Patient-derived pancreatic cancer-on-a-chip recapitulates the tumor microenvironment

Muhammad R Haque; Caitlin R Wessel; Daniel D Leary; Chengyao Wang; Abhinav Bhushan; Faraz Bishehsari

doi:10.1038/s41378-022-00370-6

Patient-derived pancreatic cancer-on-a-chip recapitulates the tumor microenvironment

Microsyst Nanoeng. 2022 Mar 31:8:36. doi: 10.1038/s41378-022-00370-6. eCollection 2022.

Authors

Muhammad R Haque¹, Caitlin R Wessel², Daniel D Leary¹, Chengyao Wang³, Abhinav Bhushan³, Faraz Bishehsari¹

Affiliations

¹ Division of Digestive Diseases, Rush Center for Integrated Microbiome & Chronobiology Research, Rush University Medical Center, Chicago, IL 60612 USA.
² University of Louisville School of Medicine, Louisville, KY 40202 USA.
³ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616 USA.

Abstract

The patient population suffering from pancreatic ductal adenocarcinoma (PDAC) presents, as a whole, with a high degree of molecular tumor heterogeneity. The heterogeneity of PDAC tumor composition has complicated treatment and stalled success in clinical trials. Current in vitro techniques insufficiently replicate the intricate stromal components of PDAC tumor microenvironments (TMEs) and fail to model a given tumor's unique genetic phenotype. The development of patient-derived organoids (PDOs) has opened the door for improved personalized medicine since PDOs are derived directly from patient tumors, thus preserving the tumors' unique behaviors and genetic phenotypes. This study developed a tumor-chip device engineered to mimic the PDAC TME by incorporating PDOs and stromal cells, specifically pancreatic stellate cells and macrophages. Establishing PDOs in a multicellular microfluidic chip device prolongs cellular function and longevity and successfully establishes a complex organotypic tumor environment that incorporates desmoplastic stroma and immune cells. When primary cancer cells in monoculture were subjected to stroma-depleting agents, there was no effect on cancer cell viability. However, targeting stroma in our tumor-chip model resulted in a significant increase in the chemotherapy effect on cancer cells, thus validating the use of this tumor-chip device for drug testing.

Keywords: Engineering; Materials science.