Fukuoka-1 strain of transmissible spongiform encephalopathy agent infects murine bone marrow–derived cells with features of mesenchymal stem cells
Corresponding Author
Larisa Cervenakova
Larisa Cervenakova, Transmissible Diseases Department, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855; e-mail: [email protected].Search for more papers by this authorSergey Akimov
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorIrina Vasilyeva
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorOksana Yakovleva
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorCarroll McKenzie
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorJuraj Cervenak
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorPedro Piccardo
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorDavid M. Asher
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorCorresponding Author
Larisa Cervenakova
Larisa Cervenakova, Transmissible Diseases Department, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855; e-mail: [email protected].Search for more papers by this authorSergey Akimov
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorIrina Vasilyeva
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorOksana Yakovleva
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorCarroll McKenzie
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorJuraj Cervenak
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorPedro Piccardo
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorDavid M. Asher
From the Transmissible Diseases Department, American Red Cross Holland Laboratory, Rockville, Maryland; the Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Kensington, Maryland; and the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Search for more papers by this authorSome cell culture studies were supported in part by an interagency transfer of funds to the FDA from NIAID, NIH.
The findings and conclusions in this article have not been formally disseminated by the FDA and should not be construed to represent any Agency determination or policy.
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.
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 (PrPC) by fluorescence-activated cell sorting and for PrPC and its pathologic TSE-associated form (PrPTSE) 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 PrPC nor PrPTSE 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 PrPC at about the same time. One culture became transformed shortly after exposure to Fu in vitro and remained persistently infected, continuously generating PrPTSE 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.
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