Abstract: Treating neurological diseases and disorders accounts for 6.7% of the total attributable cost of illness in Canada. These issues arise when healthy neural tissue stops functioning properly. My research focuses on developing personalized engineered tissues that could successfully provide a long term strategy for treating diseases and disorders of the central nervous system, such as spinal cord injury. We hypothesized that generating spinal motor neurons (sMNs) from human induced pluripotent stem cells (hiPSCs)-derived neural aggregates (NAs) using a chemically-defined differentiation protocol would be more effective inside of 3D fibrin hydrogels compared to 2D laminin-coated surfaces. To test this hypothesis, we performed targeted RNA-Seq using next generation sequencing to determine the substrate-specific genetic differences that regulate cell phenotype. Cells cultured on both substrates expressed sMN genes CHAT and MNX1, though persistent Wnt signaling contributed to a higher proportion of interneurons in NAs cultured in 3D fibrin scaffolds. Cells in fibrin also expressed lower levels of astrocyte progenitor genes and higher levels of the neuronal-specific gene TUBB3, suggesting a purer population of neurons compared to the 2D cultures. This work provides insight into how fibrin hydrogels affect neuronal induction and these insights can then be used to tailor the properties of these hydrogels to optimize sMN generation for regenerative medicine applications.

Biography: Dr. Willerth holds a Canada Research Chair in Biomedical Engineering at the University of Victoria where she holds dual appointments in the Department of Mechanical Engineering and the Division of Medical Sciences as an Associate Professor. Her honors include being a 2015 Young Innovator in Cellular and Biological Engineering and being named a "Star in Global Health" by Grand Challenges Canada in 2014.  She is currently on sabbatical at the Wisconsin Institute for Discovery supported by the International Collaboration on Repair Discoveries International Travel Award.

~BME Faculty Host: Craig Goergen~

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