title: Characterization of mesenchymal stem cells in  sheep naturally infected with scrapie.
abstract: Mesenchymal stem cells (MSCs) can be infected with prions and have been proposed as in vitro cell-based models for prion replication. In addition, autologous MSCs are of interest for cell therapy in neurodegenerative diseases. To the best of our knowledge, the effect of prion diseases on the characteristics of these cells has never been investigated. Here, we analysed the properties of MSCs obtained from bone marrow (BM-MSCs) and peripheral blood (PB-MSCs) of sheep naturally infected with scrapie — a large mammal model for the study of prion diseases. After three passages of expansion, MSCs derived from scrapie animals displayed similar adipogenic, chondrogenic and osteogenic differentiation ability as cells from healthy controls, although a subtle decrease in the proliferation potential was observed. Exceptionally, mesenchymal markers such as CD29 were significantly upregulated at the transcript level compared with controls. Scrapie MSCs were able to transdifferentiate into neuron-like cells, but displayed lower levels of neurogenic markers at basal conditions, which could limit this potential .The expression levels of cellular prion protein (PrPC) were highly variable between cultures, and no significant differences were observed between control and scrapie-derived MSCs. However, during neurogenic differentiation the expression of PrPC was upregulated in MSCs. This characteristic could be useful for developing in vitro models for prion replication. Despite the infectivity reported for MSCs obtained from scrapie-infected mice and Creutzfeldt–Jakob disease patients, protein misfolding cyclic amplification did not detect PrPSc in BM- or PB-MSCs from scrapie-infected sheep, which limits their use for in vivo diagnosis for scrapie.
authors.affiliation: Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Diego R
authors.initials: DR
authors.lastname: Mediano
authors.affiliation: Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sanz-Rubio
authors.affiliation: Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bolea
authors.affiliation: Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Marín
authors.affiliation: Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Vázquez
authors.affiliation: Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Remacha
authors.affiliation: Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.|Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: López-Pérez
authors.affiliation: CIC bioGUNE, Parque Tecnológico de Bizkaia, Derio, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Fernández-Borges
authors.affiliation: CIC bioGUNE, Parque Tecnológico de Bizkaia, Derio, Spain.|IKERBasque, Basque Foundation for Science, Bilbao, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Castilla
authors.affiliation: Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Zaragoza
authors.affiliation: Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badiola
authors.affiliation: Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Clementina
authors.initials: C
authors.lastname: Rodellar
authors.affiliation: Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.|Laboratorio de Genética Bioquímica, Instituto de Investigación Agroalimentaria (IA2), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Martín-Burriel
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D022081:Cell Surface Extensions / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D012608:Scrapie / Q000473:pathology*; D012756:Sheep