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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

DEVELOPMENT OF A MICROFLUIDIC MODEL OF A PANCREATIC ACINUS

Stephanie Michele Venis (7022999) 16 August 2019
Pancreatic Ductal Adenocarcinoma (PDAC) continues to have a dismally low survival rate due to late diagnosis and poor treatment options. Therefore, there is a need to understand the early stages and progression of the disease. PDAC is known to have two types of cells of origin: ductal cells or acinar cells. Since acinar-derived PDAC is thought to be the more malignant of the two, it was chosen as the focus of this work. Most studies of acinar cells as they relate to PDAC are accomplished by using animal models such as genetically engineered mouse models. While this method yields a large amount of insight into the progression of the disease and the role of specific genes, it has the drawbacks of being very time and resource intensive. The quicker and less costly alternative is <i>in vitro </i>culture. Specifically, here we have developed a microfluidic model which can incorporate a key aspect of the extracellular matrix (ECM), type I collagen, and mimics the 3D geometry of an <i>in vivo </i>acinus. Most attempts at <i>in vitro </i>culture have been limited by the fact that isolated acinar cells show a decrease in the amount of digestive enzymes they secrete as culture continues. For this reason, we are using a reprogrammed cancer cell line. These cells can be induced with doxycycline to express PTF1a, which allows the cells to adapt acinar characteristics, such as the production of digestive enzymes. We were able to successfully culture and induce PTF1a in these cells within our chip. We showed that the cells exhibit no invasion into the collagen matrix once PTF1a is expressed, thus eliminating a key aspect of cancer cell culture. The cells grown in the chip are confirmed to be producing PRSS2, the digestive enzyme trypsinogen. Collectively, this suggests that we have produced healthy acinar cells growing in the same configuration that they would <i>in vivo. </i>This has many applications in the study of pancreatic ductal adenocarcinoma, as we have developed way to culture reprogramed cancer cells as their benign precursors and maintain acinar characteristics <i>in vitro.</i> It will also have applications in the study of many other pancreatic diseases by providing an <i>in vitro</i> model of a healthy, functional acinus.

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