XenotransplantationPub Date : 2023-03-01Epub Date: 2023-02-28DOI: 10.1111/xen.12796
Mohamed B Ezzelarab, Hidetaka Hara, David Ayares, David K C Cooper
{"title":"Systemic inflammation in the xenotransplant recipient (SIXR) can occur in the absence of pCMV infection.","authors":"Mohamed B Ezzelarab, Hidetaka Hara, David Ayares, David K C Cooper","doi":"10.1111/xen.12796","DOIUrl":"10.1111/xen.12796","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 2","pages":"e12796"},"PeriodicalIF":3.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9581487","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":"Xenotransplantation of pig islet cells: Potential adverse impact of virus infections on their functionality and insulin production.","authors":"Joachim Denner","doi":"10.1111/xen.12789","DOIUrl":"https://doi.org/10.1111/xen.12789","url":null,"abstract":"alle-viate","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 2","pages":"e12789"},"PeriodicalIF":3.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9793043","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}
XenotransplantationPub Date : 2023-03-01Epub Date: 2023-02-23DOI: 10.1111/xen.12795
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
{"title":"Assessment of glomerular filtration and tubular secretion in baboons with life-supporting pig kidney grafts.","authors":"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","doi":"10.1111/xen.12795","DOIUrl":"10.1111/xen.12795","url":null,"abstract":"<p><p>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 a pig-to-baboon renal transplant model. A short IV infusion of inulin and cefoxitin were followed by a maintenance IV infusion of inulin over 5 h in seven healthy baboons, three healthy pigs, and five baboons after bilateral native nephrectomy and intra-abdominal pig renal transplantation. Blood and urine samples were collected. Serum and urinary inulin and serum cefoxitin concentrations measured by validated assays were used to calculate GFR and renal secretion. GFR calculated were similar by both methods. The body weight normalized total body clearance of inulin was similar in pigs and baboons despite differences in absolute clearances. Pig kidney transplanted into baboons provided similar clearance in baboons when normalized to baboon body weight and sustained filtration and secretory functions. The study documented that pig kidneys support the physiologic needs of baboons and are likely to support human recipients as well.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 2","pages":"e12795"},"PeriodicalIF":3.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198977","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}
Karen L Seeberger, Bassem F Salama, Sandra Kelly, Mandy Rosko, Chelsea Castro, Jessica DesAulniers, Gregory S Korbutt
{"title":"Heterogenous expression of endocrine and progenitor cells within the neonatal porcine pancreatic lobes-Implications for neonatal porcine islet xenotransplantation.","authors":"Karen L Seeberger, Bassem F Salama, Sandra Kelly, Mandy Rosko, Chelsea Castro, Jessica DesAulniers, Gregory S Korbutt","doi":"10.1111/xen.12793","DOIUrl":"https://doi.org/10.1111/xen.12793","url":null,"abstract":"<p><p>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 this study we are the first to evaluate all three neonatal porcine pancreatic lobes and NPIs isolated from these lobes. We report, a significant difference in endocrine and progenitor cell composition between lobes, and observed pancreatic duct glands (PDG) within the mesenchyme surrounding exocrine ducts in the DL and CL. Following in vitro differentiation, NPIs isolated from each lobe differed significantly in the percent increase of endocrine cells and final cell composition. Compared to other recipients, diabetic immunodeficient mice transplanted with NPIs isolated from the SL demonstrated euglycemic control as early as 4 weeks (p < 0.05) and achieved normoglycemia by 6 weeks post-transplant (p < 0.01). For the first time we report significant differences between the neonatal porcine pancreatic lobes and demonstrate that NPIs from these lobes differ in xenograft function.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 2","pages":"e12793"},"PeriodicalIF":3.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9495081","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 birth of Dolly and xenotransplantation 25 years on.","authors":"Mark B Nottle, Wayne J Hawthorne, Peter J Cowan","doi":"10.1111/xen.12782","DOIUrl":"https://doi.org/10.1111/xen.12782","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 1","pages":"e12782"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10825898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel J Garry, Joshua I Weiner, Sarah M Greising, David H Sachs, Mary G Garry
{"title":"Xenotransplantation and exotransplantation: Strategies to expand the number of donor organs.","authors":"Daniel J Garry, Joshua I Weiner, Sarah M Greising, David H Sachs, Mary G Garry","doi":"10.1111/xen.12786","DOIUrl":"https://doi.org/10.1111/xen.12786","url":null,"abstract":"<p><p>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 potential to provide an unlimited number of organs for chronic, terminal diseases.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 1","pages":"e12786"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9370584","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}
Christopher Bobier, Daniel Rodger, Daniel J Hurst, Adam Omelianchuk
{"title":"In defense of xenotransplantation research: Because of, not in spite of, animal welfare concerns.","authors":"Christopher Bobier, Daniel Rodger, Daniel J Hurst, Adam Omelianchuk","doi":"10.1111/xen.12791","DOIUrl":"https://doi.org/10.1111/xen.12791","url":null,"abstract":"<p><p>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 species barrier, in addition to the costs borne by non-human animals, has led some to question the value of xenotransplantation altogether. In response, we defend the value of xenotransplantation research, because it can satisfy stringent welfare conditions on the permissibility of animal research and use. Along the way, we respond to the alleged concerns, and conclude that they do not currently warrant a cessation or a curtailing of xenotransplantation research.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 1","pages":"e12791"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831646","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}
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
{"title":"Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets.","authors":"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","doi":"10.1111/xen.12787","DOIUrl":"https://doi.org/10.1111/xen.12787","url":null,"abstract":"<p><strong>Objective: </strong>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 and transplantation. Meanwhile, we explored a new site for xenogeneic islet transplantation in mice.</p><p><strong>Method: </strong>We synthesized a hydrogel combining alginate plus poly-ethylene-imine (Alg/PEI) for the encapsulation of rat, neonatal porcine, and human islets. Transplantation was performed into the retroperitoneal retro-colic space of diabetic mice. Control mice received free islets under the kidney capsule or encapsulated islets into the peritoneum. The biochemical indexes were measured, and the transplanted islets were harvested for immunohistochemical staining of insulin and glucagon.</p><p><strong>Results: </strong>Mice receiving encapsulated rat, porcine and human islets transplanted into the retroperitoneal space maintained normoglycemia for a median of 275, 145.5, and 146 days, respectively. In contrast, encapsulated xenogeneic islets transplanted into the peritoneum, maintained function for a median of 61, 95.5, and 82 days, respectively. Meanwhile, xenogeneic islets transplanted free into the kidney capsule lost their function within 3 days after transplantation. Immunohistochemical staining of encapsulated rat, porcine and human islets, retrieved from the retroperitoneal space, allowed to distinguish morphological normal insulin expressing β- and glucagon expressing α-cells at 70, 60, and 100 days post-transplant, respectively.</p><p><strong>Conclusion: </strong>Transplantation of Alg/PEI encapsulated xenogeneic islets into the retroperitoneal space provides a valuable new implantation strategy for the treatment of type 1 diabetes.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 1","pages":"e12787"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10813850","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":"Systemic inflammation in xenograft recipients (SIXR) or undetected PCMV/PRV transmission?","authors":"Joachim Denner","doi":"10.1111/xen.12788","DOIUrl":"https://doi.org/10.1111/xen.12788","url":null,"abstract":"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 andpromotesactivationofcoagulationafterpig-to-nonhumanprimate xenotransplantation, irrespective of immunosuppressive therapy. 3 Inflammation can be described as a complex biological response of an organism to harmful stimuli and chronic inflammation is observed in various diseases, for example, diabetes, infection, or atherosclerosis. 4 Inflammationisassociatedwiththereleaseofawiderangeofcytokines and chemokines, recruiting immune cells to the site of inflammation and modulating the maturation of immune cells. Among these molecules are tumor necrosis factor (TNF) and interleukin 6 (IL-6), which are highly elevated in animals with SIXR. 5 Innate immune cells expressing tissue factor (TF) are activated after xenotransplantation and expression of the TF by activated endothelial cells is an initial mechanism in the development of thrombotic microangiopathy in the transplant and consumptive coagulopathy (CC) in the recipient. 3,6 Thrombotic microangiopathy and CC are characteristic features asso-ciatedwithxenotransplantfailure. 7,8 TNF-alpha 9 andIL-6 10","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"30 1","pages":"e12788"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9810072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Xenotransplantation: Ethical, Regulatory, and Social Aspects","authors":"","doi":"10.1007/978-3-031-29071-8","DOIUrl":"https://doi.org/10.1007/978-3-031-29071-8","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"1 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50988037","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}