Delayed non-myeloablative irradiation to induce long-term allograft acceptance in a large animal lung transplantation model
| Autor: | Marion Hewicker-Trautwein, Jawad Salman, Michael S. Balzer, Gregor Warnecke, Thierry Siemeni, Jeanette Pichler, Axel Haverich, Danny Jonigk, Klaus Höffler, Katharina Jansson, Reza Poyanmehr, Karolin S. Hacker, Jens Gottlieb, Jörg Frühauf, Martin Werner, Wiebke Sommer, Ann-Kathrin Knöfel, Murat Avsar |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Transplantation Conditioning Swine medicine.medical_treatment Immunology Miniature swine 030230 surgery 03 medical and health sciences 0302 clinical medicine medicine Splenocyte Immune Tolerance Immunology and Allergy Lung transplantation Animals Transplantation Transplantation Chimera Lung business.industry Graft Survival Hematopoietic Stem Cell Transplantation Non myeloablative Perioperative Allografts Peripheral blood Surgery medicine.anatomical_structure Swine Miniature business 030215 immunology Large animal Lung Transplantation |
| Zdroj: | Transplant immunology. 65 |
| ISSN: | 1878-5492 |
| Popis: | We previously induced long-term allograft acceptance in an allogeneic lung transplantation (LTx) model in miniature swine using perioperative non-myeloablative irradiation (IRR) combined with infusion of donor specific alloantigen. In order to improve clinical applicability, we delayed induction with irradiation in this study. Left sided single LTx was performed in minipigs. Group 1 received non-myeloablative irradiation (7Gy thymus and 1.5Gy whole body IRR) before LTx and a perioperative donor specific splenocyte infusion (SpTx). Group 2 received perioperative SpTx but delayed IRR three days after LTx. Group 3 was exposed to delayed IRR without SpTx. Whereas 4 out of 7 animals from the non-delayed group never rejected their grafts and were electively sacrificed on postoperative day (POD) +500, all animals from group 2 rejected their grafts before POD 108. In group 3, 3 out of 8 animals developed long-term allograft acceptance. In all groups, donor leukocyte chimerism peaked up to 20% in peripheral blood one hour after reperfusion of the lung. Group 1 maintained prolonged chimerism beyond POD 7, whereas chimerism levels in groups 2 and 3 decreased continuously thereafter. Delayed irradiation has the potential to improve long-term graft survival, yet not as efficient as a perioperative conditioning protocol. |
| Databáze: | OpenAIRE |
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