Fast wide-volume functional imaging of engineered in vitro brain tissues

Palazzolo, G., Moroni, M., Soloperto, A., Aletti, G., Naldi, G., Vassalli, M. , Nieus, T. and Difato, F. (2017) Fast wide-volume functional imaging of engineered in vitro brain tissues. Scientific Reports, 7, 8499. (doi: 10.1038/s41598-017-08979-8) (PMID:28819205) (PMCID:PMC5561227)

Abstract

The need for in vitro models that mimic the human brain to replace animal testing and allow high-throughput screening has driven scientists to develop new tools that reproduce tissue-like features on a chip. Three-dimensional (3D) in vitro cultures are emerging as an unmatched platform that preserves the complexity of cell-to-cell connections within a tissue, improves cell survival, and boosts neuronal differentiation. In this context, new and flexible imaging approaches are required to monitor the functional states of 3D networks. Herein, we propose an experimental model based on 3D neuronal networks in an alginate hydrogel, a tunable wide-volume imaging approach, and an efficient denoising algorithm to resolve, down to single cell resolution, the 3D activity of hundreds of neurons expressing the calcium sensor GCaMP6s. Furthermore, we implemented a 3D co-culture system mimicking the contiguous interfaces of distinct brain tissues such as the cortical-hippocampal interface. The analysis of the network activity of single and layered neuronal co-cultures revealed cell-type-specific activities and an organization of neuronal subpopulations that changed in the two culture configurations. Overall, our experimental platform represents a simple, powerful and cost-effective platform for developing and monitoring living 3D layered brain tissue on chip structures with high resolution and high throughput.

• Item Type: Articles
• Additional Information: The present work has been funded by Compagnia di San Paolo (grant agreement n. EPFD0041).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Vassalli, Professor Massimo
• Authors: Palazzolo, G., Moroni, M., Soloperto, A., Aletti, G., Naldi, G., Vassalli, M., Nieus, T., and Difato, F.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Published Online: 17 August 2017
• Copyright Holders: Copyright © The Authors 2017
• First Published: First published in Scientific Reports 7:8499
• Publisher Policy: Reproduced under a Creative Commons license