A Platform of Porous Biomaterials as 3D Culture Systems for Cancer Biology

L. Moroni, A. van Boxtel, C.A. van Blitterswijk, G.A. Higuera

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Background: The role of stem cells in tissue development and repair is beginning to be unravelled and will open remarkable opportunities to improve current medical treatments. Yet, the cascade of events that enable us to distinguish between abnormal and functional tissue morphogenesis is not well known and the potential involvement of stem cells in cancer initiation or tissue regeneration is still at an embryonic stage. Most biological studies rely on culturing cells onto two-dimensional (2D) substrates, which poorly reflect the three-dimensional (3D) environment that governs the physical, chemical, and biological processes at the heart of tissue development. Here, we introduce a library of 3D culture systems − scaffolds − with enhanced cell-material interactions.

Materials and Methods: 3D scaffolds made of biodegradable synthetic polymers were fabricated by either rapid prototyping, eletrospinning and their combination. Mesenchymal stem cells derived from bone marrow were isolated from patients after informed consent, seeded on the scaffolds and cultured for up to 35 days. Cell morphology was observed by scanning electron microscopy. Cell number and metabolic activity were quantified by DNA and alamar blue assays. Differentiation was assessed by gene expression, while extrfacellular matrix (ECM) formation by biochemical assays.

Results: 3D scaffolds with tailored mechanical and physichochemical properties could be fabricated by different processing technologies. While rapid prototyping resulted in the fabrication of scaffolds with controlled porosity at the macro scale, electrospinning enabled the creation of fibrillar meshes mimicking the physical micro and nano scale dimensions of native ECM. Nutrient availability had a profound effect on tissue formation in 2D and 3D. Despite steep nutrient concentration gradients in 3D scaffolds, stem cells proliferated while avoiding significant death. Cell migration into millimeter-size circular patterns in the scaffold’s pores was supported by ECM organization. Higher concentrations of nutrients controlled the rates of proliferation and did not induce differentiation markers. Furthermore, scaffolds with customized physicochemical and surface properties influenced stem cell morphology and activity.

Conclusions: These 3D scaffolds offer a new platform to study the mechanisms behind stem cell driven tissue morphogenesis and may play a role in cancer biology research to create organotypic 3D models to study cancer initiation and development, as well as the potential involvement of stem cells in these processes.
Original languageEnglish
Publication statusPublished - 7 Jul 2012
Event22nd Biennial Congress of the European Association for Cancer Research 2012 - Barcelona, Spain
Duration: 7 Jul 201212 Jul 2012
Conference number: 22


Conference22nd Biennial Congress of the European Association for Cancer Research 2012


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