The ␤-cells in the pancreatic islets of Langerhans are the targets of autoreactive T-cells and are destroyed in type 1 diabetes. Macrophage-derived interleukin-1␤ ( I L -1␤) is important in eliciting ␤-cell dysfunction and initiating ␤-cell damage in response to microenvironmental changes within islets. In particular, IL-1␤ c a n impair glucose-stimulated insulin production in ␤-c e l l s in vitro and can sensitize them to Fas (CD95)/FasLtriggered apoptosis. In this report, we have examined the ability to block the detrimental effects of IL-1␤ b y genetically modifying islets by adenoviral gene transfer to express the IL-1 receptor antagonist protein. We demonstrate that adenoviral gene delivery of the cDNA encoding the interleukin-1 receptor antagonist protein (IL-1Ra) to cultured islets results in protection of human islets in vitro against IL-1␤-induced nitric oxide formation, impairment in glucose-stimulated insulin production, and Fas-triggered apoptosis activation. Our results further support the hypothesis that I L -1␤ antagonism in in situ may prevent intra-islet proinsulitic inflammatory events and may allow for an in vivo gene therapy strategy to prevent insulitis and the consequent pathogenesis of diabetes. D i a b e t e s 48: [1730][1731][1732][1733][1734][1735][1736] 1999

The demands of tissue engineering have driven a tremendous amount of research effort in 3D tissue culture technology and, more recently, in 3D printing. The need to use 3D tissue culture techniques more broadly in all of cell biology is well-recognized, but the transition to 3D has been impeded by the convenience, effectiveness, and ubiquity of 2D culture materials, assays, and protocols, as well as the lack of 3D counterparts of these tools. Interestingly, progress and discoveries in 3D bioprinting research may provide the technical support needed to grow the practice of 3D culture. Here we investigate an integrated approach for 3D printing multicellular structures while using the same platform for 3D cell culture, experimentation, and assay development. We employ a liquid-like solid (LLS) material made from packed granular-scale microgels, which locally and temporarily fluidizes under the focused application of stress and spontaneously solidifies after the applied stress is removed. These rheological properties enable 3D printing of multicellular structures as well as the growth and expansion of cellular structures or dispersed cells. The transport properties of LLS allow molecular diffusion for the delivery of nutrients or small molecules for fluorescence-based assays. Here, we measure viability of 11 different cell types in the LLS medium, we 3D print numerous structures using several of these cell types, and we explore the transport properties in molecular time-release assays.

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