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Close contacts of xenograft recipients: Ethical considerations due to risk of xenozoonosis Xenotransplantation (IF 3.9) Pub Date : 2024-03-12 Daniel J. Hurst, Luz Padilla, Daniel Rodger, Tamar Schiff, David K. C. Cooper
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
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Xenotransplantation at 30 years – A personal reminiscence and some thoughts for the future Xenotransplantation (IF 3.9) Pub Date : 2024-03-11 David H. Sachs
CONFLICT OF INTEREST STATEMENT Dr. Sachs is a Co-Founder and Consultant for ITB-MED.
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The Young Investigator Committee of the International Xenotransplantation Association—Perspective of advancements in the field in 2023 Xenotransplantation (IF 3.9) Pub Date : 2024-02-26 Corbin E. Goerlich, Shani S. Kamberi, Joseph Ladowski, Antonio Citro, Margaret Connolly, Konrad Fischer, Evelyn J. Salvaris, Avneesh K. Singh, Yi Wang, Jeffrey Stern, Raphael P. H. Meier
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
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Evaluation of knowledge, attitude, and awareness of liver transplant patients toward xenotransplantation Xenotransplantation (IF 3.9) Pub Date : 2024-02-26 Bahar Aslan Dogan, Gurkan Ozden, Sevim Dolu, Mesut Mese, Sami Akbulut
BackgroundXenotransplantation (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).MethodsThis descriptive study was conducted between November 2022 and August 2023
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A study of knowledge and acceptance of kidney xenotransplantation among Chinese kidney transplant recipients and candidates Xenotransplantation (IF 3.9) Pub Date : 2024-02-26 Yuhao Tu, Xiangli Zhao, Gang Chen, Lan Zhu
BackgroundIn 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
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Pressing ethical issues relating to clinical pig organ transplantation studies Xenotransplantation (IF 3.9) Pub Date : 2024-02-26 Daniel J. Hurst, David K. C. Cooper
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
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Xenotransplantation literature update March 2023–November 2023 Xenotransplantation (IF 3.9) Pub Date : 2024-02-09 Shani Kamberi, Raphael P. H. Meier
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.
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Porcine embryonic stem cells: An alternative solution for the shortage of human islets to treat type 1 diabetes? Xenotransplantation (IF 3.9) Pub Date : 2024-01-25 Mark B. Nottle, Ivan Vassiliev, Wayne J. Hawthorne, Peter J. Cowan
Transplantation of human embryonic stem cell (ESC) derived beta-like cells and xenotransplantation of porcine islets are two potential cures for type 1 diabetes (T1D). We have previously reported the isolation of porcine ESCs and have also separately shown that islets from genetically modified pigs can effectively cure diabetes in a preclinical baboon model. Here we discuss the possibility of combining
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Hemodynamics in pig-to-baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth Xenotransplantation (IF 3.9) Pub Date : 2024-01-25 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
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
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Alteration of γδ T cell subsets in non-human primates transplanted with GGTA1 gene-deficient porcine blood vessels Xenotransplantation (IF 3.9) Pub Date : 2023-12-19 Sujin Lee, Yun Shin Chung, Kyo Won Lee, Miran Choi, Chung Hee Sonn, Won Jun Oh, Hun Gi Hong, Joohyun Shim, Kimyung Choi, Sung Joo Kim, Jae Berm Park, Tae Jin Kim
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.
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Comparison of methods for the detection of porcine cytomegalovirus/roseolovirus in relation to biosafety monitoring of xenotransplantation products Xenotransplantation (IF 3.9) Pub Date : 2023-12-13 Joachim Denner, Hina Jhelum, Sabrina Hansen, Benedikt B. Kaufer
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
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Xenoreactive antibodies in α-granules of human platelets bind pig liver endothelial cells Xenotransplantation (IF 3.9) Pub Date : 2023-11-16 Christopher Burlak, Zheng Yu Wang, Greg Martens, Jose Estrada, Luz Reyes, Victor Manuel Novara Gennuso, Rodrigo Vianna, Matt Tector, Alfred Joseph Tector
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
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Characterisation of transgenic pigs expressing a human T cell-depleting anti-CD2 monoclonal antibody Xenotransplantation (IF 3.9) Pub Date : 2023-11-13 Evelyn J. Salvaris, Nella Fisicaro, Stephen McIlfatrick, Adwin Thomas, Erin Fuller, Andrew M. Lew, Mark B. Nottle, Wayne J. Hawthorne, Peter J. Cowan
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
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In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys Xenotransplantation (IF 3.9) Pub Date : 2023-10-23 Hidetaka Hara, Jeremy B. Foote, Christophe Hansen-Estruch, Mohamed H. Bikhet, Huy Q. Nguyen, Mariyam Javed, Max Oscherwitz, Dalis E. Collins, David Ayares, Takayuki Yamamoto, Timothy W. King, David K. C. Cooper
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
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Lessons learned from the first cardiac xenotransplant in a consciously consenting human: Psychiatric considerations and the impact of media exposure Xenotransplantation (IF 3.9) Pub Date : 2023-10-21 Nithya Cherukuru, Argyro Athanasiadi, Rachel LeMalefant, David Mancini, Anique Forrester, David Glovinsky, Pinar Miski, Catherine Harrison-Restelli, Charles Robinson
CONFLICT OF INTEREST STATEMENT The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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The impact of IdeS (imlifidase) on allo-specific, xeno-reactive, and protective antibodies in a sensitized rhesus macaque model Xenotransplantation (IF 3.9) Pub Date : 2023-10-21 Isabel DeLaura, Joanna Zikos, Imran J. Anwar, Janghoon Yoon, Joseph Ladowski, Annette Jackson, Koen Van Rompay, Diogo Magnani, Stuart J. Knechtle, Jean Kwun
Highly sensitized patients face many barriers to kidney transplantation, including higher rates of antibody-mediated rejection after HLA-incompatible transplant. IdeS, an endopeptidase that cleaves IgG nonspecifically, has been trialed as desensitization prior to kidney transplant, and successfully cleaves donor-specific antibody (DSA), albeit with rebound.
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Development and characterization of islet-derived mesenchymal stem cells from clinical grade neonatal porcine cryopreserved islets Xenotransplantation (IF 3.9) Pub Date : 2023-10-17 Takeshi Kikuchi, Masuhiro Nishimura, Natsuki Komori, Naho Iizuka, Takeshige Otoi, Shinichi Matsumoto
Porcine tissues display a great potential as donor tissues in xenotransplantation, including cell therapy. Cryopreserving clinical grade porcine tissue and using it as a source for establishing therapeutic cells should be advantageous for transportation and scheduled manufacturing of MSCs. Of note, we previously performed encapsulated porcine islet transplantation for the treatment of unstable type
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Meeting report: Xenotransplantation Development Conference in Neijiang, China Xenotransplantation (IF 3.9) Pub Date : 2023-10-04 Guoli Huai, Henk-Jan Schuurman, David K. C. Cooper, Léo H. Bühler, Shaoping Deng, Dengke Pan
A conference on progress in the development of xenotransplantation in China was held in Neijiang, Sichuan, in May 2023, and was attended by approximately 100 established researchers and trainees. Progress in xenotransplantation research was reviewed by both Chinese and foreign experts. The topics discussed ranged from genetic engineering of pigs and the results of pig-to-nonhuman primate organ transplantation
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Development of a panel for detection of pathogens in xenotransplantation donor pigs Xenotransplantation (IF 3.9) Pub Date : 2023-09-28 Hikari Otabi, Hiroto Miura, Haruka Uryu, Rana Kobayashi-Harada, Kanako Abe, Kazuaki Nakano, Kazuhiro Umeyama, Koki Hasegawa, Takamitsu Tsukahara, Hiroshi Nagashima, Ryo Inoue
There have been high expectations in recent years of using xenotransplantation and regenerative medicine to treat humans, and pigs have been utilized as the donor model. Pigs used for these clinical applications must be microbiologically safe, that is, free of infectious pathogens, to prevent infections not only in livestock, but also in humans. Currently, however, the full spectrum of pathogens that
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Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood Xenotransplantation (IF 3.9) Pub Date : 2023-09-28 Lars Burdorf, Zhuo Gao, Andrea Riner, Evelyn Sievert, Donald G. Harris, Kasinath V. Kuravi, Benson H. Morrill, Zahra Habibabady, Elana Rybak, Siamak Dahi, Tianshu Zhang, Evan Schwartz, Elizabeth Kang, Xiangfei Cheng, Charles T. Esmon, Carol J. Phelps, David L. Ayares, Richard N. Pierson III, Agnes M. Azimzadeh
Thrombomodulin is important for the production of activated protein C (APC), a molecule with significant regulatory roles in coagulation and inflammation. To address known molecular incompatibilities between pig thrombomodulin and human thrombin that affect the conversion of protein C into APC, GalTKO.hCD46 pigs have been genetically modified to express human thrombomodulin (hTBM). The aim of this
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Glycocalyx dynamics and the inflammatory response of genetically modified porcine endothelial cells Xenotransplantation (IF 3.9) Pub Date : 2023-09-21 Anastasia Milusev, Jianfang Ren, Alain Despont, Jane Shaw, Matthias Längin, Martin Bender, Jan-Michael Abicht, Maren Mokelke, Julia Radan, Elisabeth Neumann, Elisabeth Kemter, Nikolai Klymiuk, David Ayares, Eckhard Wolf, Bruno Reichart, Nicoletta Sorvillo, Robert Rieben
Xenotransplantation is a promising approach to reduce organ shortage, while genetic modification of donor pigs has significantly decreased the immunogenic burden of xenotransplants, organ rejection is still a hurdle. Genetically modified pig organs are used in xenotransplantation research, and the first clinical pig-to-human heart transplantation was performed in 2022. However, the impact of genetic
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Open invitation to contribute ideas to a multifaceted approach to ethics in xenotransplantation. Xenotransplantation (IF 3.9) Pub Date : 2023-09-15 Kim Solez,Elisa Gordon,Alton Brad Farris,Lynn Cornell
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Short-term function and immune-protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non-human primates without systemic immune suppression: A pilot study Xenotransplantation (IF 3.9) Pub Date : 2023-09-15 Marinko Sremac, Hao Luo, Hongping Deng, Madeline F. E. Parr, Jessica Hutcheson, Pushkar S. Verde, David A. Alagpulinsa, Jenna Miner Kitzmann, Klearchos K. Papas, Timothy Brauns, James F. Markmann, Ji Lei, Mark C. Poznansky
Replacement of insulin-producing pancreatic beta-cells by islet transplantation offers a functional cure for type-1 diabetes (T1D). We recently demonstrated that a clinical grade alginate micro-encapsulant incorporating the immune-repellent chemokine and pro-survival factor CXCL12 could protect and sustain the integrity and function of autologous islets in healthy non-human primates (NHPs) without
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Organ xenotransplantation acceptance in veterinary students: A multicentric opinion study in Spain Xenotransplantation (IF 3.9) Pub Date : 2023-09-11 Laura Martínez-Alarcón, Juan Flores-Medina, Guillermo Ramis, Jaime Gómez-Laguna, Xavier Moll, Victoria Falceto, Fidel San Román-Ascaso, Fidel San Román-Llorens, Juan José Quereda, Juan Manuel Herrero, Livia Mendonça, José Luis Martin-Barrasa, Olga María Fernández, Antonio Muñoz, Pablo Ramírez, Pedro Gutiérrez, Isabel López-Chicheri, Ana López-Navas, Antonio Ríos
The shortage of available transplant organs has made it necessary to search for alternatives, one of which is xenotransplantation. However, the use of animal organs could face rejection from society and the personnel involved in its implementation. Objectives: (a) to analyze the attitudes of Veterinary Degree students in six Spanish Universities towards xenotransplantation; and (b) to determine the
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Modeling human anti-pig xenoimmune responses in a pig artery tissue grafted humanized mouse model Xenotransplantation (IF 3.9) Pub Date : 2023-09-11 Minghui Fang, Jun Zou, Fei Xu, Xue Wang, Shucheng Hua, Qi Zhou, Yong-guang Yang, Zheng Hu
Blood vessels that contain endothelial cells (ECs) on the surface are in direct contact with host blood and are the first target of xenograft rejection. Currently, our understanding of human anti-pig vessel immune responses is primarily based on in vitro assays using pig ECs. Therefore, it is necessary to develop an animal model that permits in vivo study of human immunological rejection of pig vessels
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COVER IMAGE Xenotransplantation (IF 3.9) Pub Date : 2023-08-24
The cover image is based on the Original Article PCR and peptide based PCMV detection in pig – development and application of a combined testing procedure differentiating newly from latent infected pigs by Nicole Fischer et al., https://doi.org/10.1111/xen.12803.
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Expert opinion on the identification, risk assessment, and mitigation of microorganisms and parasites relevant to xenotransplantation products from pigs Xenotransplantation (IF 3.9) Pub Date : 2023-08-24 Huybert Groenendaal, Solenne Costard, Reid Ballard, Stephen Bienhoff, Diana C. Challen, Brandon J. Dominguez, Douglas R. Kern, Dan Miller, Jeske Noordergraaf, Larisa Rudenko, Henk-Jan Schuurman, Tom Spizzo, Matthew Sturos, Bill Zollers, Jay A. Fishman
Xenotransplantation has the potential to address shortages of organs available for clinical transplantation, but concerns exist regarding potential risks posed by porcine microorganisms and parasites (MP) to the health of human recipients. In this study, a risk-based framework was developed, and expert opinion was elicited to evaluate porcine MP based on swine exposure and risk to human health. Experts
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International Xenotransplantation Association (IXA) 25th anniversary. Xenotransplantation (IF 3.9) Pub Date : 2023-08-21 Leo Buhler,Wayne J Hawthorne
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A murine groin site cardiac transplantation model—applicable tool for studying roles of peripheral lymph nodes in transplantation Xenotransplantation (IF 3.9) Pub Date : 2023-08-07 Yaguang Li, Wenjia Yuan, Mingda Zhong, Julia Qi, Xinguo Zheng, Xubiao Xie, Tengfang Li, Hedong Zhang, Xin Jiang, Longkai Peng, Helong Dai
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
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Transplantation of porcine adrenal spheroids for the treatment of adrenal insufficiency Xenotransplantation (IF 3.9) Pub Date : 2023-08-07 Maria Malyukov, Evgeny Gelfgat, Gerard Ruiz-Babot, Janine Schmid, Susann Lehmann, Giatgen Spinas, Felix Beuschlein, Constanze Hantel, Nicole Reisch, Peter P. Nawroth, Stefan R. Bornstein, Charlotte Steenblock, Barbara Ludwig
Primary adrenal insufficiency is a life-threatening disorder, which requires lifelong hormone replacement therapy. Transplantation of xenogeneic adrenal cells is a potential alternative approach for the treatment of adrenal insufficiency. For a successful outcome of this replacement therapy, transplanted cells should provide adequate hormone secretion and respond to adrenal physiological stimuli. Here
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Antibody-mediated rejection in xenotransplantation: Can it be prevented or reversed? Xenotransplantation (IF 3.9) Pub Date : 2023-08-07 Zahra Habibabady, Gannon McGrath, Kohei Kinoshita, Akihiro Maenaka, Ileka Ikechukwu, Gabriela F. Elias, Tjasa Zaletel, Ivy Rosales, Hidetaka Hara, Richard N. Pierson, David K. C. Cooper
Antibody-mediated rejection (AMR) is the commonest cause of failure of a pig graft after transplantation into an immunosuppressed nonhuman primate (NHP). The incidence of AMR compared to acute cellular rejection is much higher in xenotransplantation (46% vs. 7%) than in allotransplantation (3% vs. 63%) in NHPs. Although AMR in an allograft can often be reversed, to our knowledge there is no report
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Incidence of serum antibodies to xenoantigens on triple-knockout pig cells in different human groups Xenotransplantation (IF 3.9) Pub Date : 2023-08-02 Songzhe He, Tao Li, Hao Feng, Jiaxiang Du, David K. C. Cooper, Hidetaka Hara, Hongtao Jiang, Dengke Pan, Gang Chen, Yi Wang
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.
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Increased human complement pathway regulatory protein gene dose is associated with increased endothelial expression and prolonged survival during ex-vivo perfusion of GTKO pig lungs with human blood Xenotransplantation (IF 3.9) Pub Date : 2023-07-28 Ryan Chaban, Gannon McGrath, Zahra Habibabady, Ivy Rosales, Lars Burdorf, David L. Ayares, Elana Rybak, Tianshu Zhang, Donald G. Harris, Siamak Dahi, Franchesca Ali, Dawn M. Parsell, Gheorghe Braileanu, Xiangfei Cheng, Evelyn Sievert, Carol Phelps, Agnes M. Azimzadeh, Richard N. Pierson
Expression of human complement pathway regulatory proteins (hCPRP's) such as CD46 or CD55 has been associated with improved survival of pig organ xenografts in multiple different models. Here we evaluate the hypothesis that an increased human CD46 gene dose, through homozygosity or additional expression of a second hCPRP, is associated with increased protein expression and with improved protection
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Auxiliary liver xenotransplantation technique in a transgenic pig-to-non-human primate model: A surgical approach to prolong survival Xenotransplantation (IF 3.9) Pub Date : 2023-07-26 Kyo Won Lee, Sean S. W. Park, Dong Suk Kim, Kimyung Choi, Joohyun Shim, Jihun Kim, Sung Joo Kim, Jae Berm Park
Xenotransplantation using pigs' liver offers a potentially alternative method to overcome worldwide donor shortage, or more importantly as a bridge to allotransplantation. However, it has been challenged by profound thrombocytopenia and fatal coagulopathy in non-human primate models. Here we suggest that a left auxiliary technique can be a useful method to achieve extended survival of the xenograft
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Acceptance of xenotransplantation by patients waiting for organ donation: A qualitative study Xenotransplantation (IF 3.9) Pub Date : 2023-07-24 Özlem Şahin Akboğa, Akarsu Rukiye Hobek
The aim of this study was to determine the acceptance and barriers to xenotransplantation in patients waiting for organ transplantation.
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Xenotransplantation literature update March 2021–March 2023 Xenotransplantation (IF 3.9) Pub Date : 2023-05-30 Shani Kamberi, Raphael P.H. Meier
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
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Genetic knockout of porcine GGTA1 or CMAH/GGTA1 is associated with the emergence of neo-glycans Xenotransplantation (IF 3.9) Pub Date : 2023-05-06 Lucrezia Morticelli, Charlotte Rossdam, Samanta Cajic, Dietmar Böthig, Mikhail Magdei, Sugat Ratna Tuladhar, Björn Petersen, Konrad Fischer, Erdmann Rapp, Sotirios Korossis, Axel Haverich, Angelika Schnieke, Heiner Niemann, Falk F. R. Buettner, Andres Hilfiker
Pig-derived tissues could overcome the shortage of human donor organs in transplantation. However, the glycans with terminal α-Gal and Neu5Gc, which are synthesized by enzymes, encoded by the genes GGTA1 and CMAH, are known to play a major role in immunogenicity of porcine tissue, ultimately leading to xenograft rejection.
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Current state of clinical trials on xenograft Xenotransplantation (IF 3.9) Pub Date : 2023-05-05 Jad El Masri, Ahmad Afyouni, Maya Ghazi, Tarek Baroud, Doha Al Majdalany, Aalaa Saleh, Hadi El Assaad, Pascale Salameh
Xenotransplantation is a worth investing branch of science, since it aims to fulfil the demand on human cells, tissues and organs. Despite decades of consistent work in preclinical assessments, clinical trials on xenotransplantation are far from reaching the targeted goal. Our study aims to track the characteristics, assess the content and summarize the plan of each trial on skin, beta-island, bone
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PCR and peptide based PCMV detection in pig – development and application of a combined testing procedure differentiating newly from latent infected pigs Xenotransplantation (IF 3.9) Pub Date : 2023-04-30 Nicole Fischer, Barbara Gulich, Barbara Keßler, Matthias Längin, Jay A. Fishman, Eckhard Wolf, Klaus Boller, Ralf R. Tönjes, Antonia W. Godehardt
Porcine cytomegalovirus (PCMV) is widely distributed in pigs and difficult to detect due to latency. PCMV infection of source pigs was associated with early graft failure after cardiac and renal xenotransplantation into nonhuman primates. Importantly, PCMV infection of the first genetically modified pig heart into a human may have contributed to the reduced survival of the patient. Sensitive and reliable
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First transplantation of a pig heart from a multiple gene-modified donor, porcine cytomegalovirus/roseolovirus, and antiviral drugs Xenotransplantation (IF 3.9) Pub Date : 2023-04-11 Joachim Denner
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, HHV-7), which
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The case for the therapeutic use of mechanistic/mammalian target of rapamycin (mTOR) inhibitors in xenotransplantation Xenotransplantation (IF 3.9) Pub Date : 2023-04-07 Akihiro Maenaka, Kohei Kinoshita, Hidetaka Hara, David K. C. Cooper
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
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Patients’ opinions 10 years after receiving encapsulated porcine islet xenotransplantation without immunosuppression Xenotransplantation (IF 3.9) Pub Date : 2023-04-04 Shinichi Matsumoto, Adrian Abalovich, Shaun Wynyard, Mariana E. Carulla, David Abalovich
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.
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Antibodies against hyaluronan oligosaccharides in xenotransplantation Xenotransplantation (IF 3.9) Pub Date : 2023-03-29 Daniel Bello-Gil, Sara Olivera-Ardid, Alexander B. Tuzikov, Cristina Costa, Nicolai V. Bovin, Rafael Mañez
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
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Xenotransplantation: A historical–ethical account of viewpoints Xenotransplantation (IF 3.9) Pub Date : 2023-03-21 Daniel Rodger, Daniel J. Hurst, David KC Cooper
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
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Attitudes of patients with renal disease on xenotransplantation: A systematic review Xenotransplantation (IF 3.9) Pub Date : 2023-03-07 Isabel DeLaura, Imran J. Anwar, Joseph Ladowski, Alejandra Patino, Sarah Cantrell, Scott Sanoff
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
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Systemic inflammation in the xenotransplant recipient (SIXR) can occur in the absence of pCMV infection. Xenotransplantation (IF 3.9) Pub Date : 2023-02-28 Mohamed B Ezzelarab,Hidetaka Hara,David Ayares,David K C Cooper
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Assessment of glomerular filtration and tubular secretion in baboons with life-supporting pig kidney grafts Xenotransplantation (IF 3.9) Pub Date : 2023-02-23 Christophe Hansen-Estruch, Mohamed H. Bikhet, Imam H. Shaik, Vignesh Vasudevan, Wenchen Zhao, Mariyam Javed, Dalis E. Collins, David Ayares, Eric Judd, David K. C. Cooper, Raman Venkataramanan
With pig kidney xenotransplantation nearing clinical reality, it is imperative to measure pig kidney function in the graft recipients. Our aims were (i) to compare inulin clearance after a short intravenous (IV) bolus with steady-state inulin IV infusion, (ii) to use this method to measure the glomerular filtration rate (GFR), and (iii) to determine the tubular secretory function using cefoxitin in
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Heterogenous expression of endocrine and progenitor cells within the neonatal porcine pancreatic lobes–Implications for neonatal porcine islet xenotransplantation Xenotransplantation (IF 3.9) Pub Date : 2023-02-07 Karen L Seeberger, Bassem F Salama, Sandra Kelly, Mandy Rosko, Chelsea Castro, Jessica DesAulniers, Gregory S Korbutt
Neonatal porcine islets (NPIs) are a source of islets for xenotransplantation. In the pig, the pancreatic lobes remain separate, thus, when optimizing NPI isolation, the pancreatic lobes included in the pancreatic digest should be specified. These lobes are the duodenal (DL), splenic (SL) and connecting (CL) lobe that correspond to the head, body-tail, and uncinate process of the human pancreas. In
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Large-gap peripheral nerve repair using xenogeneic transplants in rhesus macaques Xenotransplantation (IF 3.9) Pub Date : 2023-01-17 Paul Holzer, Elizabeth J. Chang, Kaitlyn Rogers, Jamie Tarlton, Diana Lu, Natasha Gillespie, Jon Adkins, Monica Metea, Alan LaRochelle, Joan Wicks, Buket Onel, Steve Gullans, Joshua C. Doloff, Linda Scobie, Curtis L. Cetrulo, Rod Monroy
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
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In defense of xenotransplantation research: Because of, not in spite of, animal welfare concerns Xenotransplantation (IF 3.9) Pub Date : 2022-12-27 Christopher Bobier, Daniel Rodger, Daniel J. Hurst, Adam Omelianchuk
It is envisioned that one day xenotransplantation will bring about a future where transplantable organs can be safely and efficiently grown in transgenic pigs to help meet the global organ shortage. While recent advances have brought this future closer, worries remain about whether it will be beneficial overall. The unique challenges and risks posed to humans that arise from transplanting across the
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Xenotransplantation of pig islet cells: Potential adverse impact of virus infections on their functionality and insulin production Xenotransplantation (IF 3.9) Pub Date : 2022-12-10 Joachim Denner
Type 1 diabetes is a major health problem throughout the world.1 Xenotransplantation using pig islet cells is under development to alleviate the shortage of human pancreata and human islet cells for the treatment of diabetes. First preclinical and clinical trials were carried out with encouraging results: Transplantation of porcine islets into diabetic non-human primates with immunosuppression showed
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Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets Xenotransplantation (IF 3.9) Pub Date : 2022-12-01 Zhen Geng, Qi Zhang, Ting Li, Ting Huang, Hailian Wang, Qiao Zhou, Shaoping Deng, Yanshuang Zhao, Yanjiao Li, Chunming Cheng, Carmen Gonelle-Gispert, Leo H. Buhler, Yi Wang
Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short-term thrombotic and long-term immune destruction. Meanwhile, the shortage of human organ donors further limits its application. To find a new strategy, we tested a new polymer combination for islet encapsulation
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Patient informed consent for a clinical trial of gene-edited pig kidney transplantation: A representative consent form Xenotransplantation (IF 3.9) Pub Date : 2022-11-26 David K. C. Cooper
When clinical trials of gene-edited pig organ transplantation are initiated, the consent form that the patient is requested to sign will be an important document. Consent to receive a pig xenograft will have significant differences when compared with the requirements of most experimental clinical procedures. We here suggest a consent form for pig kidney transplantation that addresses the major points
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The birth of Dolly and xenotransplantation 25 years on Xenotransplantation (IF 3.9) Pub Date : 2022-11-22 Mark B. Nottle, Wayne J. Hawthorne, Peter J. Cowan
A number of reviews have been written recently celebrating the 25th anniversary of the birth of Dolly the cloned sheep and the effect this breakthrough has had on various fields of research. However, arguably the biggest impact Dolly has had is on the field of xenotransplantation, described here based on our own experience and that of others.
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Systemic inflammation in xenograft recipients (SIXR) or undetected PCMV/PRV transmission? Xenotransplantation (IF 3.9) Pub Date : 2022-11-17 Joachim Denner
Transplantation of pig organs into non-human primates has often been associated with clinical symptoms described as systemic inflammation in xenograft recipients (SIXR).1-4 Systemic inflammation precedes and promotes activation of coagulation after pig-to-nonhuman primate xenotransplantation, irrespective of immunosuppressive therapy.3 Inflammation can be described as a complex biological response
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Xenotransplantation and exotransplantation: Strategies to expand the number of donor organs Xenotransplantation (IF 3.9) Pub Date : 2022-11-11 Daniel J Garry, Joshua I Weiner, Sarah M Greising, David H Sachs, Mary G Garry
Cardiovascular disease is common and has a high mortality. Due to the limited number of organs available for orthotopic heart transplantation, alternative therapies have received intense interest. In this commentary we contrast xenotransplantation and blastocyst complementation to produce pigs that will serve as donors for organ transplantation. These strategies hold tremendous promise and have the
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Early testing of porcine organ xenotransplantation products in humans: Microbial safety as illustrated for porcine cytomegalovirus Xenotransplantation (IF 3.9) Pub Date : 2022-11-06 Joachim Denner, Henk-Jan Schuurman
CONFLICT OF INTEREST Joachim Denner has no conflict of interest. Henk-Jan Schuurman is director at SchuBiomed Consultancy and provides consultancy in the biomedical sector worldwide.
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What is the clinical relevance of deviant serum calcium and phosphate levels after pig-to-primate kidney xenotransplantation? Xenotransplantation (IF 3.9) Pub Date : 2022-10-27 Aaron C. K. Lucander, Eric Judd, David K. C. Cooper
Experience from human renal allotransplantation informs us that disturbances in serum calcium and phosphate levels are relatively common. Post-transplant hypercalcemia is associated with an increased risk of recipient mortality, but not of graft loss or nephropathy, and post-transplant hyperphosphatemia with an increased risk of both recipient mortality and death-censored graft failure, but neither
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Knock-out of N-glycolylneuraminic acid attenuates antibody-mediated rejection in xenogenically perfused porcine lungs Xenotransplantation (IF 3.9) Pub Date : 2022-10-17 Ryan Chaban, Zahra Habibabady, Wessam Hassanein, Margaret R. Connolly, Lars Burdorf, Emily Redding, Christopher Laird, Jolene Ranek, Gheorghe Braileanu, Selin Sendil, Xiangfei Cheng, Wenji Sun, Natalie A. O'Neill, Kasinath Kuravi, Sunghoon Hurh, David L. Ayares, Agnes M. Azimzadeh, Richard N. Pierson
Antibody-mediated rejection has long been known to be one of the major organ failure mechanisms in xenotransplantation. In addition to the porcine α1,3-galactose (α1,3Gal) epitope, N-Glycolylneuraminic acid (Neu5Gc), a sialic acid, has been identified as an important porcine antigen against which most humans have pre-formed antibodies. Here we evaluate GalTKO.hCD46 lungs with an additional cytidine
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Observations on hydronephrosis after pig kidney transplantation in baboons Xenotransplantation (IF 3.9) Pub Date : 2022-09-25 Jeremy B Foote, Mohamed H. Bikhet, Christophe Hansen-Estruch, Mariyam Javed, David Ayares, Hidetaka Hara, Abhinav Humar, Devin E. Eckhoff, David K. C. Cooper
We have seen hydronephrosis (obstructive nephropathy) at necropsy in 3 of 11 (21%) genetically-engineered pig kidneys that functioned in baboons for >36 days, even when the clinical and histopathological features of rejection were minimal. We briefly report one such case and illustrate the macroscopic and microscopic appearances of such a kidney and ureter. The causes of the observed changes remain