Discipline: Biological Sciences
Subcategory: Biomedical Engineering
Angel Jayleen Leon - University of Washington
Co-Author(s): Elijah Weber, Lindsay Henderson, and Edward J. Kelly, University of Washington, Seattle, WA
Cisplatin is used as a chemotherapy agent against aggressive cancers. While cisplatin remains as an effective therapeutic for treating cancer, the kidneys remain a primary target for damage. The nephrotoxicity of cisplatin was evaluated in this study using LLCPK-1 cells, fetal proximal tubule epithelial cells (PTEC), and adult PTECs. Initial experiments were performed in 2D cell culture and further evaluated in the 3D microphysiological system (MPS). The MPS is being used as a model of cell culture ex vivo and previous developments have shown their utility to mirror the human body in regards to the proximal tubule of the kidney. We compared the cellular responses to different concentrations of cisplatin, using both traditional 2D cell culture techniques as well as the 3D MPS. In 2D cell culture, LLCPK-1 cells were the most sensitive cells to cisplatin compared to adult and fetal PTECs. In the MPS, adult cells that were exposed to 25uM of cisplatin showed signs of toxicity via morphological changes and the presence of dead cells identified using a live/dead stain kit. The Kelly lab believes successfully modeling nephrotoxicity using the MPS will translate towards a fully-functioning human model on a chip. The human model on a chip will not only limit the use of animal testing, but serve as a preclinical system to assess the human cellular response to new chemical entities. Future experiments will involve an increased duration of exposure to accurately represent the treatment duration in the clinic. In addition we are also investigating compounds that could be potentially protective against cisplatin.
Funder Acknowledgement(s): Anne Dinning and Michael Wolf for their donation to the GenOM project, the University of Washington GenOM Project, (NIH 5R25HG007153-03), UH3TR000504 (NCATS), 83573801 (USEPA), P30ES007033 (NIEHS) grants, The Drug Metabolism Transport and Pharmacogenetics Research Fund (University of Washington School of Pharmacy).
Faculty Advisor: Edward Kelly,