Abstract 332: Nanofibrillar cellulose hydrogel as 3D culture matrix towards the development of tumor models

Introduction. Physiologically relevant and robust in vitro cell models are needed for cancer model development, as well as standard cell-based drug screening assays. These models and assays may require the use of well-established cancer cell-lines or primary patient-derived cells. It is well known that three-dimensional (3D) cell culture provides a more in vivo -like environment for cells compared to traditional 2D monolayer culture. GrowDex®, a nanofibrillar cellulose (NFC) hydrogel, derived from the Birch tree, has been shown to reproducibly support the culture of many different cell types in 3D. Many animal derived hydrogels contain growth factors, other biological signaling molecules and unknown amounts of different ECM proteins, and have also suffered from variation between lots. The tunable stiffness, shear thinning properties and room-temperature stability, enable GrowDex to be used in a multitude of applications with a wide variety of different cell types and tissues. Additionally, cellulase enzyme (GrowDase™) treatment allows the recovery of cells or multicellular structures without impact to cell viability, phenotype or function. Methods and Results. Cancer cells derived from either solid tumor (e.g. osteosarcoma or breast cancer) or liquid biopsies (e.g. pleural or ascites effusion) require different culturing conditions. Studies have shown that GrowDex provides a suitable inert matrix where anchorage dependent and independent cancer cells can be cultured for short- or long-term studies, without observing uncontrolled matrix induced effects. Cells were seen to form round well-defined spheroids or multicellular structures. Additionally, co-cultures of cancer cells with fibroblasts provided a more physiologically relevant environment for the investigation of cell-cell effects on microtissue formation. When cells were seeded with different cell ratios, microtissues showed different morphologies and sizes. GrowDex has also been used successfully for the culture and characterization of an intensively pigmented cell line derived from a highly aggressive NRAS mutated cutaneous melanoma. Cultured cells maintained their natural in vivo behavior and morphology, as well as increasing the deep brown pigmentation staining. In addition, GrowDex has been shown to be an optimum matrix for use with patient derived cancer (PDC) cells cultured for use in drug screening tests for personalized medicine. Differences in drug responses with the PDC cells in 2D and 3D c