Rapid functional characterization of patient-derived neural stem cells (360G-Wellcome-202445_Z_16_Z)

Human stem cells bring a great promise for personalized regenerative medicine, in vitro studies of patient-specific human diseases and new generation of effective drug-screening methods. In the last years, patient-derived induced pluripotent stem cells (iPSC) have been increasingly used in clinical trials of novel therapies and more fundamental studies on the genetic neuronal disorders. However, the great variability and heterogeneous behaviour of patient-derived iPSC lines has been recognized as a major obstacle in their clinical applications and in conclusive interpretation of in vitro studies and drug screening assays. Their functional electrical properties responsible for the neural function are particularly important for the success of neuroregenerative stem cell treatment. However, they are extremely difficult to study using traditional electrode-based methods and the selection of functionally optimal transplant cell line is currently unfeasible. In this project, we will apply our recently developed experimental system capable of rapid functional analysis of living neural cells to human iPSC-derived neurons. Using our light-based optogenetics approach we will aim to demonstrate an efficient methodology for selection of the optimal transplant iPSC line for neuroregenerative therapy based on its electrophysiological characteristics. Our non-invasive approach will enable complete electrophysiological characterization of hundreds of cells within each sample.