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Abstract Engineering human tissue with diverse cell types and architectures remains challenging. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca2+ oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient’s own induced pluripotent stem cells.

In response to injuries to the CNS, astrocytes enter a reactive state known as astrogliosis, which is believed to be deleterious in some contexts. Activated astrocytes overexpress intermediate filaments including glial fibrillary acidic protein (GFAP) and vimentin (Vim), resulting in entangled cells that inhibit neurite growth and functional recovery. Reactive astrocytes also secrete inflammatory molecules such as Lipocalin 2 (Lcn2), which perpetuate reactivity and adversely affect other cells of the CNS. Herein, we report proof-of-concept use of the packaging RNA (pRNA)-derived three-way junction (3WJ) motif as a platform for the delivery of siRNAs to downregulate such reactivity-associated genes. In vitro, siRNA-3WJs induced a significant knockdown of Gfap, Vim, and Lcn2 in a model of astroglial activation, with a concomitant reduction in protein expression. Knockdown of Lcn2 also led to reduced protein secretion from reactive astroglial cells, significantly impeding the perpetuation of inflammation in otherwise quiescent astrocytes. Intralesional injection of anti-Lcn2-3WJs in mice with contusion spinal cord injury led to knockdown of Lcn2 at mRNA and protein levels in vivo. Our results provide evidence for siRNA-3WJs as a promising platform for ameliorating astroglial reactivity, with significant potential for further functionalization and adaptation for therapeutic applications in the CNS.

The purpose of this study is to fill a gap about Edoardo Sanguineti’s translations in the current bibliography. Despite the fact that Friedmar Apel’s method brings a sweeping change to research in the field of translation studies and many works about Sanguineti’s activity have been published in recent years, an overall analysis regarding Seneca’s Phaedra still doesn’t exist. The drama was translated for Luca Ronconi’s theatrical production, performed at Teatro Stabile di Roma in 1969. Both play and translation were harshly criticized for their rhetoric, declamation and forceful emphasis: the same critics were directed to the original text. This study tries to show that Sanguineti perfectly knows that in the Seneca’s play – as Eliot said – «the drama is all in the word». Therefore Sanguineti creates a new style of translation, that he calls «oracolese»: its idiosyncratic syntax (caused by reproduction of ordo verborum), assonances and alliterations, alienating commixture between high literal tradition and colloquial Italian grammar are strictly related to the mise-en-scene. Sanguineti realizes that Seneca’s dramas’ static plot has a special strength and – because «in translation there is no other speaker than translator» – this is the strongest relation with the original, the only point of contact possible.