Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice

<p>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. How...

Täydet tiedot

Bibliografiset tiedot
Päätekijät: Jin, Y, Mikhailova, E, Lei, M, Zhou, L, Bayley, H, Cowley, SA, Sun, T, Yang, X, Zhang, Y, Liu, K, Catarino da Silva, D, Campos Soares, L, Bandiera, S, Szele, FG, Molnár, Z
Aineistotyyppi: Journal article
Kieli:English
Julkaistu: Springer Nature 2023
Kuvaus
Yhteenveto:<p>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 Ca<sup>2+</sup>&nbsp;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&rsquo;s own induced pluripotent stem cells.</p>