Modelling of the multicellular tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) on a fit-for-purpose biochip for preclinical drug discovery
Alina Deipenbrock, Benedict Wilmes, Thomas Sommermann, Nader Abdo, Kyra Moustakas, Martin Raasch, Knut Rennert, Nicole Teusch
Abstract
continuous flow for 72 h, resulted in a significantly reduced viability of PDAC spheroids without affecting vascular integrity. Furthermore, dynamic perfusion with peripheral mononuclear blood cells (PBMC)-derived monocytes resulted in an immune cell migration through the endothelium into the spheroids. After 72 h of infiltration, monocytes differentiated into macrophages which polarized into the M2 phenotype. The polarization into M2 macrophages persisted for at least 168 h, verified by expression of the M2 marker CD163 which increased from 72 h to 168 h, while the M1 markers CD86 and HLA-DR were significantly downregulated. Overall, the described spheroid-on-chip model allows the evaluation of novel therapeutic strategies by mimicking and targeting the complex TME of PDAC.