Rosebrugh Bldg, Toronto, ON M5S 3G9
Room: RS 211
There has been interest in using stem cells of various origins to promote functional recovery in mammals following ischemic stroke. However, better tools are needed in order to investigate the mechanism by which stem cells are therapeutic following ischemic damage. We have previously shown that human neural precursor cells lead to functional recovery in a mouse model 32 days after ischemic stroke when transplanted 4 days post-injury into the glial scar region. Whether functional recovery is promoted by transplanted human neural precursor cells through cell replacement, or promoting host plasticity, is still unknown. In order to test how human neural precursor cells lead to functional recovery, we have developed specifically ablatable human neuroepithelial cells by engineering them to express the nitroreductase suicide gene. We show that our ablatable human neuroepithelial cells die specifically and in a dose dependant manner in response to metronidazole, which is metabolized selectively by nitroreductase leading to cell death. Upon observing functional recovery in mice that have received the ablatable human neuroepithelial cells post-stroke, we will ablate the transplant to observe whether recovery is retained or lost after ablation. Ultimately, understanding the therapeutic mechanisms of neural stem cell transplants for treating ischemic stroke will allow us to develop more fine-tuned cell based strategies to promote host repair after brain injury.