Considerable shortages in the supply of available organs continue to plague the field of solid organ transplantation. Despite changes in allocation, as well as the utilization of extended criteria and living donors, the number of patients waiting for organs continues to grow at an alarming pace. Xenotransplantation, cross-species solid organ transplantation, offers one potential solution to this dilemma. Previous extensive research dedicated to this field has allowed for resolution of xenograft failure due to acute rejection, leaving new areas of unresolved challenges as barriers to success in large animal models. Specific to kidney xenotransplantation, recent data seems to indicate that graft compromise can occur due to discrepancies in growth between breeds of donors and significant proteinuria leading to nephrotic syndrome in the recipient. Given these potential limitations, herein, we review potential pathways behind proteinuria, as well as potential causative factors related to growth discrepancies. Control of both of these has the potential to allow xenotransplantation to become clinically applicable in an effort to resolve this organ shortage crisis.
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http://dx.doi.org/10.1155/2018/6413012 | DOI Listing |
Transpl Int
December 2024
Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
Xenotransplantation of porcine organs has made remarkable progress towards clinical application. A key factor has been the generation of genetically multi-modified source pigs for xenotransplants, protected against immune rejection and coagulation dysregulation. While efficient gene editing tools and multi-cistronic expression cassettes facilitate sophisticated and complex genetic modifications with multiple gene knockouts and protective transgenes, an increasing number of independently segregating genetic units complicates the breeding of the source pigs.
View Article and Find Full Text PDFTranspl Int
December 2024
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Based on promising results obtained in primate models, pioneers in the US have now started to explore the new frontier of genetically-edited pig-to-human transplantation. The recent transition of xenotransplantation into clinical medicine has included transplants in brain-dead subjects and the compassionate use of xenotransplants in living recipients without options for allotransplantation. While the barrier of hyperacute rejection seems to be successfully overcome by gene editing of donor pigs, the occurrence of accelerated rejection could pose significant limitations to the success of the procedure.
View Article and Find Full Text PDFFront Transplant
November 2024
Columbia Center of Translational Immunology, Columbia University, New York, NY, United States.
Background: Despite advances in immunosuppressive therapies, chronic rejection and immunosuppression-related complications remain significant challenges in transplantation. Developing transplantation tolerance through thymus transplantation may offer a solution. This paper details our technique for procuring and transplanting porcine vascularized thymic lobes (VTL), which can be utilized to study and research allogeneic and xenogeneic transplantation models in large animals.
View Article and Find Full Text PDFFront Transplant
November 2024
Columbia Center for Transplantation Immunology, Columbia University, New York, NY, United States.
Introduction: Thymokidneys (TK) have been constructed to transplant life-supporting kidney grafts containing donor thymic tissue to induce transplant tolerance. Historically, TKs were constructed by inserting pieces of thymus tissue under the kidney capsule using an intra-abdominal or posterior retroperitoneal (lateral/flank) approach. The intra-abdominal approach is technically easier but causes intra-abdominal adhesions and makes kidney procurement more challenging.
View Article and Find Full Text PDFTher Drug Monit
November 2024
Department of Nephrology and Transplantation, Erasmus Medical Center, University Medical Center, Rotterdam, the Netherlands; and.
Purpose: In this review, the authors summarized the latest developments in costimulatory blockade to prevent rejection after solid organ transplantation (SOT) and discussed possibilities for future research and the need for therapeutic drug monitoring (TDM) of these agents.
Methods: Studies about costimulatory blockers in SOT in humans or animal transplant models in the past decade (2014-2024) were systematically reviewed in PubMed, European Union clinical trials (EudraCT), and ClinicalTrials.gov.
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