Xenotransplantation最新文献

{"title":"Meeting report: Xenotransplantation Development Conference in Neijiang, China.","authors":"Guoli Huai, Henk-Jan Schuurman, David K C Cooper, Léo H Bühler, Shaoping Deng, Dengke Pan","doi":"10.1111/xen.12829","DOIUrl":"10.1111/xen.12829","url":null,"abstract":"<p><p>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 to the requirements for designated pathogen-free (DPF) pig facilities and regulation of xenotransplantation. This conference served as an opportunity to collectively advance the development of xenotransplantation in China and pave the way for its clinical application.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41153853","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":"In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys.","authors":"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","doi":"10.1111/xen.12832","DOIUrl":"10.1111/xen.12832","url":null,"abstract":"<p><p>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. Autografts (n = 5) survived throughout the 28 days of follow-up without histopathological features of rejection. Median survival of allografts (n = 6) was 14 days and of pig xenografts (n = 12) 21 days. Allotransplantation was associated with an increase in anti-monkey IgM, but the anticipated subsequent rise in IgG had not yet occurred at the time of euthanasia. Pig grafts were associated with increases in anti-pig IgM and IgG. In all cases, histopathologic features of rejection were similar. 9-GM pig skin xenografts survive at least as long as monkey skin allografts (and trended to survive longer), suggesting that they are a realistic clinical option for the temporary treatment of burns. Although monkeys with pig skin grafts developed anti-pig IgM and IgG antibodies, these did not cross-react with monkey antigens, indicating that a primary 9-GM pig skin graft would not be detrimental to a subsequent monkey skin allograft.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49692693","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":"Acceptance of xenotransplantation by patients waiting for organ donation: A qualitative study.","authors":"Özlem Şahin Akboğa,&nbsp;Akarsu Rukiye Hobek","doi":"10.1111/xen.12813","DOIUrl":"10.1111/xen.12813","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the acceptance and barriers to xenotransplantation in patients waiting for organ transplantation.</p><p><strong>Methods: </strong>It is qualitative and descriptive research. It was completed with 18 patients receiving treatment and waiting for organ transplantation in a dialysis center located in the inner region of Turkey between January 26, 2023 and February 3, 2023. Data were collected with an introductory information form and a semi-structured interview form. The research data were collected through face-to-face in-depth interviews. The content analysis method was used to analyze the data. In line with the goal of reaching data saturation, in-depth interviews were conducted with 18 participants who were open to communication.</p><p><strong>Results: </strong>Two main themes, \"Values\" and \"Thoughts\", and five sub-themes, \"social and religious values, positive, negative and future thoughts\", were identified. Thirteen codes were created including \"not being understood by the society, xenotransplantation prejudice, fear of ridicule and exclusion, religious pressure, desire for unconditional acceptance/rejection\" and \"thought of survival, hope, thought of sinning, submission to doctors, the attitude of religious men and excessive demand\".</p><p><strong>Conclusions: </strong>Patients awaiting organ transplantation need religious, social, and community support for xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9867688","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":"Modeling human anti-pig xenoimmune responses in a pig artery tissue grafted humanized mouse model.","authors":"Minghui Fang,&nbsp;Jun Zou,&nbsp;Fei Xu,&nbsp;Xue Wang,&nbsp;Shucheng Hua,&nbsp;Qi Zhou,&nbsp;Yong-Guang Yang,&nbsp;Zheng Hu","doi":"10.1111/xen.12824","DOIUrl":"10.1111/xen.12824","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Pig artery tissues (PAT) were transplanted into human immune system (HIS) mice or immunodeficient NSG mice (as controls). Intragraft human immune cell infiltration and antibody deposition were quantified using histology and immunohistochemistry. Donor antigen-specific immune responses were quantified using a mixed lymphocyte reaction and a complement-dependent killing assay.</p><p><strong>Results: </strong>Pig CD31⁺ ECs were detected and increased 2-fold from weeks 3 to 5 in PAT xenografts from immunodeficient NSG mice. However, compared with NSG mice, PAT xenografts in HIS mice had significantly lower numbers of porcine CD31⁺ ECs and showed a marked reduction from week 3 to week 5. PAT xenograft rejection in HIS mice is associated with intensive infiltration of human immune cells, deposition of human IgM and IgG antibodies, and the formation of a tertiary lymphoid structure. Robust donor pig antigen-specific human T cells and antibody responses were detected in PAT-transplanted HIS mice.</p><p><strong>Conclusion: </strong>We have developed a humanized mouse model to evaluate human anti-pig xenoimmune responses by PAT transplantation in vivo. This model is expected to facilitate the refinement of pig gene-editing strategies (the expression on EC surface) and the testing of local immunosuppressive strategies for clinical pig organ xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10200810","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":"Organ xenotransplantation acceptance in veterinary students: A multicentric opinion study in Spain.","authors":"Laura Martínez-Alarcón,&nbsp;Juan Flores-Medina,&nbsp;Guillermo Ramis,&nbsp;Jaime Gómez-Laguna,&nbsp;Xavier Moll,&nbsp;Victoria Falceto,&nbsp;Fidel San Román-Ascaso,&nbsp;Fidel San Román-Llorens,&nbsp;Juan José Quereda,&nbsp;Juan Manuel Herrero,&nbsp;Livia Mendonça,&nbsp;José Luis Martin-Barrasa,&nbsp;Olga María Fernández,&nbsp;Antonio Muñoz,&nbsp;Pablo Ramírez,&nbsp;Pedro Gutiérrez,&nbsp;Isabel López-Chicheri,&nbsp;Ana López-Navas,&nbsp;Antonio Ríos","doi":"10.1111/xen.12823","DOIUrl":"10.1111/xen.12823","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>(a) to analyze the attitudes of Veterinary Degree students in six Spanish Universities towards xenotransplantation; and (b) to determine the factors that affect its acceptance.</p><p><strong>Methods: </strong>Of the 2815 students surveyed in the degree program, 2683 valid surveys were obtained. Attitudes towards organ xenotransplantation were evaluated using a validated questionnaire of organ donation.</p><p><strong>Results: </strong>If xenotransplantation was confirmed as a clinical reality, 93% (n = 2493) of those surveyed would accept a xenotransplanted organ, whilst 7% would not. If the results of xenotransplantation were worse than those obtained with human donors and it entailed more risk, 12% (n = 318) would be in favor. 56% (n = 1497) of the students would accept a xenotransplantation provisionally pending the arrival of a human organ. Attitudes towards xenotransplantation were affected by the academic year in which a student was studying, with more favorable attitudes among students in the last year (88% in first year vs. 95% in fifth year; p < .001). More favorable attitudes are also observed depending on the attitude they have towards organ transplantation, with those students being more in favor of donating their organs when they die (94% vs. 88%; p < .001).</p><p><strong>Conclusion: </strong>Veterinary students would have a very favorable attitude toward xenotransplantation if these animal organs functioned as well as human organs. Therefore, these students could play an important role in the future promotion of this technique.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10571268","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":"Expert opinion on the identification, risk assessment, and mitigation of microorganisms and parasites relevant to xenotransplantation products from pigs.","authors":"Huybert Groenendaal,&nbsp;Solenne Costard,&nbsp;Reid Ballard,&nbsp;Stephen Bienhoff,&nbsp;Diana C Challen,&nbsp;Brandon J Dominguez,&nbsp;Douglas R Kern,&nbsp;Dan Miller,&nbsp;Jeske Noordergraaf,&nbsp;Larisa Rudenko,&nbsp;Henk-Jan Schuurman,&nbsp;Tom Spizzo,&nbsp;Matthew Sturos,&nbsp;Bill Zollers,&nbsp;Jay A Fishman","doi":"10.1111/xen.12815","DOIUrl":"10.1111/xen.12815","url":null,"abstract":"<p><p>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 identified 255 MP to include in the risk assessment. These were rated by experts for five criteria regarding potential swine exposure in the USA and human health risks. MP were subsequently categorized into three risk mitigation groups according to pre-defined rules: disqualifying porcine MP (due to their pathogenic potential, n = 130); non-disqualifying porcine MP (still relevant to consider for biosecurity or monitoring efforts, n = 40); and alert/watch list (not reported in the USA or MP not in swine, n = 85). Most disqualifying (n = 126) and non-disqualifying (n = 36) porcine MP can effectively be eliminated with high biosecurity programs. This approach supports surveillance and risk mitigation strategies for porcine MP in swine produced for xenotransplantation, such as documentation of freedom from porcine MP, or use of porcine MP screening, monitoring, or elimination options. To the authors' knowledge, this is the first effort to comprehensively identify all relevant porcine MP systematically and transparently evaluate the risk of infection of both donor animals and immunosuppressed human recipients, and the potential health impacts for immunosuppressed human recipients from infected xenotransplantation products from pigs.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067984","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":"Auxiliary liver xenotransplantation technique in a transgenic pig-to-non-human primate model: A surgical approach to prolong survival.","authors":"Kyo Won Lee,&nbsp;Sean S W Park,&nbsp;Dong Suk Kim,&nbsp;Kimyung Choi,&nbsp;Joohyun Shim,&nbsp;Jihun Kim,&nbsp;Sung Joo Kim,&nbsp;Jae Berm Park","doi":"10.1111/xen.12814","DOIUrl":"10.1111/xen.12814","url":null,"abstract":"<p><p>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. Fifteen consecutive liver xenotransplants were carried out in a pig-to-cynomolgus model. Right auxiliary technique was implemented in two cases, orthotopic in eight cases, and left auxiliary in five cases. None of the right auxiliary recipients survived after surgery due to hemorrhage during complex dissection between the primate's right lobe and inferior vena cava. Orthotopic recipients survived less than 7 days secondary to profound thrombocytopenia and coagulopathy. Two out of five left auxiliary xenotransplants survived more than 3 weeks without uncontrolled thrombocytopenia or anemia, with one of them surviving 34 days, the longest graft survival reported to date. Left auxiliary xenotransplant is a feasible approach in non-human primate experiments, and the feared risk of thrombocytopenia and coagulopathy can be minimized. This may allow for longer evaluation of the xenograft and help better understand histopathological and immunological changes that occur following liver xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870619","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":"Glycocalyx dynamics and the inflammatory response of genetically modified porcine endothelial cells.","authors":"Anastasia Milusev,&nbsp;Jianfang Ren,&nbsp;Alain Despont,&nbsp;Jane Shaw,&nbsp;Matthias Längin,&nbsp;Martin Bender,&nbsp;Jan-Michael Abicht,&nbsp;Maren Mokelke,&nbsp;Julia Radan,&nbsp;Elisabeth Neumann,&nbsp;Elisabeth Kemter,&nbsp;Nikolai Klymiuk,&nbsp;David Ayares,&nbsp;Eckhard Wolf,&nbsp;Bruno Reichart,&nbsp;Nicoletta Sorvillo,&nbsp;Robert Rieben","doi":"10.1111/xen.12820","DOIUrl":"10.1111/xen.12820","url":null,"abstract":"<p><p>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 modification has not been investigated on a cellular level yet. Endothelial cells (EC) and their sugar-rich surface known as the glycocalyx are the first barrier encountering the recipient's immune system, making them a target for rejection. We have previously shown that wild type venous but not arterial EC were protected against heparan sulfate (HS) shedding after activation with human serum or human tumor necrosis factor alpha (TNF𝛼). Using a 2D microfluidic system we investigated the glycocalyx dynamics of genetically modified porcine arterial and venous EC (Gal𝛼1,3 Gal knock-out, transgenic for human CD46 and thrombomodulin, GTKO/hCD46/hTM) after activation with human serum or human TNF𝛼. Interestingly, we observed that GTKO/hCD46/hTM arterial cells, additionally to venous cells, do not shed HS. Unscathed HS on GTKO/hCD46/hTM EC correlated with reduced complement deposition, suggesting that protection against complement activation contributes to maintaining an intact glycocalyx layer on arterial EC. This protection was lost on GTKO/hCD46/hTM cells after simultaneous perfusion with human serum and human TNF𝛼. HS shedding on arterial cells and increased complement deposition on both arterial and venous cells was observed. These findings suggest that GTKO/hCD46/hTM EC revert to a proinflammatory phenotype in an inflammatory xenotransplantation setting, potentially favoring transplant rejection.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41149992","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":"Transplantation of porcine adrenal spheroids for the treatment of adrenal insufficiency.","authors":"Maria Malyukov,&nbsp;Evgeny Gelfgat,&nbsp;Gerard Ruiz-Babot,&nbsp;Janine Schmid,&nbsp;Susann Lehmann,&nbsp;Giatgen Spinas,&nbsp;Felix Beuschlein,&nbsp;Constanze Hantel,&nbsp;Nicole Reisch,&nbsp;Peter P Nawroth,&nbsp;Stefan R Bornstein,&nbsp;Charlotte Steenblock,&nbsp;Barbara Ludwig","doi":"10.1111/xen.12819","DOIUrl":"10.1111/xen.12819","url":null,"abstract":"<p><p>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, we describe the generation and characterization of primary porcine adrenal spheroids capable of replacing the function of adrenal glands in vivo. Cells within the spheroids morphologically resembled adult adrenocortical cells and synthesized and secreted adrenal steroid hormones in a regulated manner. Moreover, the embedding of the spheroids in alginate led to the formation of cellular elongations of steroidogenic cells migrating centripetally towards the inner part of the slab, similar to zona Fasciculata cells in the intact organ. Finally, transplantation of adrenal spheroids in adrenalectomized SCID mice reversed the adrenal insufficiency phenotype, which significantly improved animals' survival. Overall, such adrenal models could be employed for disease modeling and drug testing, and represent the first step toward potential clinical trials in the future.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9972525","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":"Genetic knockout of porcine GGTA1 or CMAH/GGTA1 is associated with the emergence of neo-glycans.","authors":"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","doi":"10.1111/xen.12804","DOIUrl":"10.1111/xen.12804","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>The N-glycome and glycosphingolipidome of native and decellularized porcine pericardia from wildtype (WT), GGTA1-KO and GGTA1/CMAH-KO pigs were analyzed by multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence detection.</p><p><strong>Results: </strong>We identified biantennary and core-fucosylated N-glycans terminating with immunogenic α-Gal- and α-Gal-/Neu5Gc-epitopes on pericardium of WT pigs that were absent in GGTA1 and GGTA1/CMAH-KO pigs, respectively. Levels of N-glycans terminating with galactose bound in β(1-4)-linkage to N-acetylglucosamine and their derivatives elongated by Neu5Ac were increased in both KO groups. N-glycans capped with Neu5Gc were increased in GGTA1-KO pigs compared to WT, but were not detected in GGTA1/CMAH-KO pigs. Similarly, the ganglioside Neu5Gc-GM3 was found in WT and GGTA1-KO but not in GGTA1/CMAH-KO pigs. The applied detergent based decellularization efficiently removed GSL glycans.</p><p><strong>Conclusion: </strong>Genetic deletion of GGTA1 or GGTA1/CMAH removes specific epitopes providing a more human-like glycosylation pattern, but at the same time changes distribution and levels of other porcine glycans that are potentially immunogenic.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060816","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}