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 HaverichAnn Transplant 2002; 7(3): 40-45 :: ID: 5541
Abstract
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.
Most Viewed Current Articles
15 Aug 2023 : Review article 7,203
Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ TransplantationDOI :10.12659/AOT.939750
Ann Transplant 2023; 28:e939750
03 Jan 2023 : Original article 7,086
Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and...DOI :10.12659/AOT.938467
Ann Transplant 2023; 28:e938467
16 May 2023 : Original article 6,914
Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections ...DOI :10.12659/AOT.939258
Ann Transplant 2023; 28:e939258
28 May 2024 : Original article 6,394
Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflura...DOI :10.12659/AOT.943281
Ann Transplant 2024; 29:e943281