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Nizar I Mourad, Pierre Gianello
Encapsulated porcine islets could be used to treat type I diabetes without necessitating severe immunosuppression. Islet survival and secretory function in the encapsulation device need to be preserved to ensure efficient insulin output in response to surrounding stimuli. In the present study, we evaluated stimulated insulin secretion from adult and neonatal pig islets seeded on an acellular collagen matrix and encapsulated in alginate during long-term culture. Pig islets survived longer and secreted more insulin when cultured on acellular porcine dermis compared to human fascia...
September 19, 2018: Xenotransplantation
Heather E Levy, Christopher Burlak
No abstract text is available yet for this article.
September 17, 2018: Xenotransplantation
Jong-Min Kim, Jun-Seop Shin, Sungyoung Han, Byoung-Hoon Min, Won Young Jeong, Ga Eul Lee, Min Sun Kim, Seeun Kwon, Hyunwoo Chung, Hee Jung Kang, Chung-Gyu Park
Pig-to-nonhuman primate (NHP) islet transplantation has been widely conducted as a preclinical xenotransplantation model prior to human clinical trial. Portal vein thrombosis is one of the complications associated with islet infusion through the portal vein into the liver. Here, we briefly report severe case of ascites formation accompanied by portal vein thrombi after pig-to-NHP islet xenotransplantation in a rhesus monkey. Meticulous prophylactic treatment such as continuous heparin infusion should be implemented to prevent portal vein thrombi in pig-to-NHP islet transplantation models...
September 8, 2018: Xenotransplantation
Jinsoo Rhu, Kyo Won Lee, Kyeong Sik Kim, Ji Soo Lee, Sung Joo Kim, Jae Berm Park
We designed this study to define reference values of the cynomolgus monkey coagulation system, as the normal range of values has not been established. Measurement of coagulation function was determined by testing plasma samples from 30 healthy male cynomolgus monkeys. Prothrombin time (PT), PT activity, PT international normalized ratio (INR), activated prothrombin time (aPTT), antithrombin III activity, factor II, V, VII, VIII, IX, X, XI, and XII, protein C activity, protein S activity, and d-dimer were measured using standardized techniques...
September 5, 2018: Xenotransplantation
Lars Burdorf, Donald Harris, Siamak Dahi, Christopher Laird, Tianshu Zhang, Franchesca Ali, Aakash Shah, Mercedes Thompson, Gheorghe Braileanu, Xiangfei Cheng, Evelyn Sievert, Evan Schwartz, Selin Sendil, Dawn M Parsell, Emily Redding, Carol J Phelps, David L Ayares, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Elevated pulmonary vascular resistance (PVR), platelet adhesion, coagulation activation, and inflammation are prominent features of xenolung rejection. Here, we evaluate the role of thromboxane and histamine on PVR, and their contribution to other lung xenograft injury mechanisms. METHODS: GalTKO.hCD46 single pig lungs were perfused ex vivo with fresh heparinized human blood: lungs were either treated with 1-Benzylimidazole (1-BIA) combined with histamine receptor blocker famotidine (n = 4) or diphenhydramine (n = 6), 1-BIA alone (n = 6) or were left untreated (n = 9)...
September 3, 2018: Xenotransplantation
Mo Chen, Yuantao Wang, Hui Wang, Liguang Sun, Yaowen Fu, Yong-Guang Yang
CD47 is a ubiquitously expressed transmembrane glycoprotein that plays a complex role in regulation of cell survival and function. We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of cellular xenografts by macrophages. However, the role of CD47 in solid organ transplantation remains undetermined. Here, we explored this question in mouse models of heart allotransplantation. We observed that the lack of CD47 in donor hearts had no deleterious effect on graft survival in syngeneic or single MHC class I-mismatched recipients, in which both wild-type (WT) and CD47 knockout (CD47 KO) mouse hearts survived long term with no sign of rejection...
August 23, 2018: Xenotransplantation
David K C Cooper, Hidetaka Hara, Hayato Iwase, Charles Adam Banks, David C Cleveland
There is a continuing need for donor hearts for infants with complex congenital heart defects. The transplantation of hearts from neonatal pigs would be an alternative to human organs, particularly if donor-specific immunological tolerance could be achieved. The great majority of infant humans do not make natural (preformed) antibodies against triple-knockout (TKO) pigs (that do not express any of the three known pig antigens against which humans have natural anti-pig antibodies). The transplantation of a heart from a TKO pig into an infant would therefore minimize any risk of early antibody-mediated rejection, and, with adequate immunosuppressive therapy, prolonged graft survival may well be achieved...
August 20, 2018: Xenotransplantation
Susan A Safley, Norma S Kenyon, Dora M Berman, Graham F Barber, Melissa Willman, Stephanie Duncanson, Neal Iwakoshi, Robert Holdcraft, Lawrence Gazda, Peter Thompson, I Raul Badell, Athanassios Sambanis, Camillo Ricordi, Collin J Weber
BACKGROUND: Xenogeneic donors would provide an unlimited source of islets for the treatment of type 1 diabetes (T1D). The goal of this study was to assess the function of microencapsulated adult porcine islets (APIs) transplanted ip in streptozotocin (STZ)-diabetic non-human primates (NHPs) given targeted immunosuppression. METHODS: APIs were encapsulated in: (a) single barium-gelled alginate capsules or (b) double alginate capsules with an inner, islet-containing compartment and a durable, biocompatible outer alginate layer...
August 17, 2018: Xenotransplantation
Tae-Ki Lee, Jong-Min Kim, Seok Hwa Choi
BACKGROUND: A long-segmental tracheal lesion is difficult to repair by tracheal allotransplantation due to the lack of a well-defined blood supply for blood vessel anastomosis. The donor trachea needs to be revascularized within a well-vascularized soft tissue flap for several months to allow successful trachea allotransplantation. To date, xenotransplantation using the wild-type or genetically modified pig has been widely studied. The object of this study was to evaluate the feasibility of a small-sized (2 × 2 cm) wild-type pig tracheal patchy in a dog tracheal defect model before trying a long-segment tracheal defect model and using a genetically modified pig as a donor in dog xenotransplantation...
August 17, 2018: Xenotransplantation
Hyuk Jin Choi, Joon Young Hyon, Hyung Keun Lee, Jong-Suk Song, Tae-Young Chung, Hyojung Mo, Jaeyoung Kim, Jae-Eun Kim, Hyounggyoon Yoo, Seung Hwan Lee, Ivo Kwon, Mee Kum Kim
No abstract text is available yet for this article.
August 4, 2018: Xenotransplantation
Hyuk Jin Choi, Chang Ho Yoon, Joon Young Hyon, Hyung Keun Lee, Jong-Suk Song, Tae-Young Chung, Hyojung Mo, Jaeyoung Kim, Jae-Eun Kim, Bong-Jin Hahm, Jaeseok Yang, Wan Beom Park, Mee Kum Kim
BACKGROUND: Xenotransplantation using fresh porcine corneas has been suggested as a feasible alternative to overcome the shortage of human donor corneas. Successful long-term survival of grafts without evidence of xenozoonosis in clinically applicable pig-to-non-human primate corneal transplantation model has brought researchers close to human clinical trials. Accordingly, we aimed to prepare a clinical trial protocol to conduct the first corneal xenotransplantation. METHODS: We developed the clinical trial protocol based on international consensus statement on conditions for undertaking clinical trials of corneal xenotransplantation developed by the International Xenotransplantation Society...
July 31, 2018: Xenotransplantation
Konrad Fischer, Alexander Kind, Angelika Schnieke
This review gives a brief overview of the genetic modifications necessary for grafted porcine tissues and organs to overcome rejection in human recipients. It then focuses on the problem of generating and breeding herds of donor pigs carrying modified endogenous genes and multiple xenoprotective transgenes. A xenodonor pig optimised for human clinical use could well require the addition of ten or more xenoprotective transgenes. It is impractical to produce the required combination of transgene by cross-breeding animals bearing individual transgenes at unlinked genetic loci, because independent segregation means that huge numbers of pigs would be required to produce relatively few donor animals...
July 28, 2018: Xenotransplantation
Jung-Sik Kim, Youngmee Jung, Su Hee Kim, Jun-Seop Shin, Soo Hyun Kim, Chung-Gyu Park
BACKGROUND: Subcutaneous tissue is an attractive extra-hepatic heterotopic site for islet transplantation; however, poor oxygen tension and blood supply during early engraftment of implanted islets have limited the use of this site in clinical applications. METHODS: This study investigated the vascularization potential of hypoxia-preconditioned mesenchymal stem cells (3% O2 ; hypo-MSCs) in PLGA-based bio-artificial beds for subsequent subcutaneous islet transplantation...
July 28, 2018: Xenotransplantation
Robert W Holdcraft, Pradeep R Dumpala, Barry H Smith, Lawrence S Gazda
BACKGROUND: Allogeneic islet transplantation for the treatment of type 1 diabetes often requires multiple implant procedures, from as many as several human pancreas donors, to achieve lasting clinical benefit. Given the limited availability of human pancreases for islet isolation, porcine islets have long been considered a potential option for clinical use. Agarose-encapsulated porcine islets (macrobeads) permit long-term culture and thus a thorough evaluation of microbiological safety and daily insulin secretory capacity, prior to implantation...
July 28, 2018: Xenotransplantation
Kate E Smith, William G Purvis, Melissa A Davis, Catherine G Min, Amanda M Cooksey, Craig S Weber, Jana Jandova, Nicholas D Price, Diana S Molano, James Brett Stanton, Amy C Kelly, Leah V Steyn, Ronald M Lynch, Sean W Limesand, Michael Alexander, Jonathan R T Lakey, Karen Seeberger, Gregory S Korbutt, Kate R Mueller, Bernhard J Hering, Fiona M McCarthy, Klearchos K Papas
BACKGROUND: There is currently a shortage of human donor pancreata which limits the broad application of islet transplantation as a treatment for type 1 diabetes. Porcine islets have demonstrated potential as an alternative source, but a study evaluating islets from different donor ages under unified protocols has yet to be conducted. METHODS: Neonatal porcine islets (NPI; 1-3 days), juvenile porcine islets (JPI; 18-21 days), and adult porcine islets (API; 2+ years) were compared in vitro, including assessments of oxygen consumption rate, membrane integrity determined by FDA/PI staining, β-cell proliferation, dynamic glucose-stimulated insulin secretion, and RNA sequencing...
July 27, 2018: Xenotransplantation
Latifah Amin, Hasrizul Hashim, Zurina Mahadi, Anisah Che Ngah, Khaidzir Ismail
BACKGROUND: Advances in xenotransplantation have the potential to resolve the issue of organ shortages. Despite this, the procedure is expected to meet with a degree of resistance from the public. The purpose of this study was to identify the relevant factors influencing stakeholders' attitudes towards xenotransplantation. METHODS: A multidimensional survey instrument measuring attitudes to xenotransplantation, including the factors that predict such attitudes, was developed based on earlier studies and validated...
June 22, 2018: Xenotransplantation
Anu Paul, Vered Padler-Karavani
All living cells are covered with a dense "sugar-coat" of carbohydrate chains (glycans) conjugated to proteins and lipids. The cell surface glycome is determined by a non-template driven process related to the collection of enzymes that assemble glycans in a sequential manner. In mammals, many of these glycans are topped with sialic acids (Sia), a large family of acidic sugars. The "Sialome" is highly diverse owing to various Sia types, linkage to underlying glycans, range of carriers, and complex spatial organization...
June 22, 2018: Xenotransplantation
Wei Nie, Xiaoqian Ma, Cejun Yang, Zeyi Chen, Pengfei Rong, Minghua Wu, Jianhui Jiang, Mengqun Tan, Shounan Yi, Wei Wang
BACKGROUND: Hypoxia-induced damage is one of the key factors associated with islet graft dysfunction. Mesenchymal stem cells (MSCs) could be used to enhance the therapeutic effect of islet transplantation due to their paracrine potential such as exosomes. In this study, we investigated whether exosomes from human umbilical cord-derived MSC-conditioned medium (hu-MSC-CM) could increase the survival and function of neonatal porcine islet cell clusters (NICCs) exposed to hypoxia. METHODS: Neonatal porcine islet cell clusters were cultured with hu-MSC-CM, with or without exosomes, and native medium RPMI-1640 (Control) under hypoxic conditions (1% O2 )...
June 22, 2018: Xenotransplantation
Yang Liu, YingNan Zhang, Qingfeng Liang, Chao Yan, Li Wang, Jing Zhang, ZhiQiang Pan
BACKGROUND: In current non-human primate models, full-thickness porcine grafts could not achieve long-term survival without using potent systemic immunosuppressors. Moreover, the thickness disparity in xeno-PKP proved to be hard to manipulate and may cause several complications which also could prevent the grafts from long survival. Considering the advantages of Descemet's stripping automated endothelial keratoplasty (DSAEK) derived from its ultrathin graft and lower rejection rate, we hypothesize xeno-DSAEK may overcome these imperfections in xeno-PKP...
June 22, 2018: Xenotransplantation
Hanchao Gao, Qing Zhang, Jicheng Chen, David K C Cooper, Hidetaka Hara, Pengfei Chen, Ling Wei, Yanli Zhao, Jia Xu, Zesong Li, Zhiming Cai, Shaodong Luan, Lisha Mou
Whether porcine cytokines are induced after pig-to-primate xenotransplantation and activate human cells remains unknown. First, we investigated the regulation of porcine IL-6, IFN-γ, IL-1β, and TNF-α in xenotransplantation using an in vitro model in which porcine aortic endothelial cells (PAECs) and porcine peripheral blood mononuclear cells (PBMCs) were stimulated with human serum. Downstream cytokines/chemokines were monitored. Pro-inflammatory cytokines (IL-6, IFN-γ, and IL-1β) and chemokines (IL-8, MCP-1, and CXCL2) were upregulated in the both cell types...
June 22, 2018: Xenotransplantation
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