Xenotransplantation最新文献

{"title":"A message from Mr. David Bennett Jr., the son of the first patient to receive a gene-edited pig heart transplant.","authors":"David Bennett","doi":"10.1111/xen.12839","DOIUrl":"10.1111/xen.12839","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 6","pages":"e12839"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804428","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":"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.","authors":"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","doi":"10.1111/xen.12826","DOIUrl":"10.1111/xen.12826","url":null,"abstract":"<p><p>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 systemic immune suppression. In this pilot study, we examined the impact of the CXCL12 micro encapsulant on the function and inflammatory and immune responses of xenogeneic islets transplanted into the omental tissue bilayer sac (OB; n = 4) and diabetic (n = 1) NHPs. Changes in the expression of cytokines after implantation were limited to 2-6-fold changes in blood, most of which did not persist over the first 4 weeks after implantation. Flow cytometry of PBMCs following transplantation showed minimal changes in IFNγ or TNFα expression on xenoantigen-specific CD4⁺  or CD8⁺  T cells compared to unstimulated cells, and these occurred mainly in the first 4 weeks. Microbeads were readily retrievable for assessment at day 90 and day 180 and at retrieval were without microscopic signs of degradation or foreign body responses (FBR). In vitro and immunohistochemistry studies of explanted microbeads indicated the presence of functional xenogeneic islets at day 30 post transplantation in all biopsied NHPs. These results from a small pilot study revealed that CXCL12-microencapsulated xenogeneic islets abrogate inflammatory and adaptive immune responses to the xenograft. This work paves the way toward future larger scale studies of the transplantation of alginate microbeads with CXCL12 and porcine or human stem cell-derived beta cells or allogeneic islets into diabetic NHPs without systemic immunosuppression.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":"e12826"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10242269","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":"Development of a panel for detection of pathogens in xenotransplantation donor pigs.","authors":"Hikari Otabi, Hiroto Miura, Haruka Uryu, Rana Kobayashi-Harada, Kanako Abe, Kazuaki Nakano, Kazuhiro Umeyama, Koki Hasegawa, Takamitsu Tsukahara, Hiroshi Nagashima, Ryo Inoue","doi":"10.1111/xen.12825","DOIUrl":"10.1111/xen.12825","url":null,"abstract":"<p><p>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 can infect to the human host or cause disease in transplanted porcine organs/cells has not been fully defined. In the present study, we thus aimed to develop a larger panel for the detection of pathogens that could potentially infect xenotransplantation donor pigs. Our newly developed panel, which consisted of 76 highly sensitive PCR detection assays, was able to detect 41 viruses, 1 protozoa, and a broad range of bacteria (by use of universal 16S rRNA primers). The applicability of this panel was validated using blood samples from uterectomy-born piglets, and pathogens suspected to be vertically transmitted from sows to piglets were successfully detected. We estimate that, at least for viruses and bacteria, the number of target pathogens detected by the developed screening panel should suffice to meet the microbiological safety levels required worldwide for xenotransplantation and/or regenerative therapy. This panel provides greater diagnosis options to produce donor pigs so that it would render unnecessary to screen for all pathogens listed. Instead, the new panel could be utilized to detect only required pathogens within a given geographic range where the donor pigs for xenotransplantation have been and/or are being developed.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":"e12825"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138219","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":"Lessons learned from the first cardiac xenotransplant in a consciously consenting human: Psychiatric considerations and the impact of media exposure.","authors":"Nithya Cherukuru, Argyro Athanasiadi, Rachel LeMalefant, David Mancini, Anique Forrester, David Glovinsky, Pinar Miski, Catherine Harrison-Restelli, Charles Robinson","doi":"10.1111/xen.12830","DOIUrl":"10.1111/xen.12830","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":"e12830"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682899","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":"Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood.","authors":"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","doi":"10.1111/xen.12828","DOIUrl":"10.1111/xen.12828","url":null,"abstract":"<p><p>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 study was to evaluate the impact of transgenic hTBM expression on the coagulation dysregulation that is observed in association with lung xenograft injury in an established lung perfusion model, with and without additional blockade of nonphysiologic interactions between pig vWF and human GPIb axis. Expression of hTBM was variable between pigs at the transcriptional and protein level. hTBM increased the activation of human protein C and inhibited thrombosis in an in vitro flow perfusion assay, confirming that the expressed protein was functional. Decreased platelet activation was observed during ex vivo perfusion of GalTKO.hCD46 lungs expressing hTBM and, in conjunction with transgenic hTBM, blockade of the platelet GPIb receptor further inhibited platelets and increased survival time. Altogether, our data indicate that expression of transgenic hTBM partially addresses coagulation pathway dysregulation associated with pig lung xenograft injury and, in combination with vWF-GP1b-directed strategies, is a promising approach to improve the outcomes of lung xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":" ","pages":"e12828"},"PeriodicalIF":3.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41136724","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":"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":" ","pages":"e12829"},"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":" ","pages":"e12832"},"PeriodicalIF":3.3,"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":" ","pages":"e12813"},"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":" ","pages":"e12824"},"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":" ","pages":"e12823"},"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}