Transplantation of organs is transplantations of donor DNA: fate of DNA disseminated in recipient

Abstract

Summary Microchimerism after allogeneic organ transplantation has been widely documented using DNA identification techniques. However, the question as to whether the detected donor DNA is present in the surviving donor passenger cells, recipient macrophages phagocytizing rejected donor cells, or dendritic cells (DC) internalizing donor apoptotic bodies or cell fragments has not been answered. We provide evidence that allogeneic organ transplantation is followed not only by cellular microchimerism caused by release of graft passenger cells but also dissemination of donor DNA from the ischemic rejecting graft cells and its internalization in recipient DC. The high levels of donor DNA at the time of heart rejection were inversely proportional to the concentration of donor passenger cells detected with use of flow cytometry. Depending on the type of graft, the kinetics of DNA distribution in recipient tissues were different. Immunosuppressive drugs attenuated the rejection reaction and release of DNA from grafts. Allogeneic but not syngeneic donor DNA fragments were found in recipient splenic DC‐enriched population. Interestingly, that donor DNA fragments could be detected in recipient tissue at high levels on day 30. This challenges the notion that fragments of DNA are immediately cleaved by cell plasmatic enzymes. The biologic significance of our findings is not clear. We speculate that donor DNA fragments in recipient DC may play a, so far unknown, role in the immunization/tolerance process to allogeneic antigens.

PCR-Based Methodology for Molecular Microchimerism Detection and Quantification

“…No flow cytometry was performed to identify which cells originate microchimerism. Moreover, microchimerism can also be a result of DNA contained in recipient cells or from apoptotic bodies as many authors have already published (45). Also, in unpublished data, we have performed a PCR directly from plasma to detect freedonor DNA in serum, but we did not obtain any positive result, leading us to the conclusion that microchimerism was originated by circulating cells or by DNA contained in recipient cells.…”

Gene Editing, the Mystic Threat to Human Dignity

“…5 In addition to being sick, do these people become undignified? The same happens in organ (Olszewski et al 2005) and bone narrow donations. 6 Both involve adding the donor's DNA to extracts of tissues from the recipient, but none of these situations diminishes the recipient's dignity.…”

Genetic analysis of allogenic donor cells after successful allo-limbal epithelial transplantation in simple and cultivated limbal epithelial transplantation procedures

“…Previous studies 28,29 have reported preliminary results that autologous conjunctival epithelial cell cultivated on amniotic membrane in a suitable environment can differentiate into the corneal epithelial phenotype and maintain a healthy ocular surface after transplantation in patients with total LSCD. Alternately, the circulating donor DNA of the graft cells may play a role in chimerism similar to solid organ transplantations, which was indicated in animal studies 30,31 and in one study of patients after kidney transplantation in whom the donor DNA was detected in recipient whole blood at 2 years postoperatively 32 .…”