Harnessing Vascular Stem Cells to Grow Brain Organoids
By: Janeth Ochoa Birrueta
Department: Biology
Faculty Advisor: Dr. Lily Chen
Brain organoids are three dimensional models derived from stem cells that self-assemble into an organized structure given the right environment and conditions. However, despite the rapid advancements in stem cell technology the current brain organoid models are limited in their growth, development and survival. In addition to traditional views of vasculature as delivering oxygen and nutrients, recent studies have suggested that the vasculature of the brain plays a vital role in development by regulating neuronal differentiation and migration. Therefore, understanding these neurovascular interactions is critical in understanding how the vasculature is formed in the developing brain. By understanding these neurovascular interactions, we can then begin to build a vasculature network in brain organoids. To emulate these interactions, we have created tricellular, “Neurovascular Units” (NVU) with primary neural, endothelial, and mural cells purified from human brain samples with fluorescence-activated cell sorting (FACS). These NVUs can be maintained in culture for up to 5 weeks. Furthermore, endothelial cells form tubes in these NVUs and mural cells appropriately localize on top of the endothelial tube. After 5 weeks in culture, neural cells in these organoids give rise to astrocytes, inhibitory neurons, layer 2/3 and layer 5/6 neurons. Comparing NVUs with assembloids of neural cells only, vascular cells promote the maintenance of progenitor cells over differentiated cells, as has been shown in vivo with mouse neural stem cells. In conclusion, primary vascular and neural cells form robust assembloids that accurately replicate some aspects of in vivo neurovascular interactions.