期刊
LAB ON A CHIP
卷 21, 期 19, 页码 3675-3685出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1lc00350j
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资金
- National Institutes of Health [U01 HL143403, R01 CA254110, UL1 TR002529, R01 CA211098, R01 CA124586]
- Purdue University Center for Cancer Research [P30 CA023168]
- Walther Embedding Program in Physical Sciences in Oncology
- PCCR [P30 CA023168]
- IUSCC [P30 CA082709]
- Walther Cancer Foundation
The pancreatic acinus is a functional unit of the exocrine pancreas and understanding its pathobiology is crucial for pancreatic diseases. A pancreatic acinus-on-chip (PAC) model has been developed using reprogrammed pancreatic cancer cells, providing a new and reliable platform for studying the initiation and progression of pancreatic cancers.
A pancreatic acinus is a functional unit of the exocrine pancreas producing digest enzymes. Its pathobiology is crucial to pancreatic diseases including pancreatitis and pancreatic cancer, which can initiate from pancreatic acini. However, research on pancreatic acini has been significantly hampered due to the difficulty of culturing normal acinar cells in vitro. In this study, an in vitro model of the normal acinus, named pancreatic acinus-on-chip (PAC), is developed using reprogrammed pancreatic cancer cells. The developed model is a microfluidic platform with an epithelial duct and acinar sac geometry microfabricated by a newly developed two-step controlled viscous-fingering technique. In this model, human pancreatic cancer cells, Panc-1, reprogrammed to revert to the normal state upon induction of PTF1a gene expression, are cultured. Bioinformatic analyses suggest that, upon induced PTF1a expression, Panc-1 cells transition into a more normal and differentiated acinar phenotype. The microanatomy and exocrine functions of the model are characterized to confirm the normal acinus phenotypes. The developed model provides a new and reliable testbed to study the initiation and progression of pancreatic cancers.
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