Gayosso, L. 1 , López de Maturana, R. 2 , Giorgetti, A. 3 , López de Munain, A. 4 , Castilla, J. 1 & Sánchez-Pernaute, R. 2
1 Centro de Investigación Cooperativa en biociencias CiCbioGUNE, Bilbao
2 Centro de Investigación en medicina regenerativa Inbiomed, San Sebástian
3 Fundación Carreras, Barcelona
4 Instituto de investigación sanitaria Biodonostia, San Sebastián
Transmissible Spongiform Diseases that affect animal and humans are fatal neurodegenerative diseases for which there is no available therapy. Creutzfeldt - Jakob Disease, Fatal Familial Insomnia and the Gerstmann-Sträussler-Schinker affect humans. These diseases can be sporadic, hereditary or infectious, present long incubation periods with no clinical signs or symptoms. The pathogenic agent is the Prion Protein (PrPSc) and is normal form is the cellular protein (PrPc).
It has been possible to replicate prions in cell cultures that overexpress murine or ovine PrPc, indicating that the replication capacity of prions depends partly on the expression levels of endogenous PrPc and on the sequence identity between prion and PrPc expressed into the cells. In the current study we aim to establish a human in vitro cellular model able to support replication of human prions taking advantage of cell reprogramming technology. We have characterized the temporal profile of PrPc expression in human neurons derived from pluripotent stem cells and induced neurons obtained through direct transdifferentiation from human fibroblast; noticing a good PrPc expression levels in both kinds of neurons at different days confirming a robust expression from div 20 onwards. Therefore, the cellular model will be useful both for mechanistic and therapeutic studies.