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A 3D hiPSC cortical tissue model for quantifying the effects of galactic cosmic radiation on functional cortical networks

Active TRL 2 (started at 2, targeting 3)

Description

Chronic galactic cosmic radiation (GCR) exposure represents a major health concern for astronauts and a barrier to crewed missions outside of low earth orbit. This proposal aims to develop a 3D human cortical tissue model (CTM) for studying GCR exposure effects and screening potential pharmacological preventions and countermeasures. I will design and build a 3D hiPSC-based CTM by optimizing the structural, physical, biological, and phenotypic characteristics of human cortical tissue to support short-to-long- term investigation of GCR in ‘healthy’ tissue. Once established, the CTM will be exposed to a proton beam at the UMass Lowell Radiation Laboratory facilities, in accordance with the dose identified by NASA as the permissible exposure limit for astronauts’ central nervous system. CTMs and mouse organotypic cortical slice cultures (mOCs) will be treated with and without radioprotective compounds before proton treatment. Changes to cellular homeostasis and function will be quantified by measuring cell death, reactive oxygen species, secreted stress markers, and electrical activity at 2-day intervals. Additionally, DNA damage and cellular morphology will be quantified by immunocytochemistry at the terminal time point. After the investigation of CTM response to proton beam exposure, CTMs and mOCs will then be treated with ionizing protons or simulated GCR, which mimics radiation conditions beyond low earth orbit. Simulated GCR and ionizing proton treatment will occur at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Differential damage to CTMs and mouse organotypic cortical slices between proton and simulated GCR treated samples will be evaluated using the above mentioned biological readouts. This platform represents an essential tool for improving our understanding of radiation neurobiology at the cellular, network, and tissue levels. It will be instrumental in the development of countermeasures to combat acute and long-term neurodegenerative effects of GCR during crewed space flights.

Details

Technology areaHuman Health, Life Support, and Habitation Systems > Radiation > Radiation Mitigation and Biological Countermeasures
ProgramSpace Technology Research Grants (STRG)
Lead organizationUniversity of Massachusetts-Lowell, Lowell, MA
Start date2023-08-29
End date2027-08-28

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