innovative cell technology

Abstract

In general, cancer refers to the development of abnormal cells that divide overpoweringly and are capable of destroying normal body tissue, proliferate continuously, migrate to different parts of the body, and promote the growth of new blood vessels. Since cancer is one of the most common obstacles to achieve desirable life expectancy in the world, speeding up the drug screening and find the best treatment is highly demanded. Survival rates are improving for many types of cancers, thanks to improvements in cancer screening and personalized therapies. Ovarian cancer is one of the major cancer with a high rate of female mortality globally every year and can be affected women of all ages but mostly after menopause. In the last recent years, not many broadly recognized pathogenesis and detection method were available, which able to explain the entire disease due to its heterogeneous nature. For instance, two-dimensional systems, animal models, and spheroids provided too much crucial information about the cancer environment and therapies, but they are not sufficient since they are lacking many factors to be close to in vivo situations. Hence, they are not fully capable to mimic the real body condition and tissue response against the drugs. Drawing on this need, several methods were applied to improve and decrease the limitations of cancer treatments. To overcome such problems here in the frame of this thesis, the novel microfluidic organ-on-a-chip-model called Mimetas is used, which is capable of tumor homology maintenance for a long time and mimics the microenvironment in vivo in the greatest degree compare with the other traditional models. Hence, drug sympathy is much better than the static old-fashioned condition. Mimetas is an OrganoPlate made by three different connected channels with the perfusion of fluid flow. ECM is inserted in the middle channel, cells and medium seeded against it. Then is placed on the rocker shaker to produce a flow. The absence of artificial membranes, enables free migration, invasion, and exchanges of various factors. In this thesis, the advantages of setting up the Ascites organoids on Mimetas plate and screening the capability of five different anticancer drugs including ATRA, VS10, Calyx, Doxorubicin, and Carboplatin was taken. Parallel to this work, the same ascites with the unchanged dosage of the mentioned drug that was used in Mimetas plate, tested in 96-multiwell plate in static condition. Comparison between the responses in static and microfluidic conditions helps us to understand better the tumor tissue response against the therapeutic compounds in the optimum dosage condition and recognizing their pros and cons. Cell Viability assay was done by cell titer Glo (Promega) in both conditions. Ascites organoid derived directly from the ovarian cancer patient from the Oncology Referral Center hospital in Aviano and then they set up on OraganoPlate to monitor their response. Comparison between the responding of different therapeutic compounds of static condition and this high throughput novel model microfluidic technology can develop the future personalized therapy experiments.