Evidence for Microchimerism in Baboon Recipients of Pig Hearts

Author:

Jhelum Hina1,Bender Martin2ORCID,Reichart Bruno3,Mokelke Maren4,Radan Julia4,Neumann Elisabeth4,Krabben Ludwig1,Abicht Jan-Michael2,Kaufer Benedikt1ORCID,Längin Matthias2ORCID,Denner Joachim1ORCID

Affiliation:

1. Institut of Virology, Free University Berlin, 14163 Berlin, Germany

2. Department of Anaesthesiology, University Hospital, LMU Munich, 81377 Munich, Germany

3. Transregional Collaborative Research Center 127, Walter Brendel Centre of Experimental Medicine, LMU Munich, 81377 Munich, Germany

4. Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany

Abstract

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.

Funder

Deutsche Forschungsgemeinschaft

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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