Compartmentalized Devices as Tools for Investigation of Human Brain Network Dynamics

Abstract

Neuropsychiatric disorders have traditionally been difficult to study due to the complexity of the human brain and limited availability of human tissue. Induced pluripotent stem (iPS) cells provide a promising avenue to further our understanding of human disease mechanisms, but traditional 2D cell cultures can only provide a limited view of the neural circuits. To better model complex brain neurocircuitry, compartmentalized culturing systems and 3D organoids have been developed. Early compartmentalized devices demonstrated how neuronal cell bodies can be isolated both physically and chemically from neurites. Soft lithographic approaches have advanced this approach and offer the tools to construct novel model platforms, enabling circuit-level studies of disease, which can accelerate mechanistic studies and drug candidate screening. In this review, we describe some of the common technologies used to develop such systems and discuss how these lithographic techniques have been utilized to advance our understanding of neuropsychiatric disease. Finally, we address other in vitro model platforms such as 3D culture systems and organoids and compare these models with compartmentalized models and ask important questions regarding how we can further harness induced pluripotent stem cells in these engineered culture systems for the development of improved in vitro models. This article is protected by copyright. All rights reserved.

Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications

“…In recent years, and especially in the last decade, stem cell research has blossomed into an exciting and promising field. Stem cells, especially ESCs and iPSCs have shown great application promise in four major fields: regenerative and transplant medicine [11,12]; disease modeling [13,14]; drug discovery screening [15,16]; and human developmental biology [17] [18],. Thus, the evolution of regenerative medicine continues, from the early first descriptions of stem cells to their expanding clinical applications at present.…”

Development of a high-throughput arrayed neural circuitry platform using human induced neurons for drug screening applications

“…One advantage of compartmentalized devices is to unbalance the liquid heights between compartments so that individual chambers can be treated with distinct chemicals without diffusion between chambers. 5,6 Creation of a thicker PDMS insert into the microplate would extend the wall between compartments, allowing these individual treatments. To facilitate automation in the image processing of neural activity data, the incorporation of an automated ROI tracer should be explored in future work.…”

“…Recently, microfabrication has presented itself as a major tool for generating compartmentalized neural circuit models, many of which utilize a design and fabrication approach similar to that originally developed by the Jeon group [2][3][4][5][6] in which connecting microchannels between compartments facilitate axonal extension while preventing cell body migration between adjacent chambers. While these compartmentalized devices were initially designed for modeling axonal injury, they demonstrated the utility of microfabrication to create similar devices for neuronal communication studies.…”

Compartmentalized Neuronal Culture for Viral Transport Research

“…It is difficult to manipulate and control the axonal growth of neurons in tissue culture plates with isotropic environment because establishment of neuronal polarity involves spontaneous and randomly orientated outgrowth. Compartmentalized culture systems confer a major advantage over single-chamber cell cultures by spatially separating the cellular compartment, the soma, and extension of the axon (Atencia and Beebe, 2005 ; Fantuzzo et al, 2019 ).…”