BROOC · Brain organoid-on-chip: a microfluidic platform to study neocortical development

Brain organoid-on-chip: a microfluidic platform to study neocortical development

Mammals possess a unique brain structure, the neocortex. To understand mammalian neocortical development and function, mouse models have been widely used due to their ease of use and the available genetic tools. However, the human neocortex has more than 1000 times more cells than the mouse neocortex. Hence, a human model of neocortical development to understand neurodevelopmental disorders such as autism spectrum disorders or intellectual disability is urgently needed. Neural 2D cultures derived for example from induced pluripotent stem cells (iPSC) have been used for many years but lack the complexity of the native tissue. In vivo, neural progenitor cells divide close to the ventricles on the apical side while newborn neurons migrate radially towards the pial or basal surface. Cerebral organoids still have only limited capacity to recapitulate human neocortical development and are hampered by a high variability. Hence, it is critical to further develop cerebral organoid models by improving the spatiotemporal unfolding of their anatomical organization, enhancing reproducibility, and making them more accessible for pharmacological interventions. A promising approach to provide controlled microenvironments that generate physiological conditions and allow controlled 3D spatio-temporal structuring is the use of Organ-on-chip (OoC) technology. To address this, the project outlines 3 specific objectives: 1: Screening hydrogel candidates with good cytocompatibility and optimized mechanical properties for human iPSC in vitro, to achieve optimal layers of the developing neuroepithelium. 2: Develop a protocol to fabricate multifunctional microfluidic platform by using rapid prototyping approaches and combining different types of biocompatible polymeric materials. Moreover, processes and protocols for hydrogel injection and generation of hydrogel layers as well as defined fluid flow will be established. Eventually to incorporate multi-electrode array (MEA) into the chip for high throughput monitoring of 3D microtissues. 3: Apply Brain Organoid-on-Chip to neocortical development study. In summary, we have developed a novel robust and physiologically-relevant human brain-on-chip system. We successfully demonstrated micro-patterning on chip using the situ uv-crosslinking of hydrogels to establish cell-barriers. Cell viability in the chip was tested by seeding and incubating iPSCs for two weeks. We confirmed that smNPCs and iPSCs can be differentiated into neurons and form self-assembled clusters with high interconnectivity when seeded in Hydrogel. Moreover, mesh microelectrode arrays (MEAs) are integrated into microfluidic chips. The established system is promising to record the electrophysiological activity of neurons. This project offers a promising Brain Organoid-on-Chip platform for better understanding brain development. This work has the potential to transform the field and have many applications especially for studying neurodevelopmental disorders.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз