Using human cortical and cerebral organoids to model prenatal hypoxic-ischemic encephalopathy
Faculty Sponsor
Jenny Hsieh
Session Type
Poster Presentation
Research Project Abstract
Hypoxic-ischemic encephalopathy, or HIE, is damage to the brain caused by oxygen deprivation. Damage will manifest as neuronal cell stress and cell death, followed by an equally damaging inflammatory response in the brain. HIE due to neonatal asphyxia is a leading cause of mortality and severe impairment among infants, and can result in epilepsy, motor impairment, and a wide range of neurological deficits. Unfortunately, therapies for HIE are limited, as it’s been difficult to create functional models for prenatal hypoxia. This project examines the use of organoids derived from human embryonic stem cells as a potential disease model for HIE. In organoid models, cell death and subsequent upregulation of astrocytes in hypoxic conditions would support the use of organoids as a model for this encephalopathy. By growing cerebral and cortical organoids and subjecting them to varying degrees of hypoxia, followed by immunohistochemistry, we could determine qualitative levels of cell death and cell stress in organoid tissues. Our results suggest that cerebral and cortical organoids could potentially be used as a model for prenatal hypoxia and hypoxic-ischemic encephalopathy, from which new treatments could be derived. Cell damage and upregulation of surrounding astrocytes under chronic hypoxic conditions reflects cell damage seen in HIE. However, the effect of acute hypoxic conditions on organoid tissues do not show qualitative differences from control groups, suggesting that organoids may be an ineffective model for acute fetal hypoxic-ischemia.
Session Number
PS1
Location
HUB Multipurpose Room
Abstract Number
PS1-x
Using human cortical and cerebral organoids to model prenatal hypoxic-ischemic encephalopathy
HUB Multipurpose Room
Hypoxic-ischemic encephalopathy, or HIE, is damage to the brain caused by oxygen deprivation. Damage will manifest as neuronal cell stress and cell death, followed by an equally damaging inflammatory response in the brain. HIE due to neonatal asphyxia is a leading cause of mortality and severe impairment among infants, and can result in epilepsy, motor impairment, and a wide range of neurological deficits. Unfortunately, therapies for HIE are limited, as it’s been difficult to create functional models for prenatal hypoxia. This project examines the use of organoids derived from human embryonic stem cells as a potential disease model for HIE. In organoid models, cell death and subsequent upregulation of astrocytes in hypoxic conditions would support the use of organoids as a model for this encephalopathy. By growing cerebral and cortical organoids and subjecting them to varying degrees of hypoxia, followed by immunohistochemistry, we could determine qualitative levels of cell death and cell stress in organoid tissues. Our results suggest that cerebral and cortical organoids could potentially be used as a model for prenatal hypoxia and hypoxic-ischemic encephalopathy, from which new treatments could be derived. Cell damage and upregulation of surrounding astrocytes under chronic hypoxic conditions reflects cell damage seen in HIE. However, the effect of acute hypoxic conditions on organoid tissues do not show qualitative differences from control groups, suggesting that organoids may be an ineffective model for acute fetal hypoxic-ischemia.
