Xenotransplantation最新文献

Background: Complement inhibitors are important therapeutic drugs after xenotransplantation. However, it is still unclear whether the commonly used clinical complement inhibitors eculizumab and C1 esterase inhibitor (C1-INH) can effectively inhibit complement activation in nonhuman primates.

Methods: The anti-complement activities of eculizumab and C1-INH were evaluated using an in vitro model of normal human serum (NHS) or normal rhesus monkey serum (NRS)-mediated complement-dependent cytotoxicity (CDC), with an immortalized porcine aortic endothelial cell line (iPEC) as the target.

Results: Pretreatment of the NHS with various doses of eculizumab potently inhibited the cell lysis of iPECs. FACS analysis showed that eculizumab potently suppressed the deposition of C5b-9, but not C3c and C4c, on iPECs. However, although eculizumab pretreatment of the NRS had a dose-dependent inhibitory effect on the killing of iPECs, the effect was much weaker than that for similarly treated NHS. Pretreatment of NHS and of NRS with C1-INH produced almost identical dose-dependent inhibitory effects on the killing of iPECs. At the highest concentration (10 IU/mL) of C1-INH used, the CDC was reduced by only about 75%. In addition, C1-INH had moderate inhibitory effects on the deposition of C3c, C4c, and C5b-9 in both humans and rhesus monkeys. When C1-INH was given intravenously to rhesus monkeys at a dose of 17.5 IU/kg, the serum-mediated cell lysis detected in vitro was only slightly reduced, and the maximum inhibition was about 20%.

Conclusion: The inhibitory effect of eculizumab on human complement was significantly stronger than it was on rhesus monkey complement, showing obvious species specificity. The inhibitory effect of C1-INH on complement in humans and rhesus monkeys was similar, but a higher concentration of C1-INH was required in monkeys to achieve a significant inhibitory effect. These results provide a reference basis for the selection of complement inhibitors after clinical or preclinical xenotransplantation.

Background: This study aimed to assess public perceptions, awareness, and attitudes toward xenotransplantation (XTx) and organ donation in Turkey by examining the influence of demographic, socioeconomic, and religious factors to identify barriers and facilitators to organ donation and XTx acceptance METHODS: This cross-sectional survey was conducted with 10 650 participants, selected through stratified sampling to ensure national representation. Data collection was performed via Computer-Assisted Personal Interviewing (CAPI), with structured questionnaires designed to evaluate participants' perspectives on organ donation, XTx, and religious influences, and comparisons were made based on age groups, geographical region, sectarian affiliation, education level, belief categories, and economic status.

Results: Organ donation rates were low across all demographic groups, with notable differences by geographical region, education level, income, age, and religious beliefs. The highest organ donation rate was in Central Anatolia (0.9%), while Southeastern Anatolia had the lowest (0.0%) (p = 0.014). Higher education (p = 0.001) and income levels (p = 0.01) correlated with greater organ donation support. Younger individuals (18-24 years) were less religiously observant, while older participants (65+) displayed the highest religious adherence (p = 0.022). Acceptance of XTx from halal animals was highest in the Aegean region (43.0%) (p = 0.001) and among participants with lower religious adherence (27.4%) (p = 0.004). Approval for XTx from non-halal animals was significantly lower, particularly among highly religious individuals (23.9%). Awareness of XTx-related studies was lowest among participants aged 65+ (9.4%) (p < 0.001) and highest among Maliki participants (27.3%).

Conclusion: This study highlights the influence of demographic, socioeconomic, and religious factors on public attitudes toward organ donation and XTx in Turkey. These findings offer critical insights for policymakers and healthcare professionals to design culturally adaptive strategies that improve organ donation rates and foster XTx acceptance.

This study investigates the impact of COVID-19 vaccination, with a focus on inactivated vaccines, on the production of anti-triple-knockout (TKO) pig antibodies, crucial for xenotransplantation. Although it is known that vaccination influences anti-pig antibody production, the specific effects of COVID-19 vaccines, particularly inactivated forms, remain underexplored. We analyzed serum samples from healthy individuals, patients with end-stage liver disease (ESLD), and liver transplant (LT) recipients to assess antibody binding to TKO pig cells. Our findings reveal a significant difference in anti-TKO pig antibody levels among healthy controls, ESLD patients, and LT recipients. A positive correlation was observed between SARS-CoV-2 IgG and anti-TKO pig IgG levels in ESLD patients. Additionally, LT recipients with active COVID-19 infection showed significantly higher levels of anti-TKO pig IgG antibodies. These results suggest that both inactivated COVID-19 vaccination and infection may potentially increase anti-TKO pig antibody production. This underscores the importance of closely monitoring anti-pig antibody levels in potential xenotransplant recipients following COVID-19 vaccination or infection, highlighting the need for further research to optimize xenotransplantation protocols in the post-pandemic era.

Organ transplantation remains the foremost effective intervention for end-stage organ failure. Nevertheless, the scarcity of donors has resulted in prolonged waiting times for countless patients globally. The advent of xenografts presents a promising solution to the organ shortage crisis. Although the utilization of xenografts has a long history, it is only in recent years that breakthroughs in genetically modified pigs have rendered successful xenotransplantation a feasible option. In the past 4 years, numerous subclinical and clinical trials have involved xenotransplantation from genetically modified pigs to humans. However, the outcomes have been disappointing, necessitating a reassessment of basic and preclinical research to address the emerging challenges. Furthermore, immunosuppressive therapies remain essential in xenotransplantation. The range of immunosuppressive agents, encompassing traditional immunosuppressants and monoclonal antibodies such as anti-CD154/CD40 monoclonal antibodies, exhibits considerable diversity. However, the most effective drug combination for achieving optimal efficacy remains elusive. This review will offer a succinct overview of the results from recent clinical and subclinical xenotransplantation trials. Moreover, it will highlight recent advancements in immunosuppressive strategies and discuss potential future research directions in this field.

Xenotransplantation is finally moving toward clinical application. Despite the progress in survival in preclinical models and the limited attempts at clinical heart transplantation, the initial problem of xenoreactive antibodies in human serum remains a proximal barrier to widespread success in preclinical and clinical settings. Detailed understanding of the pretransplant status of recipients in the preclinical as well as clinical setting is critical to moving the field forward. The differences in the pretransplant donor-specific antibody (DSA) levels in the preclinical and clinical models are outlined so that we can begin to think about the two scenarios in a complementary fashion and facilitate decision making for research priorities and movement into the clinical realm.

Treatments of severe skin injuries have long been a clinical challenge. Early excision of necrotic tissue and skin grafting are essential, yet their effectiveness is hampered by several issues. Autologous and allogeneic skin shortages, the high cost of tissue-engineered skin, and its failure to fully mimic natural skin architecture limit treatment options. Porcine skin is the ideal donor for skin xenotransplantation. It closely resembles human skin in anatomical structure and physiological function, has abundant availability, and involves fewer ethical concerns. Gene-editing technologies allow for the genetic modification of pigs, minimizing xenogeneic immune rejection and zoonotic pathogen transmission risks, thus enhancing the scalability of porcine skin xenotransplantation. This article reviews advantages and limitations of porcine skin as a xenogeneic skin graft, along with the latest preclinical and clinical research on porcine skin xenotransplantation, with a particular emphasis on genetically modified pigs. It aims to highlight the significant potential of gene-edited porcine skin xenotransplantation in treating severe skin wounds. Insights from skin xenotransplantation can also serve as a valuable reference for the development of other organ xenotransplantation. Trial Registration: ClinicalTrials.gov identifier: NCT03695939 and NCT06223269.

Background: Xenotransplantation is a promising field to solve the problem of insufficient allograft and has been actively studied in Korea. However, there are a number of ethical, legal, and social issues to consider, and it is necessary to know the public attitudes regarding them.

Methods: A Computer Aided Web Interview consisting of 22 questionnaire items was conducted to investigate the attitudes of Korean related to xenotransplantation. Participants were selected from Hankook Research MS (Master Sample) panel. A total of 1007 sets of data were finally collected and analyzed with SPSS. A statistical analysis was performed using an independent t-test and chi-square method.

Results: 72.9% of the respondents were positive about xenotransplantation, while 22.2% negative. 61.7% said that they would accept xenotransplantation for incurable diseases. 64.4% agreed with genetically modified pigs for organ resource. 61% agreed that the brain dead could be transplanted first for research purpose, while 32.7% disagreed. The ratio of response that the risk of zoonotic infection is important was 97.2%; the safety issue due to immunosuppression 98.7%; the human identity issue after transplantation 67.4%; and the animal right issue 51.6%. Men were more favorable to xenotransplantation than women on all but one item (stigmatization). There was no significant difference between religions except for the human identity issue.

Conclusion: Korean people are favorable to xenotransplantation as a therapeutic option and also positive with the use of pig even genetically modified in spite of the issue of animal rights. They are also positive with the idea of using the brain dead as study subject for xenotransplantation, which is currently forbidden in Korea.

With gene editing technology and immunosuppressive drugs, kidney xenotransplantation has developed rapidly in recent years. However, as the most cutting-edge medical personnel, there are few reports on the acceptance and awareness of kidney xenotransplantation. This study conducted an online questionnaire survey on medical staff and constructed the first predictive model for the acceptance of kidney xenotransplantation by medical staff through univariate and multivariate analysis of each variable. Their acceptance rate is 72.8%, and it was found that the willingness to donate organs, awareness of kidney xenotransplantation, and residential areas are independent factors affecting their acceptance rate. In addition, the study also found that although healthcare workers have a high acceptance and willingness to share, their awareness of kidney xenotransplantation is relatively low. This reminds us that in order to increase public acceptance of xenotransplantation, the first step is to start with promoting xenotransplantation among medical personnel.

Introduction: Xenotransplantation has emerged as a promising solution to organ shortage, generating numerous publications. However, no studies have analyzed the research dynamics of xenotransplantation research. We aimed to systematically assess xenotransplantation publication activity.

Methods: A systematic literature search was conducted up to November 22, 2024. Studies on xenotransplantation of solid organs and islets of Langerhans from animals to humans, or perfusion with human blood or its derivatives were included. Publication information, publishing journal, publication type, organ, donor species, and topics studied were extracted.

Results: Of 2944 publications, 706 met inclusion criteria: 41.2% original articles, 41.1% reviews, 14.2% publications without original data, 1.6% case reports, 1.3% research letters, 0.6% systematic reviews/meta-analyses. Publication activity displayed two peaks: in the 1990s, driven by the gene editing advancements, and in the early 2020s, following the first pig-to-human transplantation. The top five publishing countries were the USA with (48.2%), Germany (10.2%), UK (5.4%), Sweden (4.8%), and China (4.2%). Xenotransplantation journal accounted for 19.7% of publications, transplantation journals for 27.6%, and general medical journals for 5.4%. Islets of Langerhans were studied in 23.1% of studies, and the most studied organs were heart (21.2%), followed by kidney (17.1%), liver (12.2%), and lung (6.2%). The most represented thematic groups were rejection, immune mechanisms, overall challenges, gene editing, current research, and prospects.

Conclusion: This first systematic assessment of xenotransplantation research highlights its growing global interest and evolving focus areas. The low proportion of publications with original data underscores the need for more original research. Limited representation in general medical journals highlights the importance of engaging a broader audience as clinical trials approach.