title: Fukuoka-1 strain of transmissible spongiform encephalopathy agent infects murine bone marrow-derived cells with features of mesenchymal stem cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, MD 20855, USA. cervenakl@usa.redcross.org
authors.forename: Larisa
authors.initials: L
authors.lastname: Cervenakova
authors.forename: Sergey
authors.initials: S
authors.lastname: Akimov
authors.forename: Irina
authors.initials: I
authors.lastname: Vasilyeva
authors.forename: Oksana
authors.initials: O
authors.lastname: Yakovleva
authors.forename: Carroll
authors.initials: C
authors.lastname: McKenzie
authors.forename: Juraj
authors.initials: J
authors.lastname: Cervenak
authors.forename: Pedro
authors.initials: P
authors.lastname: Piccardo
authors.forename: David M
authors.initials: DM
authors.lastname: Asher
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D008648:Mesoderm / Q000187:drug effects; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology* / Q000635:transmission; D011328:Prions / Q000378:metabolism / Q000472:pathogenicity* / Q000494:pharmacology / Q000502:physiology
chemical_list: D011328:Prions