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Xenotransplantation

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https://www.readbyqxmd.com/read/29782054/assessment-of-porcine-endogenous-retrovirus-transmission-across-an-alginate-barrier-used-for-the-encapsulation-of-porcine-islets
#1
Claire Crossan, Nizar I Mourad, Karen Smith, Pierre Gianello, Linda Scobie
BACKGROUND: Subcutaneous implantation of a macroencapsulated patch containing human allogenic islets has been successfully used to alleviate type 1 diabetes mellitus (T1DM) in a human recipient without the need for immunosuppression. The use of encapsulated porcine islets to treat T1DM has also been reported. Although no evidence of pathogen transfer using this technology has been reported to date, we deemed it appropriate to determine if the encapsulation technology would prevent the release of virus, in particular, the porcine endogenous retrovirus (PERV)...
May 21, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29777547/tacrolimus-induced-asymptomatic-thrombotic-microangiopathy-diagnosed-by-laboratory-tests-in-pig-to-rhesus-corneal-xenotransplantation-a-case-report
#2
Jong-Min Kim, Jaeyoung Kim, Se-Hyun Choi, Jun-Seop Shin, Byoung-Hoon Min, Won Young Jeong, Ga-Eul Lee, Min-Sun Kim, Seeun Kwon, Mee Kum Kim, Chung-Gyu Park
Tacrolimus-associated thrombotic microangiopathy (TA-TMA) is a rare complication. TA-TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage due to thrombus. We report asymptomatic TA-TMA diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation. Corneal transplantation had been conducted from a wild-type SNU miniature pig to a rhesus macaque. The veterinary records were retrospectively reviewed in this case. The immunosuppressive regimen consisted of rituximab, basiliximab, and IVIg as inductive therapies, and steroids with tacrolimus (0...
May 18, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29756410/the-feasibility-and-efficacy-of-preparing-porcine-descemet-s-membrane-endothelial-keratoplasty-dmek-grafts-by-two-techniques-an-ex-vivo-investigation-for-future-xeno-dmek
#3
Yang Liu, Jing Zhang, Yingnan Zhang, Mingyang Yin, Sen Miao, Qingfeng Liang, Zhiqiang Pan
BACKGROUND: Descemet's membrane endothelial keratoplasty (DMEK) might be a promising technique for future xeno-corneal transplantation due to its ultrathin graft, extremely low rejection occurrence, suture-free graft fixation, and minimal immunosuppressive regime usage. The aim of this study is to explore the feasibility and efficacy of preparing porcine DMEK grafts by 2 techniques and investigate the graft ultrastructure. METHODS: Two mainstream techniques, mechanical stripping technique and liquid bubble technique, were modified to prepare the porcine DMEK grafts...
May 13, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29756348/is-it-currently-possible-to-evaluate-the-risk-posed-by-pervs-for-clinical-xenotransplantation
#4
Joachim Denner, Linda Scobie, Henk-Jan Schuurman
No abstract text is available yet for this article.
May 13, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29756309/infection-hazards-of-xenotransplantation-retrospect-and-prospect
#5
Robin A Weiss
No abstract text is available yet for this article.
May 13, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29732615/update-on-cellular-encapsulation
#6
REVIEW
Kate E Smith, Robert C Johnson, Klearchos K Papas
There is currently a significant disparity between the number of patients who need lifesaving transplants and the number of donated human organs. Xenotransplantation is a way to address this disparity and attempts to enable the use of xenogeneic tissues have persisted for centuries. While immunologic incompatibilities have presented a persistent impediment to their use, encapsulation may represent a way forward for the use of cell-based xenogeneic therapeutics without the need for immunosuppression. In conjunction with modern innovations such as the use of bioprinting, incorporation of immune modulating molecules into capsule membranes, and genetic engineering, the application of xenogeneic cells to treat disorders ranging from pain to liver failure is becoming increasingly realistic...
May 6, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29687920/jewish-christian-and-muslim-theological-perspectives-about-xenotransplantation
#7
Wayne Paris, Rabbi Jerry H Seidler, Kevin FitzGerald, Aasim I Padela, Emanuele Cozzi, David K C Cooper
BACKGROUND: This paper is based on a theological symposium presented at the International Xenotransplantation Association's 14th Congress held in Baltimore, MD, September, 2017. METHODS: The information explores the Jewish, Christian and Muslim theological perceptions and perspectives about cross-species (ie pig-to-human) organ transplantation, the genetic alterations required in the organ-source pig, and their potential to influence individual acceptance of the procedure...
April 24, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29655276/is-sensitization-to-pig-antigens-detrimental-to-subsequent-allotransplantation
#8
REVIEW
Qi Li, Hidetaka Hara, Zhongqiang Zhang, Michael E Breimer, Yi Wang, David K C Cooper
An important question in xenotransplantation is whether an allotransplant can safely be carried out in a patient who has become sensitized to a pig xenograft. To answer this question, we have searched the literature. We primarily limited our review to the clinically relevant pig-to-non-human primate (NHP) model and found five studies that explored this topic. No NHP that had received a pig graft developed antibodies to alloantigens, and in vitro studies indicated no increased humoral and/or cellular alloreactivity...
April 14, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29635708/human-cd31-on-porcine-cells-suppress-xenogeneic-neutrophil-mediated-cytotoxicity-via-the-inhibition-of-netosis
#9
Han-Tang Wang, Akira Maeda, Rieko Sakai, Pei-Chi Lo, Chihiro Takakura, Patmika Jiaravuthisan, Afifah Mod Shabri, Rei Matsuura, Tasuku Kodama, Shohei Hiwatashi, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
BACKGROUND: Xenotransplantation is one of the promising strategies for overcoming the shortage of organs available for transplant. However, many immunological obstructions need to be overcome for practical use. Increasing evidence suggests that neutrophils contribute to xenogeneic cellular rejection. Neutrophils are regulated by activation and inhibitory signals to induce appropriate immune reactions and to avoid unnecessary immune reactivity. Therefore, we hypothesized that the development of neutrophil-targeted therapies may have the potential for increased graft survival in xenotransplantation...
April 8, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29624743/absence-of-interaction-between-porcine-endogenous-retrovirus-and-porcine-cytomegalovirus-in-pig-to-baboon-renal-xenotransplantation-in-vivo
#10
Jay A Fishman, David H Sachs, Kazuhiko Yamada, Robert A Wilkinson
BACKGROUND: Studies of xenotransplantation from swine have identified porcine viruses as potential barriers to clinical trials. The biology of these viruses has not been extensively investigated in the in vivo xeno-environment. Enhancement of viral gene expression by viral and cellular factors acting in trans has been demonstrated for certain viruses, including bidirectional interactions between human herpesviruses and endogenous (HERV) and exogenous (HIV) retroviruses. Both porcine cytomegalovirus (PCMV) and porcine endogenous retrovirus (PERV) infections have been identified in xenografts from swine...
April 6, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29604134/b4galnt2-and-xenotransplantation-a-newly-appreciated-xenogeneic-antigen
#11
REVIEW
Guerard Byrne, Saadullah Ahmad-Villiers, Zeji Du, Christopher McGregor
Analysis of non-Gal antibody induced after pig-to-baboon cardiac xenotransplantation identified the glycan produced by porcine beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) as an immunogenic xenotransplantation antigen. The porcine B4GALNT2 enzyme is homologous to the human enzyme, which synthesizes the human SDa blood group antigen. Most humans produce low levels of anti-SDa IgM which polyagglutinates red blood cells from rare individuals with high levels of SDa expression. The SDa glycan is also present on GM2 gangliosides...
March 31, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29582477/immune-molecular-profiling-of-whole-blood-drawn-from-a-non-human-primate-cardiac-xenograft-model-treated-with-anti-cd154-monoclonal-antibodies
#12
Sun A Ock, Keon Bong Oh, Seongsoo Hwang, Ik Jin Yun, Curie Ahn, Hyun Ken Chee, Hwajung Kim, Imran Ullah, Gi-Sun Im, Eung Woo Park
Most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. Here, we performed immune molecular profiling following anti-CD154 monoclonal antibody (mAb) treatment in heterotopic abdominal cardiac xenografts from α-1,3-galactosyltransferase-knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. Blood samples were collected from healthy monkeys as control and then at 2 days after xenograft transplantation and just before humane euthanasia; 94 genes related to the immune system were analyzed...
March 26, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29536572/multiple-genetically-modified-gtko-hcd46-hla-e-h%C3%AE-2-mg-porcine-hearts-are-protected-from-complement-activation-and-natural-killer-cell-infiltration-during-ex-vivo-perfusion-with-human-blood
#13
Jan-Michael Abicht, Riccardo Sfriso, Bruno Reichart, Matthias Längin, Katja Gahle, Gisella L Puga Yung, Jörg D Seebach, Robert Rieben, David Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Baehr, Alexander Kind, Tanja Mayr, Andreas Bauer
BACKGROUND: In pig-to-human xenotransplantation, early cellular rejection reactions are mediated by natural killer cells (NK cells). Human NK cells are inhibited by HLA-E via CD94/NKG2A receptors. To protect porcine grafts against human NK cell responses, transgenic GTKO pigs expressing hCD46 and HLA-E have been generated. The aim of this study was to test the effect of this genetic modification on xenogeneic, and in particular human NK cell response, using an ex vivo perfusion model of pig hearts with human blood...
March 14, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29527745/galt-ko-pig-lungs-are-highly-susceptible-to-acute-vascular-rejection-in-baboons-which-may-be-mitigated-by-transgenic-expression-of-hcd47-on-porcine-blood-vessels
#14
Hironosuke Watanabe, Hisashi Sahara, Shunichiro Nomura, Tatsu Tanabe, Dilrukshi K Ekanayake-Alper, Lennan K Boyd, Nathan J Louras, Arsenoi Asfour, Makenzie A Danton, Siu-Hong Ho, Scott J Arn, Robert J Hawley, Akira Shimizu, Takeshi Nagayasu, David Ayares, Marc I Lorber, Megan Sykes, David H Sachs, Kazuhiko Yamada
BACKGROUND: Despite recent progress in survival times of xenografts in non-human primates, there are no reports of survival beyond 5 days of histologically well-aerated porcine lung grafts in baboons. Here, we report our initial results of pig-to-baboon xeno-lung transplantation (XLTx). METHODS: Eleven baboons received genetically modified porcine left lungs from either GalT-KO alone (n = 3), GalT-KO/humanCD47(hCD47)/hCD55 (n = 3), GalT-KO/hD47/hCD46 (n = 4), or GalT-KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine...
March 12, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29654665/xenotransplantation-literature-update-january-february-2018
#15
Wayne J Hawthorne, Christopher Burlak
No abstract text is available yet for this article.
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29446183/comparison-of-detergent-based-decellularization-protocols-for-the-removal-of-antigenic-cellular-components-in-porcine-aortic-valve
#16
Xiaohong Liu, Ning Li, Dejun Gong, Cuiping Xia, Zhiyun Xu
BACKGROUND: Various detergent-based protocols are used to remove cells and cellular debris in porcine aortic valve (PAV). However, the removal of antigenic cellular components has not been thoroughly elucidated to date. In this study, we used 4 detergent-based protocols to decellularize PAVs and aimed to evaluate their effects on removing antigenic cellular components. METHODS: Porcine aortic valves were decellularized using sodium dodecyl sulfate (SDS), SDS in combination with sodium deoxycholate (SDS/SD), Triton X-100, and Triton X-100 in combination with SD (Triton X-100/SD), respectively...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29430727/the-sda-and-cad-glycan-antigens-and-their-glycosyltransferase-%C3%AE-1-4galnact-ii-in-xenotransplantation
#17
REVIEW
Chengjiang Zhao, David K C Cooper, Yifan Dai, Hidetaka Hara, Zhiming Cai, Lisha Mou
Antibody-mediated rejection is a barrier to the clinical application of xenotransplantation, and xenoantigens play an important role in this process. Early research suggested that N-acetyl-D-galactosamine (GalNAc) could serve as a potential xenoantigen. GalNAc is the immunodominant glycan of the Sda antigen. Recently, knockout of β1,4-N-acetylgalactosaminyltransferase 2 (β1,4GalNAcT-II) from the pig results in a decrease in binding of human serum antibodies to pig cells. It is believed that this is the result of the elimination of the GalNAc on the Sda antigen, which is catalyzed by the enzyme, β1,4GalNAcT-II...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29427404/interleukin-8-mediates-neutrophil-endothelial-interactions-in-pig-to-human-xenogeneic-models
#18
Beth M French, Selin Sendil, Krishna Mohan Sepuru, Jolene Ranek, Lars Burdorf, Donald Harris, Emily Redding, Xiangfei Cheng, Christopher T Laird, Yuming Zhao, Benjamin Cerel, Krishna Rajarathnam, Richard N Pierson, Agnes M Azimzadeh
BACKGROUND: Human neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno-antigens or added human regulatory molecules intended to down-regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin-8 (IL-8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL-8 promote the adhesion of human neutrophils in in vitro xenograft models...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29359469/p-and-e-selectin-receptor-antagonism-prevents-human-leukocyte-adhesion-to-activated-porcine-endothelial-monolayers-and-attenuates-porcine-endothelial-damage
#19
Christopher T Laird, Wessam Hassanein, Natalie A O'Neill, Beth M French, Xiangfei Cheng, William E Fogler, John L Magnani, Dawn Parsell, Arielle Cimeno, Carol J Phelps, David Ayares, Lars Burdorf, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Alongside the need to develop more effective and less toxic immunosuppression, the shortage of human organs available for organ transplantation is one of the major hurdles facing the field. Research into xenotransplantation, as an alternative source of organs, has unveiled formidable challenges. Porcine lungs perfused with human blood rapidly sequester the majority of circulating neutrophils and platelets, which leads to inflammation and organ failure within hours, and is not significantly attenuated by genetic modifications to the pig targeted to diminish antibody binding and complement and coagulation cascade activation...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29359453/strong-xenoprotective-function-by-single-copy-transgenes-placed-sequentially-at-a-permissive-locus
#20
Beate Rieblinger, Konrad Fischer, Alexander Kind, Benedikt S Saller, Wiebke Baars, Marion Schuster, Lelia Wolf-van Buerck, Andrea Schäffler, Tatiana Flisikowska, Mayuko Kurome, Valeri Zakhartchenko, Barbara Kessler, Krzysztof Flisikowski, Eckhard Wolf, Jochen Seissler, Reinhard Schwinzer, Angelika Schnieke
BACKGROUND: Multiple xenoprotective transgenes are best grouped at a single locus to avoid segregation during breeding and simplify production of donor animals. METHODS: We used transgene stacking to place a human CD55 transgene adjacent to a human heme oxygenase 1 construct at the porcine ROSA26 locus. A transgenic pig was analyzed by PCR, RT-PCR, droplet digital PCR, immunohistochemistry, immunofluorescence, and flow cytometry. Resistance to complement-mediated cell lysis and caspase 3/7 activation were determined in vitro...
March 2018: Xenotransplantation
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