Xenotransplantation

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets...

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No abstract text is available yet for this article.

Carbohydrate-antigens widely existed on glycoproteins and glycosphingolipids of all mammalian cells play a crucial role in self-defense and immunity. Xeno-reactive antibodies included in natural human sera play a protecting role in an acute phase-rejection of xenotransplantation. In this study, we investigated the effect of an alteration of glycosylation-pattern, caused by human sialyltransferases such as hST3Gal II or hST6GalNAc IV, on human serum mediated cytotoxicity in pig kidney PK15 cells. From LDH cytotoxicity assay, cytotoxicity to human serum was significantly increased in hST3Gal II and hST6GalNAc IV-transfected PK15 cells, as compared to the control...

Organ transplant is a crucial therapeutic strategy offering a life-saving and transformative medical intervention. It provides an opportunity to improve their quality of life and increase their lifespan. The shortage of organs remains a critical global challenge, leading to a prolonged waiting times for organ receivers, which contributes to an increase in morbidity and mortality rates. Hence, xenotransplantation offered a promising solution to the global shortage of organs through the use of animal organs, leading to an increase in donor availability, reducing waiting times, minimizing organ trafficking, improving genetic engineering advancements, and driving scientific innovation...

BACKGROUND: As sequencing is becoming more broadly available, virus discovery continues. Small DNA viruses contribute to up to 60% of the overall virus load in pigs. Porcine circoviruses (PCVs) are small DNA viruses with a single-stranded circular genome. They are common in pig breeds and have not been properly addressed for their potential risk in xenotransplantation. Whereas PCV1 is non-pathogenic in pigs, PCV2 has been associated with various disease manifestations. Recently two new circoviruses have been described, PCV3 and PCV4...

With decades of pre-clinical studies culminating in the recent clinical application of xenotransplantation, it would appear timely to provide recommendations for operationalizing oversight of xenotransplantation clinical trials. Ethical issues with clinical xenotransplantation have been described for decades, largely centering on animal welfare, the risks posed to the recipient, and public health risks posed by potential spread of xenozoonosis. Much less attention has been given to considerations relating to potentially elevated risks faced by those who may care for or otherwise have close contact with xenograft recipients...

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The 2023 IXA conference, hosted in San Diego, CA, brimmed with excitement against the backdrop of recent innovations in both the pre-clinical and clinical realms with several first-in-human applications of xenotransplantation. The theme, "Pigs are flying," alluded to the adage that xenotransplantation would only become a clinical reality "when pigs fly," suggesting a day that might never come. The event witnessed significant attendance, with 600 participants-the highest in the history of an IXA-IPITA joint congress...

Clinical pig heart transplant experiments have been undertaken, and further clinical experiments and/or clinical trials of gene-edited pig organ xenotransplantation are anticipated. The ethical issues relating to xenotransplantation have been discussed for decades but with little resolution. Consideration of certain ethical issues is more urgent than others, and the need to attain consensus is important. These issues include: (i) patient selection criteria for expanded access and/or clinical trials; (ii) appropriate protection of the patient from xenozoonoses, that is, infections caused by pig microorganisms transferred with the organ graft, (iii) minimization of the risk of a xenozoonosis to bystanders, and (iv) the need for additional public perception studies...

BACKGROUND: In recent years, the implementation of the first case of pig-to-human heart xenotransplantation and the report of three cases of pig-to-brain-dead human recipient kidney transplantation indicate that xenotransplantation is getting closer to clinical application. In the near future, China may also launch clinical trials of kidney xenotransplantation. Therefore, it is necessary to investigate the level of knowledge and acceptance of xenotransplantation among kidney transplant recipients and candidates in China...

BACKGROUND: Xenotransplantation (XTx) is an alternative treatment for organ scarcity. Investigating the acceptance of XTx among patients from diverse cultural and religious backgrounds is essential. This study aimed to evaluate the knowledge, attitudes, and awareness of XTx among patients undergoing liver transplant (LT). METHODS: This descriptive study was conducted between November 2022 and August 2023. The study population comprised LT patients aged ≥18 years who were admitted to the hepatology clinic of a university hospital in Turkey...

We present an updated report highlighting significant developments in the field of xenotransplantation since March 2023. The past six months have witnessed significant strides in the field and the emergence of novel research that is expected to facilitate the journey towards clinical trials. We are reviewing here the most pertinent findings from March 2023 to November 2023.

BACKGROUND: αGal-deficient xenografts are protected from hyperacute rejection during xenotransplantation but are still rejected more rapidly than allografts. Despite studies showing the roles of non-Gal antibodies and αβ T cells in xenograft rejection, the involvement of γδ T cells in xenograft rejection has been limitedly investigated. METHODS: Six male cynomolgus monkeys were transplanted with porcine vessel xenografts from wild-type (n = 3) or GGTA1 knockout (n = 3) pigs...

BACKGROUND: The porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV), is widely distributed in pig populations. It has been shown that PCMV/PRV was transmitted by pig xenotransplants to non-human primates, and significantly reduced the survival time of the recipient. PCMV/PRV was also transmitted during the first transplantation of a pig heart into a human patient. PCMV/PRV establishes a lifelong persistent infection (latency) in the host, is difficult to detect in this stage, and consequential poses a threat to future clinical xenotransplantations...

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Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our lab suggested that the thrombocytopenia may be the result of a species incompatibility in platelet glycosylation. Realization that platelet α-granules contain antibodies caused us to reevaluate whether the thrombocytopenia in liver xenotransplantation could occur because IgM and IgG from inside platelet α-granules bound to pig liver sinusoidal endothelial cells (LSECs)...

BACKGROUND: Pig islet xenotransplantation is a potential treatment for type 1 diabetes. We have shown that maintenance immunosuppression is required to protect genetically modified (GM) porcine islet xenografts from T cell-mediated rejection in baboons. Local expression of a depleting anti-CD2 monoclonal antibody (mAb) by the xenograft may provide an alternative solution. We have previously reported the generation of GGTA1 knock-in transgenic pigs expressing the chimeric anti-CD2 mAb diliximab under an MHC class I promoter (MHCIP)...

Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Genetic manipulations (GM) of pigs offer the possibility of reducing primate humoral and cellular rejection of pig skin xenografts and thus extending graft survival. We compared the survival of skin grafts from pigs with 9-GM with that of autografts and allografts in squirrel monkeys. Monitoring for rejection was by (1) macroscopic examination, (2) histopathological examination of skin biopsies, and (3) measurement of anti-monkey and anti-pig IgM and IgG antibodies...

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