06 December 2003
Induction of long-term peripheral microchimerism in non-human primates in a model of xenogeneic peripheral tolerance induction.A R Simon, C Schröder, U Martin, R Tessmann, C Templin, G Laaf, K Wiebe, G Steinhoff, B Lapin, M Chikobava, A Haverich
Ann Transplant 2002; 7(3): 40-45 :: ID: 5541
Xenotransplantation represents a promising solution to the ever increasing shortage of donor organs in allotransplantation. However, due to different and stronger modes of rejection, successful xenotransplantation will require different organ-protective regimes from those used in allogeneic transplantation today. Since one can not simply increase the dosage of the drugs used, immunomodulation or tolerance induction of the recipient would be the most desirable approach. Transfusion of donor leukocytes has been shown to downregulate recipient responses or even induce peripheral tolerance in small animal models. Since the infusion of donor cells represents a relatively simple approach, as one can purify and compose the inoculum exactly before infusion, we studied whether this approach can be successfully employed in a preclinical swine to non-human primate model of peripheral tolerance induction/immunomodulation. In our model, baboons underwent sequential column adsorption and complement blockade. The animals received only initial immunosuppression with cyclophosphamide. No further immunosuppression was given. Subsequently all animals received 1-3 x 10(10) porcine splenocytes i.v. Development and maintenance of chimerism was analyzed by sequential flow cytometric and PCR analyses. Other parameters studied included effects of the preparatory induction protocol. We could show that a low level of chimerism is maintained in these animals for up to 1.5 years, despite the fact that they received no additional immunosuppression after the initial one. At no time of the experiment did any animal display symptoms of poor health. Thus we demonstrate that the concept of donor leukocyte transfusion is transferable into preclinical xenotransplantation. We are currently conducting organ transplantation experiments into animals thus treated to directly analyze the immunomodulatory effect of the donor cells.
12 Feb 2024 : Original articleNo Prognostic Impact of Graft-to-Recipient Weight Ratio on Hepatocellular Carcinoma Recurrence Following Li...
Ann Transplant In Press; DOI: 10.12659/AOT.942767
Most Viewed Current Articles
05 Apr 2022 : Original articleImpact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver Transplantation
Ann Transplant 2022; 27:e935604
12 Jan 2022 : Original articleRisk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...
Ann Transplant 2022; 27:e934738
22 Nov 2022 : Original articleLong-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...
Ann Transplant 2022; 27:e937988