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- W2980574136 abstract "Organotypic culture models developed using 3D conditions recapitulate tissue-specific structural features and cell-cell interactions more accurately than conventional 2D cultures. Our goal is to optimize culture conditions which promote the survival and proliferation of multiple myeloma (MM) cells and could serve as a platform for molecular mechanistic, clinical biomarker and pharmacodynamic marker studies using immune-modulatory compounds (IMIDs) and other myeloma drugs alone and in combination. Using gas permeable microfluidic devices (MFDs), we cultured and compared growth/morphologic properties of six multiple myeloma cell lines, MM1.S, MM1.SPR, H929, H929PR, H929-220R and RPMI-8226 in 2D and 3D conditions. Pomalidomide and CC-220 resistant cell lines were originally developed in our group by culturing them with increasing concentrations of these drugs. Morphologically, cells grown in 3D conditions appeared to have higher tendency of forming spheroids. Cell lines grown in 3D conditions demonstrated higher proliferation index compared to 2D conditions. To further study the effects of other components of MM tumor micro-environment on Pomalidomide response, we optimized the culture conditions to co-culture MM cell lines with bone marrow stromal cells. The co-culture of bone marrow stromal cells, HS5 with MM cell line H929 protected Ikaros degradation induced by Pomalidomide. Interestingly, CD44 expression in H929 cells was upregulated in co-culture conditions with stromal cells. We then utilized these optimized 3D and 3D-stromal-media culture conditions to culture primary bone marrow bone nuclear cells (BMMCs) from MM patients. Our initial experiments demonstrate higher survival and proliferation of BMMCs cultured under 3D conditions in the MFD with maintained expression of oncogenic receptors, CD138 and CD38. These culture conditions are currently being optimized to study the (1) drug effects in MM and immune cells alone and in combination and (2) long term growth of primary Myeloma cells in these conditions for ex vivo manipulation and downstream molecular and biological effects." @default.
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- W2980574136 date "2019-10-01" @default.
- W2980574136 modified "2023-10-16" @default.
- W2980574136 title "Modeling tumor microenvironment interactions of IMID sensitive and resistant cells in 3D organotypic culture models" @default.
- W2980574136 doi "https://doi.org/10.1016/j.clml.2019.09.136" @default.
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