Background: The olfactory neuroepithelium contains neural stem cells which undergo continual neurogenesis and tissue regeneration. We investigated whether intrastriatal transplantation of human olfactory neuroepithelial cells (ONECs) can rescue the striatal pathology in a transgenic model of Huntington’s disease (HD).
Methods: Human ONECs were cultured from nasal endoscopic biopsy specimens of healthy volunteers, and induced into neurosphere-forming cells. In R6/2 transgenic mice, ONECs (0.5 million cells, R6/2-ONEC) or saline (R6/2-control) were transplanted into each bilateral striatum at age of 5 or 8 weeks. We measured Rotarod performance, body weights, and limb clasping score twice every week, and checked the survivals of the mice. Striatal atrophy and ubiquitin-positive nuclear aggregates, as well as the differentiations of transplanted ONECs were measured by stereologic methods at the age of 12 weeks.
Results: ONEC transplantation improved Rotarod performance, and attenuated limb clasping phenomenon of R6/2 mice from 8 to 12 weeks of the age. The R6/2-ONEC mice showed expanded survival lengths compared to the R6/2-control mice. Striatal neuronal loss and ubiquitin-positive huntingtin aggregation were all decreased in the R6/2-ONEC mice. Transplantation of ONECs at the earlier age (5 weeks) showed no difference in the efficacies compared to the transplantation at 8 weeks. Transplanted cells expressed Nestin, Tuj-1, GABA and GAD, although they showed limited migratory patterns and low cell survivals.
Conclusion: Our data suggest that ONEC is a feasible cell source for the future cell transplantation therapy for HD patients.