Investigation of in vitro effect of natural killer cells differentiated from adipogenic mesenchymal stem cells on ovarian cancer
Project no. 35 · Status: Kapanmış · 2016
Summary
Ovarian cancer is one of the most common cancers which takes/represents the second place among deaths from cancer in women. Since it shows its symptoms at a later stage, 70% of the patients pass away within the five years after diagnosis. Mesenchymal stem cells (MSC) are multipotent adult stem cells and because they originate from stroma, they also show the characteristics of “supporting cells”. These cells recently gained attention due to their importance for tissue microenvironment and their suppressive effects on immune system. They could be obtained from various tissues, such as bone marrow and adipose tissue and since they represent a favorable cell type for proliferation, they can be expanded in in vitro conditions via subculturing. Adipose tissue, which could generally be obtained easily and in massive amounts via surgical procedures, is a rich source of MSCs. Natural Killer cells are critical mediators of host immunity in cases of cellular malignancy and infection. It was shown with both preclicinal and clinical studies on mice and humans, respectively that, Natural Killer cells mediate strong antitumoral responses. Activation of functional NK cells; besides causing the release of chemokines and cytokines (especially INF shows strong regulatory effects on targeted cells), it leads to NK cell-mediated cytotoxicity (via releasing lytic molecules such as perforine and granzyme B) which in turn kills malignant cells through leading to apoptosis. In this project, in vitro effect of NK cells differentiated from adipogenic mesenchymal stem cells (AD-MSCs) on HeyA8 ovarian cancer cells was investigated. In scope of the study, differentiation to NK cells was done and characterized via analysing NK cell-specific antibody-CD314 by flow cytometry. The cells showing characteristics of NK cells were determined and then, co-cultured with HeyA8 cells. Presence of NK cells and their cytotoxic effect was determined in co-culturing media. It was shown that these cells stimulated apoptosis when they were co-cultured with HeyA8 cells. Based on the results obtained in this in vitro study on ovarian cancer cells, NK cells represent an efficient and effective cellular treatment model from the perspective of immunotherapeutic approach.