No abstract

We present a microfluidic vascular device. Vascular cells in a 3D-ECM environment support hemodynamic flow and enable monocyte interaction.

CIPN), which is rapidly induced after the administration of anti-cancer drugs (Argyriou et al., 2012; Cavaletti and Marmiroli, 2010). Patients with CIPN may experience a range of sensory symptoms including spontaneous tingling, burning pain, and joint and muscle pain in the distal extremities in a "glove and stocking" distribution (Peters et al., 2007). Often, these side effects discourage patient use of the drug, leading to delays or limited dosages and even discontinued treatment altogether (Staff et al., 2017). In some patients, these symptoms resolve following discontinuation of therapy, but an estimated 30% of patients are left with permanent symptoms that affect their overall quality of life (Rivera and Cianfrocca, 2015). Drugs with neurotoxic side effects reaching market approval is attributed to a lack of reliable screens for drug candidate neurotoxicity.Traditional methods for studying neuronal damage and screening neurotoxicity have largely relied on cell and animal models

Stroke is a devastating neurological disorder and a leading cause of death and long-term disability. Despite many decades of research, there are still very few therapeutic options for patients suffering from stroke or its consequences. This is partially due to the limitations of current research models, including traditional in vitro models which lack the three-dimensional (3D) architecture and cellular make-up of the in vivo brain. 3D spheroids derived from primary postnatal rat cortex provide an in vivo-relevant model containing a similar cellular composition to the native cortex and a cell-synthesized extracellular matrix. These spheroids are cost-effective, highly reproducible, and can be produced in a high-throughput manner, making this model an ideal candidate for screening potential therapeutics. To study the cellular and molecular mechanisms of stroke in this model, spheroids were deprived of glucose, oxygen, or both oxygen and glucose for 24 hours. Both oxygen and oxygen-glucose deprived spheroids demonstrated many of the hallmarks of stroke, including a decrease in metabolism, an increase in neural dysfunction, and an increase in reactive astrocytes. Pretreatment of spheroids with the antioxidant agent N-acetylcysteine (NAC) mitigated the decrease in ATP seen after 24 hours of oxygen-glucose deprivation. Together, these results show the utility of our 3D cortical spheroid model for studying ischemic injury and its potential for screening stroke therapeutics.