Category: Assay Development and Screening
There is a significant need for in vitro systems that more closely model the human nervous system and its response to environmental toxins. Such a platform would have greater predictive power to indicate which compounds pose a risk. Toward this goal, we have developed a platform centered on the use of iPSC-derived human neurons. First, iPSCs were gene-edited to ubiquitously express eGFP. We then patterned these iPSCs to a neuroepithelial fate and next to neuronal progenitors before finally differentiating them into neurons. Spinal motor neurons were generated in this manner and used for this proof-of-concept project. They were plated in 384-well format for high-content imaging. Optimizing imaging in this manner required attention to the source of cells, plate surface coating, medium composition, staining protocol, imaging parameters, and the timeline for neuron maturation and neurite outgrowth. Refinement of all parameters yielded a sensitive and robust system with a Z-prime value greater than 0.5.
Michael Hendrickson– Project Manager, BrainXell, Inc., Madison, WI
Mr. Hendrickson has worked for over a dozen years in the biotech industry, half of which in CNS drug development. He has an extensive background in neuroscience and advanced fluorescence microscopy. He works with BrainXell's collaborators on a range of projects that employee the company's iPSC-derived human neurons. In addition, he oversees BrainXell's internal drug discovery efforts for SMA and ALS using a human motor neuron platform.