Human Neural Cell-Based Biosensor.

摘要

Human neural cell types derived from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) have a strong potential for use as cell-based biosensors for environmental toxins. Here, we report the following accomplishments in developing a neural cell-based biosensor. (1) We have developed methods to differentiate hESC-derived neural progenitor cells to dopaminergic-like neurons, allowing us to create a more physiologically relevant, HTS-ready in vitro model for Parkinson s disease research. (2) We have translated this dopaminergic differentiation methodology to hiPSC-derived neural progenitor cells. (3) As result of our dopaminergic differentiation studies, we have generated a unique, first-of-its-kind human dopaminergic progenitor cell that we are developing for commercial release. (4) We have developed methods to differentiate hESC-derived neural progenitor cells into astrocytes. (5) We have translated this astrocyte differentiation methodology to hiPSC-derived neural progenitor cells. (6) We have continued development of a fluorescence based, high content imaging (HCI) assay for neurogenesis with the potential as either a single or multiplexed assay format to identify compounds with effects on proliferation, differentiation and neurite outgrowth to delineate mechanism-of-action for unknown neurotoxicants. (7) We have begun development of an improved cellular model system and neuromuscular junction bioassay for the detection and counteraction of botulinum neurotoxin poisoning. (8) The progress we have made has led to other successful grant applications and new and better ArunA product line development.