The Experts below are selected from a list of 60 Experts worldwide ranked by ideXlab platform
Johann H Karstens - One of the best experts on this subject based on the ideXlab platform.
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irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung but not heart allografts in miniature swine
Transplant International, 2017Co-Authors: W Sommer, Gwen Buechler, K Jansson, M Avsar, A K Knofel, J Salman, Klaus Hoeffler, T Siemeni, Jens Gottlieb, Johann H KarstensAbstract:Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four, and left-sided lung transplantation (LTX) in seven minipigs from gender and SLA mismatched donors. All recipients received non-myeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, three further animals rejected 119, 239 and 360 days post transplantation. In both groups peripheral blood donor Leukocyte chimerism peaked 1h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of Passenger Leukocyte chimerism. This article is protected by copyright. All rights reserved.
David H Sachs - One of the best experts on this subject based on the ideXlab platform.
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recipient matching of Passenger Leukocytes prolongs survival of donor lung allografts in miniature swine
Transplantation, 2015Co-Authors: Maria Lucia Madariaga, Sebastian Michel, Glenn M La Muraglia, Smita Sihag, David A Leonard, Evan A Farkash, Robert B Colvin, Curtis L Cetrulo, Christene A Huang, David H SachsAbstract:Background Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by Passenger Leukocytes in the rejection or acceptance of an organ is unclear. We tested whether recipient-matching of donor graft Passenger Leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation. Methods In the experimental group (group 1), donor lungs were obtained from chimeric swine, in which the Passenger Leukocytes (but not the parenchyma) were major histocompatibility complex-matched to the recipients (n = 3). In the control group (group 2), both the donor parenchyma and the Passenger Leukocytes were major histocompatibility complex-mismatched to the recipients (n = 3). Results Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of Passenger Leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing Passenger Leukocytes matched to the lung recipient (group 1) survived on average 107 days (range, 80-156). Control lung allografts (group 2) survived on average 45 days (range, 29-64; P Conclusions Our data indicate that recipient-matching of Passenger Leukocytes significantly prolongs lung allograft survival.
W Sommer - One of the best experts on this subject based on the ideXlab platform.
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irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung but not heart allografts in miniature swine
Transplant International, 2017Co-Authors: W Sommer, Gwen Buechler, K Jansson, M Avsar, A K Knofel, J Salman, Klaus Hoeffler, T Siemeni, Jens Gottlieb, Johann H KarstensAbstract:Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four, and left-sided lung transplantation (LTX) in seven minipigs from gender and SLA mismatched donors. All recipients received non-myeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, three further animals rejected 119, 239 and 360 days post transplantation. In both groups peripheral blood donor Leukocyte chimerism peaked 1h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of Passenger Leukocyte chimerism. This article is protected by copyright. All rights reserved.
Maria Lucia Madariaga - One of the best experts on this subject based on the ideXlab platform.
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recipient matching of Passenger Leukocytes prolongs survival of donor lung allografts in miniature swine
Transplantation, 2015Co-Authors: Maria Lucia Madariaga, Sebastian Michel, Glenn M La Muraglia, Smita Sihag, David A Leonard, Evan A Farkash, Robert B Colvin, Curtis L Cetrulo, Christene A Huang, David H SachsAbstract:Background Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by Passenger Leukocytes in the rejection or acceptance of an organ is unclear. We tested whether recipient-matching of donor graft Passenger Leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation. Methods In the experimental group (group 1), donor lungs were obtained from chimeric swine, in which the Passenger Leukocytes (but not the parenchyma) were major histocompatibility complex-matched to the recipients (n = 3). In the control group (group 2), both the donor parenchyma and the Passenger Leukocytes were major histocompatibility complex-mismatched to the recipients (n = 3). Results Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of Passenger Leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing Passenger Leukocytes matched to the lung recipient (group 1) survived on average 107 days (range, 80-156). Control lung allografts (group 2) survived on average 45 days (range, 29-64; P Conclusions Our data indicate that recipient-matching of Passenger Leukocytes significantly prolongs lung allograft survival.
Nizar Yonan - One of the best experts on this subject based on the ideXlab platform.
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altered immunogenicity of donor lungs via removal of Passenger Leukocytes using ex vivo lung perfusion
American Journal of Transplantation, 2016Co-Authors: John P Stone, William R Critchley, Triin Major, G Rajan, Ivar Risnes, Helge Scott, Qiuming Liao, Bjorn Wohlfart, Trygve Sjoberg, Nizar YonanAbstract:Passenger Leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor Leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study Passenger Leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor Leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor Leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor Leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.