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.
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/8979923 |
| Date | 16 August 2019 |
| Creators | Stephanie Michele Venis (7022999) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/DEVELOPMENT_OF_A_MICROFLUIDIC_MODEL_OF_A_PANCREATIC_ACINUS/8979923 |
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