“Bioengineering CNS Morphogenesis for Scalable Application in Regulatory Science and Precision Medicine”

Hosted by the Department of Biomedical Engineering

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Abstract: Neural organoids derived from human pluripotent stem cells (hPSCs) are powerful tools for modeling and investigating CNS development, physiology, and disease. However, the innate and spontaneous emergent properties of neurally differentiating hPSC aggregates, which make neural organoids possible, also limits their application due to inconsistencies in the organoid’s cellular composition and tissue cytoarchitecture. We hypothesized that this was caused by the absence of biophysical and biochemical cues normally present within the developing embryo. To reinstate such controls in vitro, we developed culture methods and platforms that enable facile spatiotemporal control of such cues to result in a standardization of early neural organoid morphogenesis. In this talk, our success in exerting biophysical control over microscale tissue morphology to standardize the derivation of singularly polarized, forebrain through spinal neuroepithelial tissues and tubes will be presented. This mimics the earliest stage of CNS morphogenesis, i.e. neural tube formation. Additionally, scaling and application of this culture platform to provide an ‘off-the-shelf’ screen for quantitatively assessing the effects of chemicals, drugs, and genetic mutations on human brain and spinal cord will also be discussed.

Support for this work was funded by National Science Foundation CCF-1418976 & IIS-1447449 (RMW) and CBET-1651645 (RSA) grants, National Institute of Health 1U54 AI117924-01 (RMW), R21NS082618, R33NS082618, and R21HD103111 (RSA) grants, EPA STAR Award 83573701 (RSA), Burroughs Wellcome Fund Award 1014150 (RSA), and the Wisconsin Alumni Research Foundation through a Draper TIFF, Accelerator, and Fall Competition Awards.

Conflict of interest disclosure: RSA is a co-founder and interim CEO of Neurosetta LLC, which seeks to commercialize the presented technology.

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