Fukuoka-1 strain of transmissible spongiform encephalopathy agent infects murine bone marrow-derived cells with features of mesenchymal stem cells

BACKGROUND: The possible risk of iatrogenic transmissible spongiform encephalopathies (TSEs, prion diseases) from transplantation of marrow-derived mesenchymal stem cells (MSCs) is uncertain. While most cell lines resist infection, a few propagate TSE agents. STUDY DESIGN AND METHODS: We generated MSC-like (MSC-L) cell cultures from bone marrow (BM) of mice inoculated with the human-derived Fukuoka-1 (Fu) strain of TSE agent. Cultured cells were characterized for various markers and cellular prion protein (PrP^C) by fluorescence-activated cell sorting and for PrP^C and its pathologic TSE-associated form (PrP^TSE) by Western blotting (WB). Cell cultures were tested for their susceptibility to infection with Fu in vitro. The infectivity of one Fu-infected cell culture was assayed in mice. RESULTS: BM cells from Fu-infected mice expressed neither PrP^C nor PrP^TSE after 3 days in culture as demonstrated by WB. Cells adherent to plastic and maintained under two different culture conditions became spontaneously immortalized and began to express PrP^C at about the same time. One culture became transformed shortly after exposure to Fu in vitro and remained persistently infected, continuously generating PrP^TSE through multiple passages; the infectivity of cultured cells was confirmed by intracerebral inoculation of lysates into mice. Both persistently TSE-infected and uninfected cells expressed a number of typical MSC markers. CONCLUSION: BM-derived MSC-L cells of mice became persistently infected with the Fu agent under certain conditions in culture-conditions that differ substantially from those currently used to develop investigational human stem cell therapies.