Development of a transplantable artificial ovary (TAO) to restore fertility in cancer patients - Julie Vanacker - Belgium

In order to restore endocrine function and fertility in patients suffering from cancer with a high risk of ovarian involvement, my project is to develop a transplantable artificial ovary (TAO). This artificial ovary would contain isolated ovarian follicle s, as they are encapsulated in a basement membrane separating them from capillaries, white blood cells and nerves, and ovarian cells isolated from a new ovarian sample after cancer treatment. Despite our encouraging results obtained with a high-M-alginat e matrix, its degradation rate was slow after one week grafting in mice. Moreover, the follicular recovery rate must be improved. The aim of my period at the Department of Biotechnology, NTNU, would thus be to modulate the matrix composition in order to improve its degradation rate and to allow cell-cell and cell-matrix interactions. Indeed, the biological inertness of alginate is well-known and has largely hampered its use when cell adhesion is mandatory for survival and proliferation. Three different strategies will be studied: - to mix alginate with chitosan, as it shows cellular aggregation properties and is biodegradable - to couple alginate with RGD peptides, which are interacting with integrins present in the cell membrane in order to result in anchorage of cells to alginate gels - to use periodate oxidised alginates to increase its degradation rate Upon the achievement of stable gel systems, the distribution of polymers in the gels will be studied by confocal laser scanning microscopy (CLSM), and mechanical properties with rheological characterization and stability/degradability in physiological solutions. Moreover, the degradation rate and cellular interactions of the different materials will be studied in vitro and compared to the high-M-al ginate matrix I previously used. Therefore, immunostaining/CLSM will be used to characterize encapsulated cells regarding follicle/cell recovery, viability, proliferation and morphology.