culture system allowed a higher proliferation of the tumoural cells as well as a greater cell viability when compared to static culture systems. The addition of a chemotherapy agent also showed a higher resistance by the cells cultured in the bioreactor in addition to a lower percentage of cells in apoptosis. The results obtained suggest the great potentiality of perfusion bioreactors in high throughput studies regarding the in vitro culture of cancer cells for the vascularization mimicry of in vivo systems, including drug and treatment screening for patients detected with pancreatic cancer.