Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Evidence for Microchimerism in Baboon Recipients of Pig Hearts

Hina Jhelum
,
Martin Bender
ORCID logo ,
Bruno Reichart
,
Maren Mokelke
,
Julia Radan
,
Elisabeth Neumann
,
Ludwig Krabben
,
Jan-Michael Abicht
,
Benedikt Kaufer
,
Matthias Längin
,
Joachim Denner
* ORCID logo
Version 1 : Received: 23 June 2023 / Approved: 26 June 2023 / Online: 26 June 2023 (09:30:58 CEST)

A peer-reviewed article of this Preprint also exists.

Jhelum, H.; Bender, M.; Reichart, B.; Mokelke, M.; Radan, J.; Neumann, E.; Krabben, L.; Abicht, J.-M.; Kaufer, B.; Längin, M.; Denner, J. Evidence for Microchimerism in Baboon Recipients of Pig Hearts. Viruses 2023, 15, 1618. Jhelum, H.; Bender, M.; Reichart, B.; Mokelke, M.; Radan, J.; Neumann, E.; Krabben, L.; Abicht, J.-M.; Kaufer, B.; Längin, M.; Denner, J. Evidence for Microchimerism in Baboon Recipients of Pig Hearts. Viruses 2023, 15, 1618.

Abstract

Xenotransplantation is, like allotransplantation, usually associated with microchimerism, e.g., 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 non-human 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. That makes it difficult to discriminate between microchimerism and PERV infection of the recipient. Here, we demonstrate which virological methods should be used to identify microchimerism, first of all screening for porcine cellular genes. Using porcine short interspersed nuclear sequences (SINES), which have hundred 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. Finally, 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 in all animals. These methods can be used in future clinical trials.

Keywords

xenotransplantation; porcine endogenous retroviruses; microchimerism; pig genes; SINE

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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