Blood Brain Barrier in a Dish
Jacqueline Van Siclen
Department of Biology
Faculty Supervisor: Lily Chen
The development of the human blood brain barrier is a complex process that is not easily recapitulated in animals. Neurovascular cellular crosstalk is vital for healthy development, and when it is disrupted developmental delays may occur. Babies born before 26 weeks often experience hypoxia in the neonatal intensive care unit and moderate to severe neurodevelopmental delay in childhood. Much of the complexity is caused by cross-talk between several cell types, including endothelial tip cells, which leads vessel sprouting. Tip cells also secrete adrenomedullin (ADM), which promotes cell cycling of neural progenitors to create the large cellular mass that is necessary in human cortical development, while neural cells secrete ligands to promote a more specific brain vessel identity. Several models have been built in order to better understand how development is disrupted in preterm birth. One such model is the vaso-cortical assembloid model, which combines vascular and cortical organoids to model blood brain barrier development. While promising, there is much optimization and analysis to be done. This includes determining the timing of vascular and cortical organoids and methods of fusion. Additionally, it must be determined how the vessels meet and create a mature blood vessel. This work aims to elucidate these developmental hallmarks and further validate the system using it to screen for ADM as a possible therapeutic for hypoxia, enabling the vaso-cortical assembloid model as a vital tool in understanding human development and screen therapeutics.