Xenotransplantation最新文献

{"title":"A compositional analysis of native and decellularized porcine nasal septum cartilage.","authors":"Katharina Tluczynski,&nbsp;Roman Breiter","doi":"10.1111/xen.12781","DOIUrl":"https://doi.org/10.1111/xen.12781","url":null,"abstract":"<p><strong>Objectives: </strong>Decellularization of porcine septum cartilage is necessary for its application as xenogenic replacement material. The aim of this study was to investigate spatial differences of structure and composition in the whole native and decellularized porcine nasal septum. Subsequently, the results shall be compared with studies of human nasal septum.</p><p><strong>Methods: </strong>Ten porcine nasal septa were divided into six regions from caudal to cephalic and four regions from dorsal to ventral to create a grid of 24 approximately equal segments. All segments of five septal cartilages were decellularized separately by a wet chemical multistep procedure. The segments were analyzed to determine quantitative amounts of total collagen, chondrocytes, and sulfated glycosaminoglycans (sGAG).</p><p><strong>Results: </strong>The distribution of cell number showed no significant differences between the individual regions. For the distribution of collagen and sGAG, no significant differences could be identified from caudal to cephalic, both in native and decellularized tissue. From dorsal to ventral, native and decellularized nasal septum showed significant differences between individual regions. In native septum, linear regression analysis indicated a decreasing collagen and an increasing sGAG content from dorsal to ventral. After decellularization, an increasing collagen and a decreasing sGAG content was detected.</p><p><strong>Conclusion: </strong>The results of this study showed slightly but significant differences in the distribution of collagen and sGAG from dorsal to ventral. From caudal to cephalic, no differences could be observed. Compared to human, nasal septum differences in cell, collagen, and sGAG content were detected. Despite this, human and porcine nasal septum showed similar distributions and a consistently inverse linearity of collagen and sGAG content. Nevertheless, the midcaudal and midcephalic regions showed the highest porosity and a high stability and thus offer the best conditions for the revitalization of porcine tissue by human cells.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089235","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":"Knock-out of N-glycolylneuraminic acid attenuates antibody-mediated rejection in xenogenically perfused porcine lungs.","authors":"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","doi":"10.1111/xen.12784","DOIUrl":"10.1111/xen.12784","url":null,"abstract":"<p><strong>Background: </strong>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 monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene knock-out (Neu5GcKO) in a xenogeneic ex vivo perfusion model METHODS: Eleven GalTKO.hCD46.Neu5GcKO pig lungs were perfused for up to 6 h with fresh heparinized human blood. Six of them were treated with histamine (H) blocker famotidine and 1-thromboxane synthase inhibitor Benzylimidazole (BIA) and five were left untreated. GalTKO.hCD46 lungs without Neu5GcKO (n = 18: eight untreated and 10 BIA+H treated) served as a reference. Functional parameters, blood, and tissue samples were collected at pre-defined time points throughout the perfusion RESULTS: All but one Neu5GcKO organs maintained adequate blood oxygenation and \"survived\" until elective termination at 6 h whereas two reference lungs failed before elective termination at 4 h. Human anti-Neu5Gc antibody serum levels decreased during the perfusion of GalTKO.hCD46 lungs by flow cytometry (∼40% IgM, 60% IgG), whereas antibody levels in Neu5GcKO lung perfusions did not fall (IgM p = .007; IgG p < .001). Thromboxane elaboration, thrombin generation, and histamine levels were significantly reduced with Neu5GcKO lungs compared to reference in the untreated groups (p = .007, .005, and .037, respectively); treatment with BIA+H masked these changes. Activation of platelets, measured as CD62P expression on circulating platelets, was lower in Neu5GcKO experiments compared to reference lungs (p = .023), whereas complement activation (as C3a rise in plasma) was not altered. MCP-1 and lactotransferin level elevations were blunted in Neu5GcKO lung perfusions (p = .007 and .032, respectively). Pulmonary vascular resistance (PVR) rise was significantly attenuated and delayed in untreated GalTKO.hCD46.Neu5GcKO lungs in comparison to the untreated GalTKO.hCD46 lungs (p = .003) CONCLUSION: Additional Neu5GcKO in GalTKO.hCD46 lungs significantly reduces parameters associated with antibody-mediated inflammation and activation of the coagulation cascade. Knock-out of the Neu5Gc sialic acid should be beneficial to reduce innate immune antigenicity of porcine lungs in future human recipients.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516938","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":"Recellularized bovine pericardium with autologous mesenchymal stem cells reduces immune activation.","authors":"Sabin J Bozso,&nbsp;Jimmy J H Kang,&nbsp;Ryaan El-Andari,&nbsp;Dana Boe,&nbsp;Hannah Hedtke,&nbsp;Michael C Moon,&nbsp;Darren H Freed,&nbsp;Jayan Nagendran,&nbsp;Jeevan Nagendran","doi":"10.1111/xen.12774","DOIUrl":"https://doi.org/10.1111/xen.12774","url":null,"abstract":"<p><strong>Introduction: </strong>Current bioprosthetic heart valve replacement options are limited by structural valvular deterioration (SVD) due to an immune response to the xenogenic scaffold. Autologous mesenchymal stem cell (MSC) recellularization is a method of concealing xenogenic scaffolds, preventing recipient immune recognition of xenogenic tissue heart valves, and potentially leading to reduction in SVD incidence. The purpose of this study is to examine the effects of autologous MSC recellularized tissue on the immune response of human whole blood to bovine pericardium (BP). We hypothesized that autologous MSC recellularization of BP will result in reduced pro-inflammatory cytokine production equivalent to autologous human pericardium.</p><p><strong>Methods: </strong>Bone marrow, human pericardium, and whole blood were collected from adult patients undergoing elective cardiac surgery. Decellularized BP underwent recellularization with autologous MSCs, followed by co-incubation with autologous whole blood. Immunohistochemical, microscopic, and quantitative immune analysis approaches were used.</p><p><strong>Results: </strong>We demonstrated that native BP, exposed to human whole blood, results in significant TNF-α and IL1β production. When decellularized BP is recellularized with autologous MSCs and exposed to whole blood, there is a significant reduction in TNF-α and IL1β production. Importantly, recellularized BP exposed to whole blood had similar production of TNF-α and IL1β when compared to autologous human pericardium exposed to human whole blood.</p><p><strong>Conclusion: </strong>Our results suggest that preventing initial immune activation with autologous MSC recellularization may be an effective approach to decrease the recipient immune response, preventing recipient immune recognition of xenogeneic tissue engineered heart valves, and potentially leading to reduction in SVD incidence.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10523245","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":"Observations on hydronephrosis after pig kidney transplantation in baboons.","authors":"Jeremy B Foote,&nbsp;Mohamed H Bikhet,&nbsp;Christophe Hansen-Estruch,&nbsp;Mariyam Javed,&nbsp;David Ayares,&nbsp;Hidetaka Hara,&nbsp;Abhinav Humar,&nbsp;Devin E Eckhoff,&nbsp;David K C Cooper","doi":"10.1111/xen.12779","DOIUrl":"10.1111/xen.12779","url":null,"abstract":"<p><p>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 uncertain. In our small experience, there seems to be no correlation between the development of hydronephrosis and (i) the surgical technique, (ii) the genotype of the pig, (iii) the length of the pig ureter, or (iv) the immunosuppressive and anti-inflammatory therapy administered. We suggest that the distal ureteric thickening may be the result of an inflammatory response. In two cases, we resolved the problem by carrying out a secondary side-to-side anastomosis between the proximal pig ureter and the baboon bladder.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9234127","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":"Early testing of porcine organ xenotransplantation products in humans: Microbial safety as illustrated for porcine cytomegalovirus.","authors":"Joachim Denner,&nbsp;Henk-Jan Schuurman","doi":"10.1111/xen.12783","DOIUrl":"https://doi.org/10.1111/xen.12783","url":null,"abstract":"Sincemid-2021, a number of exploratory studies have been conducted to test porcine solid organs in humans, representing a new step in moving xenotransplantation towards clinical application. These studies are summarized below and attracted wide interest in the media and scientific community, resulting in commentaries in scientific journals (referenced below). We focus in this commentary on safety, that is, the potential of transspecies transmission of infectious agents, in particular viruses.1 Transspecies transmission of endogenous retrovirus, that is, porcineendogenous retrovirus (PERV)hasbeen subject of much research during the last decades; this research resulted, amongst others, in studies using pig donors that are negative for the PERV-C subtype, or in generation of pigs in which PERV-A and PERV-B subtypes were genetically inactivated (on a PERV-C negative platform).2 Although PERV-C infects only pig cells but not human cells, its presence allows recombination between PERV-C and PERV-A, resulting in high titer PERV-A/C recombinants.3 However, such a recombination is a rare event in vivo.4 The item of PERV risk was not addressed in the exploratory studies, and will not be discussed in this manuscript. But, one exogenous virus, porcine cytomegalovirus (PCMV), popped up in","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10526248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1111/xen.12698","DOIUrl":"https://doi.org/10.1111/xen.12698","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41542732","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":"The attitudes of religious group leaders towards xenotransplantation: A focus group study.","authors":"Daniel J Hurst, Luz A Padilla, David Kc Cooper, Wendy Walters, Wayne Paris","doi":"10.1111/xen.12777","DOIUrl":"10.1111/xen.12777","url":null,"abstract":"<p><p>Clinical trials of xenotransplantation (XTx) may start in coming years. Religious views have been mentioned as possible barriers to XTx acceptance. While there have been reports on perspectives of theologians in regard to XTx, no report has studied the perspectives of community religious leaders. A focus group was conducted with a sample of members of the following faith groups: Islam, Catholicism, and Protestantism. Qualitative content analysis was performed to identify interpretive themes. Four themes emerged. Participants were receptive to the idea of XTx and expressed no religious barriers to accepting a pig xenograft as a lifesaving therapy but did express certain concerns. Religious leaders accept the idea of XTx and do not see it as contradictory to their beliefs. However, some concerns were raised. Future studies addressing these concerns and exploring the potential role of religious leaders in educating the community on XTx are needed.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10124762/pdf/nihms-1887527.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10528205","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":"SARS-CoV-2 does not infect pigs, but this has to be verified regularly.","authors":"Tanja Opriessnig,&nbsp;Yao-Wei Huang","doi":"10.1111/xen.12772","DOIUrl":"https://doi.org/10.1111/xen.12772","url":null,"abstract":"<p><p>For successful xenotransplantation, freedom of the xenocraft donor from certain viral infections that may harm the organ recipient is important. A novel human coronavirus (CoV) with a respiratory tropism, designated as SARS-CoV-2, was first identified in January 2020 in China, but likely has been circulating unnoticed for some time before. Since then, this virus has reached most inhabited areas, resulting in a major global pandemic which is still ongoing. Due to a high number of subclinical infections, re-infections, geographic differences in diagnostic tests used, and differences in result reporting programs, the percentage of the population infected with SARS-CoV-2 at least once has been challenging to estimate. With continuous ongoing infections in people and an overall high viral load, it makes sense to look into possible viral spillover events in pets and farm animals, who are often in close contact with humans. The pig is currently the main species considered for xenotransplantation and hence there is interest to know if pigs can become infected with SARS-CoV-2 and if so what the infection dynamics may look like. This review article summarizes the latest research findings on this topic. It would appear that pigs can currently be considered a low risk species, and hence do not pose an immediate risk to the human population or xenotransplantation recipients per se. Monitoring the ever-changing SARS-CoV-2 variants appears important to recognize immediately should this change in the future.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9538518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33446546","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":"Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV): A threat for xenotransplantation?","authors":"Nicolas J Mueller,&nbsp;Joachim Denner","doi":"10.1111/xen.12775","DOIUrl":"https://doi.org/10.1111/xen.12775","url":null,"abstract":"<p><p>The potential for a donor-derived transmission of porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) to the recipient has been recognized since pigs were considered candidate donors for xenotransplantation. This review gives a short description of the viral properties and summarizes the current evidence of the effects of PCMV/PRV transmission in preclinical xenotransplantation. Despite evidence that PCMV/PRV does not infect human and non-human primate cells, activation in the transplanted organ and detrimental systemic complications have been described. As PCMV/PRV is a herpesvirus able to establish latency, the importance of adequate screening of donor pigs is emphasized, as no efficient treatment is available. Furthermore, easy and successful ways of elimination of PCMV/PRV from pig herds are indicated.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33454722","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":"Mathieu Jaboulay's (1860-1913) contribution to xenotransplantation.","authors":"Daniel Rodger, Daniel J Hurst","doi":"10.1111/xen.12765","DOIUrl":"10.1111/xen.12765","url":null,"abstract":"<p><p>Mathieu Jaboulay (1860-1913) was a professor of clinical surgery in Lyon, France who is best known for his development of vascular anastomosis and for conducting the first reported renal xenotransplantation experiments on humans, using pig and goat kidneys to treat end-stage renal failure in 1906. His insights and pioneering techniques contributed significantly to allotransplantation and contemporary attempts at xenotransplantation. He is also credited with inventing several surgical instruments and novel surgical techniques that continue to influence vascular, general, and urological surgery to this day. However, this article will focus specifically on his notable contributions to xenotransplantation research and surgery.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10446463","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}