Mesenchymal Stem Cells (MSCs) are widely used in therapeutic applications. Their plasticity and predisposition to differentiate into a variety of cell types, including those of the neuronal lineage, makes them ideal to study whether a selection of miRNAs may direct the differentiation of MSCs into neuroblasts or neuroblastoma to mature neurons. Following a short-listing, miR-107, 124 and 381 were selected as the most promising candidates for this differentiation. MSCs differentiated into cells of the neural lineage (Conditioned Cells) upon addition of conditioned medium (rich in microvesicles containing miRNAs) obtained from cultured SH-SY5Y neuroblastoma cells. Characterisation of stemness (including SOX2, OCT4, Nanog and HCG) and neural markers (including Nestin, MASH1, TUBB3 and NeuN1) provided insight regarding the neuronal state of each cell type. This was followed by transfection of the three miRNA antagonists and mimics, and quantification of their respective target genes. MiRNA target gene expression following transfection of MSCs with miRNA inhibitors and mimics demonstrated that these three miRNAs were not sufficient to induce differentiation. In conditioned cells the marginal changes in the miRNA target expression levels reflected potential for the modulation of intermediate neural progenitors and immature neuron cell types. Transfection of various combinations of miRNA inhibitors and/or mimics revealed more promise. Undoubtedly, a mix of biomolecules is being released by the SH-SY5Y in culture that induce MSCs to differentiate. Screening for those biomolecules acting synergistically with specific miRNAs will allow further combinatorial testing to elucidate the role of miRNA modulation.

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showed that, in the worst predicted scenario (median LOS corresponding to 12 days), 1146 C¼ /patient would be saved if ERAS protocols were applied. Conclusion* Besides of achieving lower LOS and fewer readmission rates, implementation of an ERAS program in AOC surgery leads to valuable hospital savings. Therefore, ERAS should be the standard practice for AOC surgeries.

Conclusion* Using a multimodal approach, including IHC and FACs, we demonstrate that the metastatic TME in HGSOC is significantly different to the primary TME. These findings provide an initial explanation as to why immune checkpoint inhibitors have failed in HGSOC and warrant further investigation.

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