Compartmentalized Devices as Tools for Investigation of Human Brain Network Dynamics

• Published in: Developmental dynamics Vol. 248; no. 1; pp. 65 - 77
• Main Authors: Fantuzzo, Joseph A., Hart, Ronald P., Zahn, Jeffrey D., Pang, Zhiping P.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2019
• Subjects: 3D culture; Animals; axonal transport; Axons; Brain; Brain - anatomy & histology; Cell Compartmentation; Cell culture; Cell Culture Techniques - methods; compartmentalization; Complexity; Disease control; Humans; Huntington's Disease; induced neurons; Induced Pluripotent Stem Cells - cytology; Mental disorders; microfluidics; Models, Biological; Neural networks; neurocircuitry; Neurons; neuropsychiatric disorders; Organic chemistry; Organoids; Organoids - cytology; Organoids - innervation; Platforms; Pluripotency; Printing, Three-Dimensional; stem cells; Three dimensional models; stem cells; 3D culture; Huntington's Disease; compartmentalization; organoids; axonal transport; neuropsychiatric disorders; neurocircuitry; microfluidics; induced neurons
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.24665

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 used 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. We ask important questions regarding how we can further harness iPS cells in these engineered culture systems for the development of improved in vitro models. Developmental Dynamics 248:65–77, 2019. © 2018 Wiley Periodicals, Inc. Key Findings Compartmentalization segregates neuronal cell bodies from neurites. Most devices to date have been used to demonstrate the principal of compartmentalization in circuit dynamics. Devices need to focus design toward capturing disease‐specific features. Incorporation of stem cell‐derived neurons with devices can link circuit dynamics to human‐specific disease elements.