HUMAN INDUCED NEURAL STEM CELLS AS MODEL TO STUDY THE NEURAL DEVELOPMENT IN HUNTINGTON'S DISEASE

Background Induced pluripotent stem cell (iPSC) technology offers the possibility to generate patient-specific iPS cells and to enable the development of in vitro HD models that more accurately reflect the human disease. HD patients’ iPSC can be propagated indefinitely and differentiated into any cell type in the human body even functional neuronal cells, holding a great potential for disease modeling and drug screening. Aims 1) obtain neuronal cell lines starting from the patient’s fibroblasts using the iPSC technology 2) study the disease development 3) find compounds able to improve the HD phenotype. Methods Patient’s skin fibroblasts were reprogrammed into iPSCs through a virus-free protocol. All iPSC lines were characterized for their stemness and pluripotency, both in vitro through embryoid bodies formation and in vivo through teratoma formation assay. A protocol was optimized for iPCs neural differentiation (Rosati et al., under revision). We may obtain a neural population of astrocytes, oligodendrocytes. Results Fibroblasts obtained from two JHD patients, two adult HD patients and one healthy donor were reprogrammed into iPSC. iPSC neuralization has been performing to obtain neurosphere lines which will be analyzed at morphological and molecular level to underline functional and biochemical differences linked with the juvenile and adult Huntington’s disease. Conclusion NPCs were obtained from one JHD and a healthy donor. These ‘induced’ NPCs differentiated in three neural lineages: neurons, astroglia and oligodendrocytes. These cells can be studied for their morphological and functional characteristics to comprehend how the development of neural cells is impaired in Huntington’s disease.