Murine bone marrow stromal cell culture with features of mesenchymal stem cells susceptible to mouse-adapted human TSE agent, Fukuoka-1.

ABSTRACT

Transmission of transmissible spongiform encephalopathies (TSEs)/prion diseases through transplantation of bone marrow (BM) has never been reported in humans. However, the use of fetal bovine serum in current protocols for generating mesenchymal stem cells (MSCs) carries the risk of iatrogenic spread. We developed a cell model from murine BM-derived MSCs and tested its susceptibility to Fukuoka-1 (Fu) strain of TSEs. The adherent cells expressed significant levels of normal prion protein, PrPC, at the time when they became immortalized. The cell culture underwent spontaneous transformation following inoculation with Fu-infected brain homogenate and became persistently infected after reinoculation with Fu agent. Extensive analysis of the original and two Fu-exposed cell cultures revealed a phenotype characteristic of MSCs with a majority of cells being positive for stem cell antigen, Sca-1. Taken together, our results demonstrate that BM-derived MSCs can be infected with TSE agents under certain conditions ex vivo. Comprehensive studies should be undertaken to address the safety of cell-based therapies in regard to iatrogenic transmission of TSEs. BM-derived cell cultures can be used for studies of molecular mechanisms underlying the cells' susceptibility to various strains of TSEs, their propagation ex vivo, and for screening of potential anti-TSEs therapeutics.