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    Evidence for microchimerism in baboon recipients of pig hearts (2023)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Jhelum, Hina (WE 5)
    Bender, Martin
    Reichart, Bruno
    Mokelke, Maren
    Radan, Julia
    Neumann, Elisabeth
    Krabben, Ludwig (WE 5)
    Abicht, Jan-Michael
    Kaufer, Benedikt (WE 5)
    Längin, Matthias
    Denner, Joachim (WE 5)
    Quelle
    Viruses
    Bandzählung: 15
    Heftzählung: 7
    Seiten: Artikel 1618
    ISSN: 1999-4915
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://www.mdpi.com/1999-4915/15/7/1618
    DOI: 10.3390/v15071618
    Pubmed: 37515304
    Kontakt
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    14163 Berlin
    +49 30 838 51833
    virologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Xenotransplantation, like allotransplantation, is usually associated with microchimerism, i.e., the presence of cells from the donor in the recipient. Microchimerism was reported in first xenotransplantation trials in humans, as well as in most preclinical trials in nonhuman primates (for review, see Denner, Viruses 2023, 15, 190). When using pigs as xenotransplantation donors, their cells contain porcine endogenous retroviruses (PERVs) in their genome. This makes it difficult to discriminate between microchimerism and PERV infection of the recipient. Here, we demonstrate the appropriate virological methods to be used for the identification of microchimerism, first by screening for porcine cellular genes, and then how to detect infection of the host. Using porcine short interspersed nuclear sequences (SINEs), which have hundreds of thousands of copies in the pig genome, significantly increased the sensitivity of the screening for pig cells. Second, absence of PERV RNA demonstrated an absence of viral genomic RNA or expression as mRNA. Lastly, absence of antibodies against PERV proteins conclusively demonstrated an absence of a PERV infection. When applying these methods for analyzing baboons after pig heart transplantation, microchimerism could be demonstrated and infection excluded in all animals. These methods can be used in future clinical trials.