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Nature Reviews. Nephrology Dec 2022A major limitation of organ allotransplantation is the insufficient supply of donor organs. Consequently, thousands of patients die every year while waiting for a... (Review)
Review
A major limitation of organ allotransplantation is the insufficient supply of donor organs. Consequently, thousands of patients die every year while waiting for a transplant. Progress in xenotransplantation that has permitted pig organ graft survivals of years in non-human primates has led to renewed excitement about the potential of this approach to alleviate the organ shortage. In 2022, the first pig-to-human heart transplant was performed on a compassionate use basis, and xenotransplantation experiments using pig kidneys in deceased human recipients provided encouraging data. Many advances in xenotransplantation have resulted from improvements in the ability to genetically modify pigs using CRISPR-Cas9 and other methodologies. Gene editing has the capacity to generate pig organs that more closely resemble those of humans and are hence more physiologically compatible and less prone to rejection. Despite such modifications, immune responses to xenografts remain powerful and multi-faceted, involving innate immune components that do not attack allografts. Thus, the induction of innate and adaptive immune tolerance to prevent rejection while preserving the capacity of the immune system to protect the recipient and the graft from infection is desirable to enable clinical xenotransplantation.
Topics: Humans; Animals; Swine; Transplantation, Heterologous; Graft Survival; Primates; Tissue and Organ Procurement; Transplants; Graft Rejection
PubMed: 36198911
DOI: 10.1038/s41581-022-00624-6 -
Frontiers in Immunology 2022Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over... (Review)
Review
Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft. Given the morbidity, mortality, costs, or absence of supportive treatments, xenotransplant has the potential to address the critical shortage in organ grafts. Last decade research efforts focused on creation of donor organs from pigs with various genes edited out using CRISPR technologies and utilizing non-human primates for trial. Three groups in the United States have recently moved forward with trials in human subjects and obtained initial successful results with pig-to-human heart and kidney xenotransplantation. This review serves as a brief discussion of the recent progress in xenotransplantation research, particularly as it concerns utilization of porcine heart, renal, and liver xenografts in clinical practice.
Topics: Animals; Heterografts; Humans; Primates; Swine; Tissue Donors; Transplantation, Heterologous; Transplants; United States
PubMed: 35757701
DOI: 10.3389/fimmu.2022.900594 -
Transplant International : Official... Nov 2021The future clinical application of animal-to-human transplantation (xenotransplantation) is of importance to society as a whole. Favourable preclinical data relevant to... (Review)
Review
The future clinical application of animal-to-human transplantation (xenotransplantation) is of importance to society as a whole. Favourable preclinical data relevant to cell, tissue and solid organ xenotransplants have been obtained from many animal models utilizing genetic engineering and protocols of pathogen-free husbandry. Findings have reached a tipping point, and xenotransplantation of solid organs is approaching clinical evaluation, the process of which now requires close deliberation. Such discussions include considering when there is sufficient evidence from preclinical animal studies to start first-in-human xenotransplantation trials. The present article is based on evidence and opinions formulated by members of the European Society for Organ Transplantation who are involved in the Transplantation Learning Journey project. The article includes a brief overview of preclinical concepts and biology of solid organ xenotransplantation, discusses the selection of candidates for first-in-human studies and considers requirements for study design and conduct. In addition, the paper emphasizes the need for a regulatory framework for xenotransplantation of solid organs and the essential requirement for input from public and patient stakeholders.
Topics: Animals; Heterografts; Humans; Models, Animal; Organ Transplantation; Transplantation, Heterologous; Transplants
PubMed: 34459040
DOI: 10.1111/tri.14031 -
American Journal of Transplantation :... Sep 2021The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of... (Review)
Review
The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another. In this review, we summarize the current data available for management and care of the failing allograft. Additionally, we discuss a suggested plan for immunosuppression weaning based upon the availability of re-transplantation and residual allograft function. We propose a shared-care model in which there is improved coordination between transplant providers and general nephrologists so that immunosuppression management and preparation for renal replacement therapy and/or repeat transplantation can be conducted with the goal of improved outcomes and decreased morbidity in this vulnerable patient group.
Topics: Allografts; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Renal Dialysis; Transplantation, Homologous
PubMed: 34115439
DOI: 10.1111/ajt.16717 -
American Journal of Transplantation :... Aug 2021Current short-term kidney post-transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national...
Current short-term kidney post-transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000-2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014-2017 (1995-1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995-1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995-1999 to an estimated 19.2 years for transplants in 2014-2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.
Topics: Adult; Female; Graft Rejection; Graft Survival; Humans; Kidney; Kidney Transplantation; Living Donors; Male; Middle Aged; Registries; Transplants
PubMed: 33346917
DOI: 10.1111/ajt.16463 -
American Journal of Transplantation :... Apr 2022
Topics: Heterografts; Transplantation, Heterologous
PubMed: 35073605
DOI: 10.1111/ajt.16963 -
Current Opinion in Organ Transplantation Aug 2020Transplant pathology contributes substantially to personalized treatment of organ allograft recipients. Rapidly advancing next-generation human leukocyte antigen (HLA)... (Review)
Review
PURPOSE OF REVIEW
Transplant pathology contributes substantially to personalized treatment of organ allograft recipients. Rapidly advancing next-generation human leukocyte antigen (HLA) sequencing and pathology are enhancing the abilities to improve donor/recipient matching and allograft monitoring.
RECENT FINDINGS
The present review summarizes the workflow of a prototypical patient through a pathology practice, highlighting histocompatibility assessment and pathologic review of tissues as areas that are evolving to incorporate next-generation technologies while emphasizing critical needs of the field.
SUMMARY
Successful organ transplantation starts with the most precise pratical donor-recipient histocompatibility matching. Next-generation sequencing provides the highest resolution donor-recipient matching and enables eplet mismatch scores and more precise monitoring of donor-specific antibodies (DSAs) that may arise after transplant. Multiplex labeling combined with hand-crafted machine learning is transforming traditional histopathology. The combination of traditional blood/body fluid laboratory tests, eplet and DSA analysis, traditional and next-generation histopathology, and -omics-based platforms enables risk stratification and identification of early subclinical molecular-based changes that precede a decline in allograft function. Needs include software integration of data derived from diverse platforms that can render the most accurate assessment of allograft health and needs for immunosuppression adjustments.
Topics: HLA Antigens; Histocompatibility Testing; Humans; Organ Transplantation; Precision Medicine; Tissue Donors; Transplantation Immunology; Transplantation, Homologous; Transplants
PubMed: 32520786
DOI: 10.1097/MOT.0000000000000772 -
Transplant International : Official... 2024
Topics: Humans; Liver Transplantation; Transplants; Perfusion; Organ Preservation; Graft Survival; Liver
PubMed: 38544563
DOI: 10.3389/ti.2024.12853 -
Medicina (Kaunas, Lithuania) May 2021Since its first detection in 1948, donor-derived cell-free DNA (dd-cfDNA) has been employed for a myriad of indications in various medical specialties. It has had a... (Review)
Review
Since its first detection in 1948, donor-derived cell-free DNA (dd-cfDNA) has been employed for a myriad of indications in various medical specialties. It has had a far-reaching impact in solid organ transplantation, with the most widespread utilization in kidney transplantation for the surveillance and detection of allograft rejection. The purpose of this review is to track the arc of this revolutionary test-from origins to current use-along with examining challenges and future prospects though the lens of transplant nephrology.
Topics: Cell-Free Nucleic Acids; Graft Rejection; Humans; Kidney Transplantation; Tissue Donors; Transplants
PubMed: 34065914
DOI: 10.3390/medicina57050482 -
Experimental and Clinical... Dec 2018The evolution and success of intestinal and multi-visceral transplantation over the past 20 years have raised the issue of difficult or even impossible abdominal... (Review)
Review
The evolution and success of intestinal and multi-visceral transplantation over the past 20 years have raised the issue of difficult or even impossible abdominal closure, a topic rarely encountered in other fields of transplantation. Different techniques have been proposed to address this topic. The choice depends on the transplant team's expertise and/or the availability of a plastic surgery service. Abdominal wall transplant is a type of composite tissue allograft that can be utilized to reconstitute the abdominal domains of patients who undergo intestinal transplant, and the results are encouraging. It is an effective option to achieve primary abdominal closure after intestinal transplant. In its full-thickness form, it may be useful for monitoring rejection or viability of visceral organs. Our aim is to review the role of abdominal wall transplant in achieving tension-free closure of the abdomen.
Topics: Abdominal Wall; Composite Tissue Allografts; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Intestines; Organ Transplantation; Risk Factors; Time Factors; Treatment Outcome; Vascularized Composite Allotransplantation; Wound Closure Techniques
PubMed: 30373506
DOI: 10.6002/ect.2018.0189