Xenotransplantation最新文献

{"title":"The case for the therapeutic use of mechanistic/mammalian target of rapamycin (mTOR) inhibitors in xenotransplantation.","authors":"Akihiro Maenaka, Kohei Kinoshita, Hidetaka Hara, David K C Cooper","doi":"10.1111/xen.12802","DOIUrl":"10.1111/xen.12802","url":null,"abstract":"<p><p>The mechanistic/mammalian target of rapamycin (mTOR) is one of the systems that are necessary to maintain cell homeostasis, such as survival, proliferation, and differentiation. mTOR inhibitors (mTOR-Is) are utilized as immunosuppressants and anti-cancer drugs. In organ allotransplantation, current regimens infrequently include an mTOR-I, which are positioned more commonly as alternative immunosuppressants. In clinical allotransplantation, long-term efficacy has been established, but there is a significant incidence of adverse events, for example, inhibition of wound healing, buccal ulceration, anemia, hyperglycemia, dyslipidemia, and thrombocytopenia, some of which are dose-dependent. mTOR-Is have properties that may be especially beneficial in xenotransplantation. These include suppression of T cell proliferation, increases in the number of T regulatory cells, inhibition of pig graft growth, and anti-inflammatory, anti-viral, and anti-cancer effects. We here review the potential benefits and risks of mTOR-Is in xenotransplantation and suggest that the benefits exceed the adverse effects.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 3","pages":"e12802"},"PeriodicalIF":3.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibodies against hyaluronan oligosaccharides in xenotransplantation.","authors":"Daniel Bello-Gil,&nbsp;Sara Olivera-Ardid,&nbsp;Alexander B Tuzikov,&nbsp;Cristina Costa,&nbsp;Nicolai V Bovin,&nbsp;Rafael Mañez","doi":"10.1111/xen.12799","DOIUrl":"https://doi.org/10.1111/xen.12799","url":null,"abstract":"<p><p>Carbohydrate-specific antibodies are significant mediators of xenograft rejection. This study analyzed the carbohydrate specificity of antibodies in baboons before and after xenotransplantation of organs or injection of porcine red blood cells from hDAF transgenic pigs, using a glycan array with structurally defined glycans. Antibodies against hyaluronic acid disaccharide (HA2) showed the highest reactivity at baseline and rose after xenogeneic exposure. We also investigated in the serum of baboons that underwent xenotransplantation with either hDAF or hDAF/hMCP transgenic pig organs and Lewis rats after hamster-skin xenotransplantation the specificity of anti-HA antibodies on a glycan microarray representing HA oligosaccharides containing from two to 40 saccharides. Notably, the HA oligosaccharides ranging from 32 to 40 saccharides exhibited the highest antibody binding intensities at baseline in baboon and rat sera. After xenotransplantation, antibodies against HA38 and HA40 in baboons, and HA32, HA34, and HA36 in rats showed the highest titer increases. The changes of anti-HA IgM and IgG antibodies in rats after skin xenotransplantation was also confirmed by an ELISA specific for HA2, HA24, and HA85 antibodies. Thus, xenotransplantation is associated with increased antibodies against HA-oligosaccharides, which may represent a new target for intervention.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 3","pages":"e12799"},"PeriodicalIF":3.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First transplantation of a pig heart from a multiple gene-modified donor, porcine cytomegalovirus/roseolovirus, and antiviral drugs.","authors":"Joachim Denner","doi":"10.1111/xen.12800","DOIUrl":"https://doi.org/10.1111/xen.12800","url":null,"abstract":"The porcine cytomegalovirus (PCMV) is actually a porcine roseolovirus (PRV).1 As the official International Committee on Taxonomy of Viruses (ITCV) name, suid betaherpesvirus 2 (SuBHV2),2 is not widely used, the abbreviation (PCMV/PRV) will be used to make clear that it is a herpesvirus not closely related to the human cytomegalovirus (HCMV), but to the human herpesviruses 6 and 7 (HHV-6, HHV7), which are also roseoloviruses.3 PCMV/PRV was shown to reduce significantly the survival time of pig xenotransplants in non-human primates. Yamada et al.4 and Sekijima et al.5 reported a reduction of the survival time of pig kidneys from PCMV/PRV-positive donor pigs when transplanted in cynomolgus monkeys and baboons, respectively, in 2014. Already in 2002 Mueller et al.6 reported an activation PCMV in a pig-to-primate model of xenotransplantation in animals with short survival times. In 2016 for the first time an active replication of PCMV following transplantation of a pig heart into a baboon despite undetected virus in the donor pig was reported.7 Denner et al.8 reported a reduction of the survival time of genetically modified pig hearts in baboons. For detailed reviews of these and other studies see Denner.9,10 PCMV/PRVwas also transmitted to the human recipient who received a pig heart in January 2022 in Baltimore, Maryland, USA.11 The clinical features and the steadily increasing virus load observed in the patient in Baltimore are very similar to the features and high virus load observed in baboons, which received a PCMV/PRV-positive heart in Munich.8 Therefore, it is likely that the virus contributed together with other factors to the death of the","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 3","pages":"e12800"},"PeriodicalIF":3.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients' opinions 10 years after receiving encapsulated porcine islet xenotransplantation without immunosuppression.","authors":"Shinichi Matsumoto,&nbsp;Adrian Abalovich,&nbsp;Shaun Wynyard,&nbsp;Mariana E Carulla,&nbsp;David Abalovich","doi":"10.1111/xen.12798","DOIUrl":"https://doi.org/10.1111/xen.12798","url":null,"abstract":"<p><strong>Background: </strong>Previously we performed clinical encapsulated neonatal porcine islet transplantation under comprehensive regulation, and demonstrated the efficacy and safety. To analyze the patients' quality of life (QOL), we assessed patients' opinions 10 years after islet xenotransplantation.</p><p><strong>Methods: </strong>Twenty-one type 1 diabetic patients received microencapsulated neonatal porcine islet transplants in Argentina were enrolled. Seven patients were enrolled in efficacy and safety study and 14 patients were enrolled in safety studies. Patients' opinions related to the current and pre-transplant status of diabetes control, blood glucose levels, severe hypoglycemia, and hyperglycemia required hospitalization were analyzed. In addition, opinions related to islet xenotransplantation were assessed.</p><p><strong>Results: </strong>At the time of this survey, average HbA1c was still significantly lower compared to pre-transplantation (8.5 ± 0.9 (%) at pre-transplant and 7.4 ± 0.5(%) at the survey, p < .05) and average insulin dose were also lower (0.95 ± 0.32 (IU/kg) at pre-transplant and 0.73 ± 0.27 (IU) at the survey). The majority of patients improved diabetes control (71%), blood glucose levels (76%), severe hypoglycemia (86%) and hyperglycemia required hospitalization (76%), and no patients deteriorated in all of the categories when compared with pre-transplantation. No patients had cancer, or psychological problem, and one patient had a serious adverse event. The majority of patients wanted to recommend this treatment to other patients (76%) and receive booster transplantation (85.7%).</p><p><strong>Conclusions: </strong>The majority of patients had positive opinions related to the encapsulated porcine islet xenotransplantation 10 years after transplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 3","pages":"e12798"},"PeriodicalIF":3.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9736631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenotransplantation literature update March 2021-March 2023.","authors":"Shani Kamberi,&nbsp;Raphael P H Meier","doi":"10.1111/xen.12805","DOIUrl":"https://doi.org/10.1111/xen.12805","url":null,"abstract":"<p><p>After a significant hiatus imposed by the COVID-19 pandemic, we hereby restart Xenotransplantation literature updates. With the recently performed clinical xenotransplantation cases and the much-heightened interest in the field, we have determined that this is an optimal time to reinstate this section. There has been an invigorated focus on unique challenges posed by pig-to-human xenotransplantation, and specific attention will be given to this aspect. In this issue, we aimed to cover the gap and compiled the most relevant publications from March 2021 to March 2023.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 3","pages":"e12805"},"PeriodicalIF":3.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9737757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1111/xen.12755","DOIUrl":"https://doi.org/10.1111/xen.12755","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42041849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenotransplantation: A historical-ethical account of viewpoints.","authors":"Daniel Rodger, Daniel J Hurst, David Kc Cooper","doi":"10.1111/xen.12797","DOIUrl":"10.1111/xen.12797","url":null,"abstract":"<p><p>Formal clinical trials of pig-to-human organ transplant-known asxenotransplantation-may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical-ethical account of xenotransplantation and details if or how viewpoints have shifted over time.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 2","pages":"e12797"},"PeriodicalIF":3.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9442133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attitudes of patients with renal disease on xenotransplantation: A systematic review.","authors":"Isabel DeLaura, Imran J Anwar, Joseph Ladowski, Alejandra Patino, Sarah Cantrell, Scott Sanoff","doi":"10.1111/xen.12794","DOIUrl":"10.1111/xen.12794","url":null,"abstract":"<p><strong>Background: </strong>Recent years have seen major advancements in xenotransplantation: the first pig-to-human heart transplant, the development of a brain-dead recipient model for kidney xenotransplantation, and the registration of the first xenokidney clinical trial. The attitudes of patients with kidney disease or transplants on xenotransplantation and an assessment of their reservations and considerations regarding the technology are crucial to successful clinical translation and eventual widespread implementation.</p><p><strong>Methods: </strong>This systematic review was registered through PROSPERO (CRD42022344581) prior to initiation of the study and reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. We included studies that evaluated attitudes towards and willingness to undergo xenotransplantation in patients with end-stage renal disease (ESRD), including those who had already undergone transplantation. MEDLINE (via Ovid), Embase (via Elsevier), and Web of Science (via Clarivate) were searched from database inception to July 15, 2022 by an experienced medical librarian for studies on xenotransplantation and attitudes. Abstracts and full text were screened using Covidence software and data items regarding study methodology, patient demographics, and attitudes regarding xenotransplantation were extracted using Microsoft Excel. Risk of bias assessments were performed using the Critical Appraisal Skills Programmed and National Institute of Health study quality assessment tools.</p><p><strong>Results: </strong>Of 1992 studies identified, 14 studies met the inclusion criteria. These studies were conducted across eight countries, four in the United States, for a total of 3114 patients on the kidney waitlist or with a kidney transplant. All patients were over 17 years old and 58% were male. Acceptance of a xenotransplant was assessed using surveys in 12 studies. Sixty-three percent (n = 1354) of kidney patients reported that they would accept a xenotransplant with function comparable to that of an allotransplant. Acceptance of xenografts with inferior function to allografts (15%) or as bridge organs (35%) to allotransplantation was lower. Specific concerns expressed by patients included graft function, infection, social stigma, and animal rights. Subgroup analyses showed higher acceptance in already transplanted compared to waitlist patients and white compared to Black Americans.</p><p><strong>Conclusion: </strong>An understanding of patient attitudes and reservations is key to the successful execution of the first xenotransplantation clinical trials. This study compiles important factors to consider, such as patient concerns, attitudes regarding practical clinical scenarios for the use of xenotransplantation, and the impact of demographic factors on acceptance of this emerging technology.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 2","pages":"e12794"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-gap peripheral nerve repair using xenogeneic transplants in rhesus macaques.","authors":"Paul Holzer,&nbsp;Elizabeth J Chang,&nbsp;Kaitlyn Rogers,&nbsp;Jamie Tarlton,&nbsp;Diana Lu,&nbsp;Natasha Gillespie,&nbsp;Jon Adkins,&nbsp;Monica Metea,&nbsp;Alan LaRochelle,&nbsp;Joan Wicks,&nbsp;Buket Onel,&nbsp;Steve Gullans,&nbsp;Joshua C Doloff,&nbsp;Linda Scobie,&nbsp;Curtis L Cetrulo,&nbsp;Rod Monroy","doi":"10.1111/xen.12792","DOIUrl":"https://doi.org/10.1111/xen.12792","url":null,"abstract":"<p><p>Surgical intervention is required to successfully treat severe, large-gap (≥4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human and porcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT-KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, and importantly, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials similar to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our preliminary findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross-species cells, and highlight the broader clinical potential of xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 2","pages":"e12792"},"PeriodicalIF":3.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9495066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1111/xen.12752","DOIUrl":"https://doi.org/10.1111/xen.12752","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44957506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}