Xenotransplantation最新文献

Background: Xenotransplantation (XTx), as a crucial direction for addressing the shortage of allogeneic donors, has achieved significant progress and garnered widespread attention in China. However, this field still faces multiple challenges at the ethical, legal, and social levels, making it particularly critical to systematically understand public attitudes and perceptions regarding XTx. This study aims to investigate the knowledge and acceptance of the Chinese population toward XTx.

Methods: A 47-item questionnaire was designed to explore the Chinese public's knowledge and acceptance of XTx. It was distributed and collected via the "Wenjuanxing" platform (a Chinese online survey tool), getting 2651 valid responses. Nonparametric tests and generalized linear models were performed with SPSS software to test the proposed relationships.

Results: The overall public acceptance score for XTx was 98 (82, 104), indicating a moderate level of acceptance (67.59%). Among the dimensions, "Knowledge and Attitude" scored the highest (72.72%), while "Risks and Concerns" was the lowest (60.00%). Multivariable analyses identified key independent factors influencing acceptance. Males, individuals with higher education, urban residents, and those willing about uncompensated donation had significantly higher total scores. Conversely, females, individuals with religious beliefs, nonmedical professionals, and those with personal/family-related transplant experiences had significantly lower scores. Dimension-specific analyses yielded several insights. Higher income mitigated risk concerns. Additionally, healthcare professionals held more positive views on efficacy and cost than other groups.

Conclusions: The Chinese public demonstrates a relatively high level of awareness and a moderately favorable acceptance of XTx. However, respondents exhibit incomplete knowledge of inherent residual risks, immune rejection, and long-term efficacy in XTx. At the same time, they hold overly optimistic expectations regarding its therapeutic outcomes and associated costs.

The shortage of transplantable livers and high waitlist mortality rates have accelerated the clinical translation of liver xenotransplantation. Recent milestones, including extracorporeal perfusion models and gene-edited pig-to-human transplants in both decedents and living patients, indicate that clinical trials may be imminent. While the ethics of solid organ xenotransplantation generally-such as animal welfare, xenozoonosis, and informed consent-have been debated, the specific implications of liver xenotransplantation remain underexplored. This article examines these unique challenges. We argue that pediatric liver xenotransplantation research might proceed simultaneously with adult research due to high waitlist mortality among infants. In adults, we analyze how liver xenotransplantation intersects with historical controversies regarding patient selection, specifically concerning alcohol-associated liver disease and hepatocellular carcinoma. We explore the ethical risks of a potential dual pathway allocation system that could bifurcate waitlists based on disease etiology, raising concerns regarding distributive justice and the stigmatization of addiction. Finally, we consider whether xenografts might serve as a trial of time for patients currently ineligible for allotransplantation.

Xenotransplantation has emerged as a potential solution to the critical shortage of donor organs, with recent breakthroughs demonstrating transplantation of genetically modified porcine organs into humans. In Japan, the Ministry of Health, Labour and Welfare has advanced the regulatory review framework to accelerate research and enable the nation's first clinical xenotransplantation. Unlike conventional pharmaceutical pathways, the Act on the Safety of Regenerative Medicine provides a distinctive framework that allows xenotransplantation to be delivered as a medical procedure rather than as a medicinal product. Under this law, a multi-step review process and adherence to specific guidelines, this framework may facilitate early-phase clinical research while safeguarding public health, offering an alternative model to regulatory systems in the other countries.

The global shortage of organs for allotransplantation contributes to illicit trade in human organs. While clinical xenotransplantation is proposed as a potential solution to this global shortage, diverse factors contribute to human organ trafficking including global shortages, underdeveloped and under supported organ procurement infrastructures and related legislation, inadequate access to advanced medical therapies or insurance coverage, and poverty and corruption allowing exploitation of vulnerable populations. This article assesses competing predictions regarding the relationship between the advent of xenotransplantation and the global black market for organs. Some argue that a plentiful supply of xenografts will reduce or eliminate the demand that drives organ trafficking. This analysis highlights significant countervailing risks regarding (i) cost, availability, and equitable access; (ii) perceived quality / desirability of an allograft versus a xenograft; and (iii) the emergence of new illicit markets. We conclude that the effect of xenotransplantation on organ trafficking is presently unpredictable but an important metric for success in this field.

Background: Severe thrombocytopenia and coagulation dysregulation remain major barriers to survival in pig-to-primate liver xenotransplantation models.

Methods: Porcine livers with five genetic modifications (GTKO, CMAHKO, β4GalNT2KO, hCD55, and hTBM) were orthotopically transplanted into four Tibetan macaques under two conventional immunosuppressive protocols. Longitudinal monitoring included graft and multi-organ function, hematology, coagulation, and immune responses. Histopathological and immunohistochemical analyses were performed to characterize graft and recipient pathology.

Results: High expression of human thrombomodulin (hTBM) in donor livers effectively prevented early rapid and severe thrombocytopenia, with three of four recipients maintaining platelets >100 × 10⁹/L. Thrombotic microangiopathy (TMA) was absent in grafts and recipient organs despite transient hypercoagulability. No spontaneous bleeding occurred in three of four cases. However, porcine livers failed to synthesize functional coagulation factor II, protein C, and protein S, contributing to progressive coagulopathy. While early graft function and coagulation remained stable for four posttransplant days, late dysfunction ensued, characterized by impaired coagulation factor synthesis and progressive graft failure. Antibody-mediated rejection, accompanied by IgM/IgG/C4b deposition, anti-TKO antibody increase, and pvWF upregulation, triggered injury that was amplified by innate and T cell-mediated responses.

Conclusions: GTKO/CMAHKO/β4GalNT2KO/hCD55/hTBM donor liver transplantation was associated with an absence of early severe thrombocytopenia, transfusion requirement, and TMA, but long-term survival was limited by immune-mediated rejection and cross-species incompatibilities in coagulation factor synthesis. Optimizing (i) donor genetic modifications and (ii) immunosuppressive therapy, with (iii) replacement of targeted coagulation factors will be crucial for achieving durable survival in pig liver xenotransplantation.

Xenotransplantation has garnered significant attention in recent years, characterized by substantial progress and rapid developments within the field. The objective of this study was to investigate the evolving trends and emerging research hotspots in xenotransplantation through a comprehensive bibliometric analysis. We conducted an analysis of literature published between 1980 and 2025, sourced from the Web of Science Core Collection. Data processing, analysis, and visualization were performed using VOSviewer, CiteSpace, the Bibliometric R package, and Scimage Graphica. A total of 7880 articles spanning 45 years were included in the analysis. The United States emerged as the predominant contributor to the field, both in terms of article output and institutional involvement. Professor David K. C. Cooper was identified as the leading author, with the highest number of publications on xenotransplantation. The journal Xenotransplantation was found to be the most prolific in terms of article publication. Key research hotspots identified through this analysis include the selection of gene-editing strategies for pigs, the use of genetically modified pigs as donors for various cells, tissues, and organs, as well as the focus on clinical trials and translational studies aimed at advancing xenotransplantation.

Background: Xenotransplantation, using gene-edited pigs, represents an important approach to overcoming human organ shortages. A major obstacle to xenotransplantation is antibody-mediated rejection (AMR), which leads to xenograft injury by activating complement and effector cells through the fragment crystallizable domain (Fc) of donor-specific antibodies (DSAs). Therefore, we designed a strategy to express the human high-affinity IgG receptor (hCD64) on porcine endothelial cells to competitively bind IgG and protect xenografts from AMR.

Methods: The lentiviral transduction of hCD64 into porcine aortic endothelial cells (PAEC) from wild-type and GTKO pigs was validated using quantitative reverse transcription (qRT)-PCR, Western blot, and flow cytometry. The effects of hCD64 transduction and activation on cell physiology were assessed using RNA sequencing. The IgG Fc-binding capacity of hCD64 was validated using flow cytometry and ELISA. Finally, the protective effect of hCD64 against complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in PAECs and GTKO PAECs was confirmed through apoptosis assays.

Results: hCD64 was stably expressed at both mRNA and protein levels in PAEC^hCD64 and PAEC^GTKO/hCD64, with both exhibiting normal physiological functions. PAEC^hCD64 and PAEC^GTKO/hCD64 bound free human IgG in a concentration-dependent manner. In contrast, hCD64 did not bind to human IgM or pig and mouse IgG. In the CDC assay, the survival of PAEC^hCD64 was significantly higher than that of PAEC^NC (67.89% vs. 46.03%); moreover, the survival in GTKO PAEC had the same trend (85.18% vs. 71.09%). Similar results were obtained in the assay of ADCC: the survival rates of PAEC^hCD64 and PAEC^NC were 67.27% and 44.95%, respectively, and the survival of PAEC^GTKO/hCD64 and PAEC^GTKO/NC were 80.73% and 66.62%, respectively. Pre-saturation with high doses of human-derived mAbs did not abrogate the protective function of hCD64.

Conclusion: hCD64 expression may partially protect xenografts from AMR through its ability to bind competitively with DSAs IgG Fc.

Whole blood and its constituents are primary treatments for numerous human patients with a vast array of clinical conditions. Each year, these include >10 million blood transfusions performed in the USA and approximately 16 million patients globally that receive plasma-derived medicinal products costing $30 billion. As the clinical indications and demand for blood products continue to grow, there is a critical impetus for establishing sources that are more reliable, cost-effective, and efficacious than the current system that is largely built around samples derived from human donors. In particular, genetically-engineered pigs that have been developed for solid organ xenotransplantation could also serve as a source of blood products, representing a potential source for fulfilling global clinical needs. Here we provide an overview of the blood product economy and assess the feasibility of genetically-engineered pigs as a source of clinical-grade blood products for use in human recipients. Although the potential need for these products is immense, we draw attention to the special requirement for them in patients with pig organ grafts.