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Transplant Immunology Aug 2023Biological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical... (Review)
Review
INTRODUCTION
Biological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical outcomes of solid organ transplantation, including delayed graft function and frequency of rejection episodes. While much research has focused on the biological age of donor organs, the recipient's biological age may also influence transplantation outcomes. The aim of this scoping review was to identify and provide an overview of the existing evidence regarding biological aging in solid organ transplant recipients and the impact on patient outcomes post-transplant.
METHODS
Literature searches were carried out on PubMed, Web of Science, Google Scholar, Embase and TRIP using the phrases 'solid organ transplant', 'cell senescence', 'cell aging' and 'outcomes', using boolean 'and/or' phrases and MeSH terms. Duplicates were removed and abstracts were reviewed by two independent reviewers. Full papers were then screened for inclusion by two reviewers. Data extraction was carried out using a standardised proforma agreed on prior to starting.
RESULTS
32 studies, including data on a total of 7760 patients, were identified for inclusion in this review; 23 relating to kidney transplant recipients, three to liver transplant, five to lung transplant and one to heart transplantation. A wide range of biomarkers of biological aging have been assessed in kidney transplant recipients, whereas studies of liver, lung and heart transplant have predominantly assessed recipient telomere length. The most robust associations with clinical outcomes are observed in kidney transplant recipients, possibly influenced by the larger number of studies and the use of a wider range of biomarkers of biological aging. In kidney transplant recipients reduced thymic function and accumulation of terminally differentiated T cell populations was associated with reduced risk of acute rejection but increased risk of infection and mortality.
CONCLUSION
Studies to date on biological aging in transplant recipients have been heavily biased to kidney transplant recipients. The results from these studies suggest recipient biological age can influence clinical outcomes and future research is needed to prioritise robust biomarkers of biological aging in transplant recipients.
Topics: Humans; Organ Transplantation; Heart Transplantation; Liver Transplantation; Lung Transplantation; Transplant Recipients; Aging; Graft Rejection
PubMed: 37182719
DOI: 10.1016/j.trim.2023.101851 -
American Journal of Transplantation :... Mar 2024In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the capacity to induce...
In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the capacity to induce senescence in naïve cells. We hypothesized that the engraftment of old organs may induce senescence in younger recipients, promoting age-related pathologies. When performing isogeneic cardiac transplants between age-mismatched C57BL/6 old donor (18 months) mice and young and middle-aged C57BL/6 (3- or 12- month-old) recipients , we observed augmented frequencies of senescent cells in draining lymph nodes, adipose tissue, livers, and hindlimb muscles 30 days after transplantation. These observations went along with compromised physical performance and impaired spatial learning and memory abilities. Systemic levels of the senescence-associated secretory phenotype factors, including mitochondrial DNA (mt-DNA), were elevated in recipients. Of mechanistic relevance, injections of mt-DNA phenocopied effects of age-mismatched organ transplantation on accelerating aging. Single treatment of old donor animals with senolytics prior to transplantation attenuated mt-DNA release and improved physical capacities in young recipients. Collectively, we show that transplanting older organs induces senescence in transplant recipients, resulting in compromised physical and cognitive capacities. Depleting senescent cells with senolytics, in turn, represents a promising approach to improve outcomes of older organs.
Topics: Animals; Mice; Cellular Senescence; Senotherapeutics; Mice, Inbred C57BL; Organ Transplantation; DNA; Aging
PubMed: 37913871
DOI: 10.1016/j.ajt.2023.10.013 -
Frontiers in Public Health 2024
Topics: Humans; Tissue and Organ Procurement; Tissue Donors; Organ Transplantation
PubMed: 38566788
DOI: 10.3389/fpubh.2024.1388317 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
Biosensors Apr 2024Single-cell RNA sequencing is a high-throughput novel method that provides transcriptional profiling of individual cells within biological samples. This method typically... (Review)
Review
Single-cell RNA sequencing is a high-throughput novel method that provides transcriptional profiling of individual cells within biological samples. This method typically uses microfluidics systems to uncover the complex intercellular communication networks and biological pathways buried within highly heterogeneous cell populations in tissues. One important application of this technology sits in the fields of organ and stem cell transplantation, where complications such as graft rejection and other post-transplantation life-threatening issues may occur. In this review, we first focus on research in which single-cell RNA sequencing is used to study the transcriptional profile of transplanted tissues. This technology enables the analysis of the donor and recipient cells and identifies cell types and states associated with transplant complications and pathologies. We also review the use of single-cell RNA sequencing in stem cell implantation. This method enables studying the heterogeneity of normal and pathological stem cells and the heterogeneity in cell populations. With their remarkably rapid pace, the single-cell RNA sequencing methodologies will potentially result in breakthroughs in clinical transplantation in the coming years.
Topics: Animals; Humans; Cell Transplantation; Organ Transplantation; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 38667182
DOI: 10.3390/bios14040189 -
Journal of the Formosan Medical... Oct 2023Solid organ transplant recipients have an increased risk of tuberculosis (TB). Due to the use of immunosuppressants, the incidence of TB among solid organ transplant...
Solid organ transplant recipients have an increased risk of tuberculosis (TB). Due to the use of immunosuppressants, the incidence of TB among solid organ transplant recipients has been consistently reported to be higher than that among the general population. TB frequently develops within the first year after transplantation when a high level of immunosuppression is maintained. Extrapulmonary TB and disseminated TB account for a substantial proportion of TB among solid organ transplant recipients. Treatment of TB among recipients is complicated by the drug-drug interactions between anti-TB drugs and immunosuppressants. TB is associated with an increased risk of graft rejection, graft failure and mortality. Detection and management of latent TB infection among solid organ transplant candidates and recipients have been recommended. However, strategy to mitigate the risk of TB among solid organ transplant recipients has not yet been established in Taiwan. To address the challenges of TB among solid organ transplant recipients, a working group of the Transplantation Society of Taiwan was established. The working group searched literatures on TB among solid organ transplant recipients as well as guidelines and recommendations, and proposed interventions to strengthen TB prevention and care among solid organ transplant recipients.
Topics: Humans; Taiwan; Tuberculosis; Organ Transplantation; Antitubercular Agents; Immunosuppressive Agents
PubMed: 37183074
DOI: 10.1016/j.jfma.2023.04.025 -
Biomaterials Science Mar 2024To date, organ transplantation remains an effective method for treating end-stage diseases of various organs. In recent years, despite the continuous development of... (Review)
Review
To date, organ transplantation remains an effective method for treating end-stage diseases of various organs. In recent years, despite the continuous development of organ transplantation technology, a variety of problems restricting its progress have emerged one after another, and the shortage of donors is at the top of the list. Bioprinting is a very useful tool that has huge application potential in many fields of life science and biotechnology, among which its use in medicine occupies a large area. With the development of bioprinting, advances in medicine have focused on printing cells and tissues for tissue regeneration and reconstruction of viable human organs, such as the heart, kidneys, and bones. In recent years, with the development of organ transplantation, three-dimensional (3D) bioprinting has played an increasingly important role in this field, giving rise to many unsolved problems, including a shortage of organ donors. This review respectively introduces the development of 3D bioprinting as well as its working principles and main applications in the medical field, especially in the applications, and advancements and challenges of 3D bioprinting in organ transplantation. With the continuous update and progress of printing technology and its deeper integration with the medical field, many obstacles will have new solutions, including tissue repair and regeneration, organ reconstruction, ., especially in the field of organ transplantation. 3D printing technology will provide a better solution to the problem of donor shortage.
Topics: Humans; Tissue Engineering; Bioprinting; Regenerative Medicine; Printing, Three-Dimensional; Organ Transplantation
PubMed: 38374788
DOI: 10.1039/d3bm01934a -
BMC Medical Ethics Nov 2023The organ donation and transplantation (ODT) system heavily relies on the willingness of individuals to donate their organs. While it is widely believed that public...
The organ donation and transplantation (ODT) system heavily relies on the willingness of individuals to donate their organs. While it is widely believed that public trust plays a crucial role in shaping donation rates, the empirical support for this assumption remains limited. In order to bridge this knowledge gap, this article takes a foundational approach by elucidating the concept of trust within the context of ODT. By examining the stakeholders involved, identifying influential factors, and mapping the intricate trust relationships among trustors, trustees, and objects of trust, we aim to provide a comprehensive understanding of trust dynamics in ODT. We employ maps and graphs to illustrate the functioning of these trust relationships, enabling a visual representation of the complex interactions within the ODT system. Through this conceptual groundwork, we pave the way for future empirical research to investigate the link between trust and organ donation rates, informed by a clarified understanding of trust in ODT. This study can also provide valuable insights to inform interventions and policies aimed at enhancing organ donation rates.
Topics: Humans; Trust; Surveys and Questionnaires; Tissue and Organ Procurement; Organ Transplantation; Health Knowledge, Attitudes, Practice; Tissue Donors
PubMed: 37914997
DOI: 10.1186/s12910-023-00965-2 -
La Revue Du Praticien Nov 2023EPIDEMIOLOGY OF ORGAN TRANSPLANTATION IN France. The number of transplants has been rising for ten years. Nevertheless, the stabilization of the number of brain-dead...
EPIDEMIOLOGY OF ORGAN TRANSPLANTATION IN France. The number of transplants has been rising for ten years. Nevertheless, the stabilization of the number of brain-dead people identified as potential organ donors, and the persistently high rate of opposition to organ removal, accentuate the substantial gap between the number of candidates for transplantation and the number of transplants performed each year. Strategies are being used to reduce this imbalance, such as broadening the brain-dead donors selection criteria and increasing procurement from living donors and deceased donors after circulatory death. Unfortunately, the Covid-19 pandemic has further aggravated the difference between the supply of transplants and the need.
Topics: Humans; Pandemics; Organ Transplantation; Brain Death; COVID-19; Living Donors
PubMed: 38294440
DOI: No ID Found -
Digestive Diseases and Sciences Sep 2023Transplantation has transformed into a burgeoning field that is rapidly evolving to optimize organ distribution and survival outcomes. The years since 2012 (the last...
IMPORTANCE
Transplantation has transformed into a burgeoning field that is rapidly evolving to optimize organ distribution and survival outcomes. The years since 2012 (the last comprehensive study) have seen changes in transplantation, such as advances in immunotherapy and novel indices, that necessitate an updated analysis of survival benefit.
DESIGN
Our goal was to determine the survival benefit for solid-organ transplants in the United Network for Organ Sharing (UNOS) database for a three decade period and provide updates on advancements since 2012. Our retrospective analysis examined data containing U.S. patient records from September 1, 1987, to September 1, 2021.
RESULTS
We found that 3,430,272 life-years were saved over our transplant period (4.33 life-years saved per patient); kidney-1,998,492 life-years; liver -767,414; heart-435,312; lung-116,625; pancreas-kidney-123,463; pancreas-30,575; intestine-7901. After matching, 3,296,851 life-years were saved. Life-years saved and median survival increased for all organs between 2012 and 2021. Compared to 2012, median survival increased in kidney (from 12.4 to 14.76 years), liver (from 11.6 to 14.59), heart (9.5 to 11.73), lung (5.2 to 5.63), pancreas-kidney (from 14.5 to 16.88), pancreas (from 13.3 to 16.10). When compared to 2012, the percent transplanted increased in kidney, liver, heart, lung, and intestine, while pancreas-kidney and pancreas show decreased percent transplanted.
CONCLUSION
Our study underscores the tremendous survival benefits of solid organ transplantation (over 3.4 million life-years saved) and shows improvements since 2012. Our study also highlights areas of transplantation, notably pancreas transplants, that may necessitate reinvigorated attention.
Topics: Humans; Retrospective Studies; Organ Transplantation; Pancreas Transplantation; Liver; Graft Survival; Registries; Tissue and Organ Procurement
PubMed: 37402977
DOI: 10.1007/s10620-023-08012-1