A Microfluidic Device to Study the Neurovascular Niche

Presenter: Max Winkelman

Research Category: Physical and LIfe Sciences
Additional Authors: Guohao Dai

Neural progenitor cells (NPCs) possess the abilities to self-renew and differentiate into neurons, making them potential therapeutics for neurodegenerative diseases. However, when studied in 2D cell culture, human NPCs exhibit limited self-renewal and differentiation capacity, hindering stem cell research. In the adult human brain, self-renewing NPCs are exclusively found in close proximity to microvascular networks in microenvironments called neurovascular niches (NVNs). These niches are composed of brain endothelial cells, pericytes, and astrocytes, which provide paracrine and juxtacrine signals that govern NPC self-renewal and differentiation. Our overarching goal is to replicate features of the NVN in vitro to elucidate the influences of NPC self-renewal and differentiation. To accomplish this, we utilized commercial microfluidic devices (MFDs) to develop 3D perfused microvascular networks that physiologically mimic the NVN. These MFDs can generate interstitial flow, which promoted blood vessel anastomosis and increased vessel area and diameter compared to the condition without interstitial flow. We hypothesized that human NPCs co-cultured with microvascular networks would exhibit enhanced self-renewal and reduced differentiation to neurons compared to NPC monoculture. This will be confirmed by measuring NPC expression of stem cell markers (SOX2 and Nestin) and neurite characteristics (density and length), respectively. Moving forward, we will modify experimental parameters (cell heterogeneity, extracellular matrix composition, and luminal flow) and observe the effect on NPC behavior (self-renewal, differentiation, proliferation, and spatiotemporal organization). This MFD serves as a physiologically relevant model and will advance translational research regarding NPC fate and their future application towards neurodegenerative diseases.