XenotransplantationPub Date : 2024-03-01Epub Date: 2023-08-02DOI: 10.1111/xen.12818
Songzhe He, Tao Li, Hao Feng, Jiaxiang Du, David K C Cooper, Hidetaka Hara, Hongtao Jiang, Dengke Pan, Gang Chen, Yi Wang
{"title":"Incidence of serum antibodies to xenoantigens on triple-knockout pig cells in different human groups.","authors":"Songzhe He, Tao Li, Hao Feng, Jiaxiang Du, David K C Cooper, Hidetaka Hara, Hongtao Jiang, Dengke Pan, Gang Chen, Yi Wang","doi":"10.1111/xen.12818","DOIUrl":"10.1111/xen.12818","url":null,"abstract":"<p><strong>Background: </strong>Xenoantigens other than Gal, Neu5Gc, and Sda may be playing a role in pig graft rejection. We investigated the incidence of antibodies to unknown pig xenoantigen in different human groups.</p><p><strong>Methods: </strong>We collected blood from TKO/hCD55 pigs (n = 3), and isolated PBMCs and RBCs. Serum samples were collected from (i) healthy human volunteers (n = 43), (ii) patients with end-stage renal disease (ESRD) (n = 87), (iii) the same patients after kidney allotransplantation (n = 50), and (iv) renal allotransplant recipients experiencing T cell-mediated rejection (allo-TCMR, n = 10). The sera were initially incubated with TKO/hCD55 pRBCs (1 × 10<sup>8</sup> cells) for 1 h to absorb anti-pig antibodies (except against SLA and possibly other antigens not expressed on pRBCs) and then the serum (absorbed or unabsorbed) was tested for antibody binding and complement-dependent cytotoxicity (CDC) to TKO/hCD55 pig PBMCs.</p><p><strong>Results: </strong>A significant reduction in IgM/IgG binding and CDC was observed in the absorbed sera. Serum obtained before and after renal allotransplantation showed no significant difference in IgM or IgG binding to, or in CDC of, TKO/hCD55 pig cells. IgM antibodies (but rarely IgG) against unknown xenoantigens expressed on TKO/hCD55 PBMCs, possibly against swine leukocyte antigens, were documented in healthy humans, patients with ESRD, and those with renal allografts undergoing acute T cell rejection. IgM (but not CDC) was higher in patients experiencing allo-TCMR.</p><p><strong>Conclusion: </strong>Human sera contain IgM antibodies against unknown pig xenoantigens expressed on TKO/hCD55 pPBMCs. Although not confirmed in the present study, the targets for these antibodies may include swine leukocyte antigens.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":"e12818"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922992","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}
Maya Ghazi, Aalaa Saleh, Malak Abdallah, Diala El Masri, Jad El Masri, Lemir Majed El Ayoubi, Jihad Hawi, Abdo Jurjus
{"title":"Barriers toward xenotransplantation in Arab World.","authors":"Maya Ghazi, Aalaa Saleh, Malak Abdallah, Diala El Masri, Jad El Masri, Lemir Majed El Ayoubi, Jihad Hawi, Abdo Jurjus","doi":"10.1111/xen.12852","DOIUrl":"10.1111/xen.12852","url":null,"abstract":"<p><p>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. Even though xenotransplantation has many benefits in the clinical setting, it has many barriers that are hindering its achievements and constraining its occurrence. Some barriers to xenotransplant are general, such as the immunological barrier, while others are specific to certain regions due to local causes. The Arab region exhibits disparities in clinical settings compared to the global context, marked by the huge economic crisis and a shortage of trained healthcare professionals. Considering the huge resources and advancements needed in the field of xenotransplantation, this review aims to explore the specific barriers toward xenotransplantation in the Arab countries, highlighting the challenges to overcome these barriers.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 2","pages":"e12852"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207662","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":"A murine groin site cardiac transplantation model-applicable tool for studying roles of peripheral lymph nodes in transplantation.","authors":"Yaguang Li, Wenjia Yuan, Mingda Zhong, Julia Qi, Xinguo Zheng, Xubiao Xie, Tengfang Li, Hedong Zhang, Xin Jiang, Longkai Peng, Helong Dai","doi":"10.1111/xen.12817","DOIUrl":"10.1111/xen.12817","url":null,"abstract":"<p><p>The murine heterotopic cardiac transplantation model has been widely used to study antigen-specific immune responses or new immunosuppressive agents, which have a strong correlation with peripheral lymph nodes. Thus, a new organ transplantation model that is applicable to related studies is needed. Here, we describe a groin-site murine heart transplantation model using a cuff technique, in which the donor aorta and pulmonary artery are anastomosed to the truncated femoral vessels of the recipient. The mean survival time (MST) of the grafts in BALB/c-to-C57BL/6 allo-transplant group was 7.2 ± 0.3 days, and 1.9 ± 0.2 days in BALB/c-to-Sprague-Dawley (SD) rat xeno-transplant group. H&E results show that donor hearts from both groups demonstrate typical pathological features at the endpoint. Evans Blue tracing revealed that the popliteal lymph nodes of the grafted side hindlimb are larger than those of the contralateral side. Moreover, IHC staining for CD3, CD20 shows that the germinal center and cortex region of the grafted side of popliteal lymph nodes is apparently increased than that of the contralateral side. To sum up, this model may serve as an ideal model to study the role of peripheral lymph nodes in organ transplant rejection. In addition, extra-peritoneal grafting makes a step forward in animal welfare under the 3Rs' principle (Replacement, Reduction, Refinement).</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":"e12817"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319342","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}
Jong-Min Kim, Seong-Jun Kang, So-Hee Hong, Hyunwoo Chung, Jun-Seop Shin, Byoung-Hoon Min, Hyun Je Kim, Jongwon Ha, Chung-Gyu Park
{"title":"Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.","authors":"Jong-Min Kim, Seong-Jun Kang, So-Hee Hong, Hyunwoo Chung, Jun-Seop Shin, Byoung-Hoon Min, Hyun Je Kim, Jongwon Ha, Chung-Gyu Park","doi":"10.1111/xen.12850","DOIUrl":"10.1111/xen.12850","url":null,"abstract":"<p><p>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. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 2","pages":"e12850"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159084","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}
Daniel J Hurst, Luz Padilla, Daniel Rodger, Tamar Schiff, David K C Cooper
{"title":"Close contacts of xenograft recipients: Ethical considerations due to risk of xenozoonosis.","authors":"Daniel J Hurst, Luz Padilla, Daniel Rodger, Tamar Schiff, David K C Cooper","doi":"10.1111/xen.12847","DOIUrl":"10.1111/xen.12847","url":null,"abstract":"<p><p>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. This paper examines the ethical and logistical issues raised by the potential exposure to xenozoonotic disease faced by close contacts of xenotransplant recipients-defined herein as including but not limited to caregivers, household contacts, and sexual partners-which warrants special attention given their increased risk of exposure to infection compared to the general public. We discuss implications of assent or consent by these close contacts to potentially undergo, along with the recipient, procedures for infection screening and possible quarantine. We then propose several options and recommendations for operationalizing oversight of xenotransplantation clinical trials that could account for and address close contacts' education on and agency regarding the risk of xenozoonosis.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 2","pages":"e12847"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102524","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 at 30 years - A personal reminiscence and some thoughts for the future.","authors":"David H Sachs","doi":"10.1111/xen.12846","DOIUrl":"10.1111/xen.12846","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"31 2","pages":"e12846"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094645","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}
Bahar Aslan Dogan, Gurkan Ozden, Sevim Dolu, Mesut Mese, Sami Akbulut
{"title":"Evaluation of knowledge, attitude, and awareness of liver transplant patients toward xenotransplantation","authors":"Bahar Aslan Dogan, Gurkan Ozden, Sevim Dolu, Mesut Mese, Sami Akbulut","doi":"10.1111/xen.12844","DOIUrl":"https://doi.org/10.1111/xen.12844","url":null,"abstract":"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).","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"77 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968650","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":"A study of knowledge and acceptance of kidney xenotransplantation among Chinese kidney transplant recipients and candidates","authors":"Yuhao Tu, Xiangli Zhao, Gang Chen, Lan Zhu","doi":"10.1111/xen.12843","DOIUrl":"https://doi.org/10.1111/xen.12843","url":null,"abstract":"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. This study aims to investigate the level of comprehension and acceptance of kidney xenotransplantation in kidney transplant recipients and explore related factors, providing a reference for promoting the application and clinical trials of xenotransplantation in the near future.","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"49 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968412","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":"Pressing ethical issues relating to clinical pig organ transplantation studies","authors":"Daniel J. Hurst, David K. C. Cooper","doi":"10.1111/xen.12848","DOIUrl":"https://doi.org/10.1111/xen.12848","url":null,"abstract":"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. We discuss why it is important and urgent to achieve consensus on these ethical issues prior to carrying out further expanded access experiments or initiating formal clinical trials. The ways forward on each issue are proposed.","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"1 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968756","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}
Martin Bender, Alessandro Panelli, Bruno Reichart, Julia Radan, Maren Mokelke, Elisabeth Neumann, Ines Buttgereit, Sebastian Michel, Andreas Bauer, Ann Kathrin Fresch, Tanja Mayr, Fabian Werner, Stefanie Egerer, Andrea Bähr, Barbara Kessler, Nikolai Klymiuk, David Ayares, Eckhard Wolf, Christian Hagl, Paolo Brenner, Matthias Längin, Jan-Michael Abicht
{"title":"Hemodynamics in pig-to-baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth","authors":"Martin Bender, Alessandro Panelli, Bruno Reichart, Julia Radan, Maren Mokelke, Elisabeth Neumann, Ines Buttgereit, Sebastian Michel, Andreas Bauer, Ann Kathrin Fresch, Tanja Mayr, Fabian Werner, Stefanie Egerer, Andrea Bähr, Barbara Kessler, Nikolai Klymiuk, David Ayares, Eckhard Wolf, Christian Hagl, Paolo Brenner, Matthias Längin, Jan-Michael Abicht","doi":"10.1111/xen.12841","DOIUrl":"https://doi.org/10.1111/xen.12841","url":null,"abstract":"Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth.","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"5 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559220","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}