Abstract:
BACKGROUND:Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strategy to prevent accelerated coagulation in xenografts, we investigated the mechanism by which porcine endothelial cells (PECs) become procoagulant after contact with human blood. METHODS:The changes in TF mRNA levels and activity in PECs after incubation with 20% human serum or human bioactive molecules, including C5a, tumor necrosis factor-α (TNFα) and interleukin (IL)-1α, were evaluated using real-time PCR and the factor Xa chromogenic assay, respectively. The procoagulant changes in PECs by these agonists were evaluated by measuring the coagulation time of human citrated plasma suspended with PECs pretreated with each agonist. TF expression and coagulation times were also assessed in PECs transfected with short interfering RNA (siRNA) designed to knock down porcine TF. We also examined the production of proinflammatory cytokines in human whole-blood or plasma after contact with PECs, which were screened using the cytometric bead array system. TNFα levels were measured using ELISA in whole-blood after contact with PECs, with or without the addition of xenoreactive antibodies or C1 esterase inhibitor. RESULTS:Porcine TF mRNA and activity in PECs were up-regulated in response to human TNFα and IL-1α but were not affected by C5a or 20% human serum. Up-regulation of TF expression by human TNFα or IL-1α shortened PEC-induced coagulation time, while siRNA-mediated knockdown of TF expression prolonged coagulation time. The incubation of PECs with human whole-blood led to a significant increase in human TNFα levels in the blood, which was promoted by the addition of xenoreactive antibodies and prevented by C1 esterase inhibitor. CONCLUSIONS:Human TNFα level increases in human blood after contact with PECs, which is attributed to xenoreactive antibody binding and subsequent complement activation. Human TNFα induces procoagulant changes in PECs with increased TF expression. This study suggests that human TNFα may be one of the mediators linking complement activation with procoagulant changes in the xenoendothelium.
journal_name
Xenotransplantationjournal_title
Xenotransplantationauthors
Lee KG,Lee H,Ha JM,Lee YK,Kang HJ,Park CG,Kim SJdoi
10.1111/j.1399-3089.2012.00704.xsubject
Has Abstractpub_date
2012-05-01 00:00:00pages
186-95issue
3eissn
0908-665Xissn
1399-3089journal_volume
19pub_type
杂志文章abstract::The present historical review reports the clinical experiences of transplantations from animal to human. The first transplantation attempts were made without any knowledge of the species barrier. The pioneers of xenotransplantation realized xenotransfusions as early as the 16th century, then cell and tissue xenotransp...
journal_title:Xenotransplantation
pub_type: 历史文章,杂志文章
doi:10.1111/j.1399-3089.2004.00199.x
更新日期:2005-03-01 00:00:00
abstract::Islets isolated from multiple pancreas donors are often necessary to achieve euglycemia in type 1 diabetic patients treated by islet allotransplantation. This increases the burden on the limited pool of donor organs. After infusion into the portal vein, a substantial percentage of islets are lost in the immediate post...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/j.1399-3089.2007.00419.x
更新日期:2007-07-01 00:00:00
abstract::Liver xenografts transplanted from guinea pig to rat suffer from inadequate organ reperfusion and initial dysfunction, despite sufficient complement depletion using cobra venom factor (CVF). Reperfusion injury is prevented when complement depleted donors are treated with the prostacyclin analog epoprostenol. Histologi...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2001.00074.x
更新日期:2001-02-01 00:00:00
abstract:BACKGROUND:Extensive studies in rodents have identified olfactory ensheathing cells (OECs) as promising candidates for cell-based therapies of spinal cord and peripheral nerve injury. Previously, we demonstrated that short-term cultured adult porcine OECs can remyelinate the rodent and non-human primate spinal cord. He...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2009.00562.x
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:In vivo pig liver xenotransplantation preclinical trials appear to have poor efficiency compared to heart or kidney xenotransplantation because of xenogeneic rejection, including coagulopathy, and particularly thrombocytopenia. In contrast, ex vivo pig liver (wild type) perfusion systems have been proven to ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12550
更新日期:2020-01-01 00:00:00
abstract::Allogeneic hematopoietic stem cell transplantation (HSCT) and xenotransplantation are accompanied by viral reactivations and virus-associated complications resulting from immune deficiency. Here, in a Mauritian cynomolgus macaque model of fully MHC-matched allogeneic HSCT, we report reactivations of cynomolgus polyoma...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12578
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:The pig pancreas is considered to be the most suitable source of islets for xenotransplantation in patients with type I diabetes. The objective of this study was to assess the antigenicity of neonatal porcine islet-like cell clusters (NPCC), including the Galalpha1-3Galbeta1-4GlcNAc-R (alpha-Gal) and Hanganu...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2006.00335.x
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Little information is available regarding the precise swine leukocyte antigen (SLA)-derived immunogenic peptides that are presented in the context of human HLA molecules. Here, we identified SLA-derived immunogenic peptides that are presented in association with human HLA-A2 molecule. METHODS:The SLA-derive...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12119
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:In pig-to-human xenotransplantation, interactions between human natural killer (NK) cells and porcine endothelial cells (pEC) are characterized by recruitment and cytotoxicity. Protection from xenogeneic NK cytotoxicity can be achieved in vitro by the expression of the non-classical human leukocyte antigen-E...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12357
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Xenotransplantation using pig cells, tissues, or organs may be associated with the transmission of porcine microorganisms and the development of zoonoses. Among all porcine microorganisms porcine endogenous retroviruses (PERVs) represent a special risk because they are integrated in the genome of all pigs an...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12102
更新日期:2014-07-01 00:00:00
abstract::Fetal pig islets, xenografted after organ culture into non-immunosuppressed prediabetic NOD mice, are rejected within 10 days. Immunosuppression with anti-T cell (anti-CD4 and anti-CD3) monoclonal antibodies alone is highly effective in delaying graft rejection in this discordant model, but rejection eventually occurs...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.1998.tb00030.x
更新日期:1998-08-01 00:00:00
abstract::Xenotransplantation has the potential to alleviate the organ shortage that prevents many patients with end-stage renal disease from enjoying the benefits of kidney transplantation. Despite significant advances in other models, pig-to-primate kidney xenotransplantation has met limited success. Preformed anti-pig antibo...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12166
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND:Manipulating the pig genome to increase compatibility with human biology may facilitate the clinical application of xenotransplantation. Genetic modifications to pig cells have been made by sequential recombination in fetal fibroblasts and liver-derived cells followed by cross-breeding or somatic cell nuclea...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12131
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Whilst macrohemodynamic function of porcine xenografts transplanted into baboons has been assessed perioperatively, the ability of the xenograft to maintain systemic microcirculatory perfusion has not been investigated after pig-to-baboon xenotransplantation so far. METHODS:We investigated the sublingual mi...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2011.00645.x
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:Both the complement and the coagulation systems play important roles in the development of hyperacute or acute antibody-mediated xenograft rejection. Atrase B is a novel metalloproteinase isolated from the venom of Naja atra. In this study, we investigated the inhibitory effects of atrase B on complement act...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12616
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:In the α1,3-galactosyltransferase knockout (α-GalT KO) pig era, identification of the non-Gal epitopes is necessary for successful pig-to-human xenotransplantation. Recently, we successfully detected α-Gal epitopes as well as Hanganutziu-Deicher (H-D) antigens from the N-glycans in the pig heart tissues, whi...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12045
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Xenotransplantation of porcine islets has emerged in recent decades as a potential treatment for type 1 diabetes (T1D). Current methods of detection, indicative of successful engraftment, occur downstream of actual islet death. Epigenetic biomarkers can be detected in circulating cell-free DNA (cfDNA) to pro...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12570
更新日期:2020-03-01 00:00:00
abstract::Patients in whom type 1 diabetes is complicated by impaired awareness of hypoglycemia and recurrent episodes of severe hypoglycemia are candidates for islet or pancreas transplantation if severe hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run-in per...
journal_title:Xenotransplantation
pub_type: 共识发展会议,杂志文章
doi:10.1111/xen.12228
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Swine infectious pathogens, especially viruses, represent a potential public health risk associated with the use of pig tissues for xenotransplantation in humans. We hypothesized that porcine circovirus type I (PCV-1) may infect human mononuclear cells, resulting in ultrastructural alterations of the target ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2005.00249.x
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:Recently, we have shown that an immunosuppression regimen including costimulation blockade via anti-CD154 antibody significantly prolongs the cardiac xenograft survival in a GTKO.hCD46Tg pig-to-baboon heterotopic xenotransplantation model. Unfortunately, many coagulation disorders were observed with the use ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12066
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Microvascular thrombosis is a prominent characteristic of delayed xenograft rejection, therefore the effects of antiplatelet therapy with aspirin and clopidogrel on long-term cardiac xenograft function was investigated in a heterotopic pig-to-baboon cardiac transplant model. METHODS:Donor hearts from human ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2004.00159.x
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:Ubiquitous expression of T-cell regulatory transgenes such as the cytotoxic T lymphocyte-associated antigen 4 (CTLA4) or the high-affinity variant LEA29Y improves xeno graft survival. Such donor pigs are however immunocompromised and susceptible to infection. Continous high expression of CTLA4 or LEA29Y in t...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12634
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Dysregulation of coagulation is considered a major barrier against successful pig organ xenotransplantation in non-human primates. Inflammation is known to promote activation of coagulation. The role of pro-inflammatory factors as well as the relationship between inflammation and activation of coagulation in...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12133
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Porcine islet transplantation is emerging as an attractive option for the treatment of patients with type 1 diabetes, with the possibility of providing islets of higher and more consistent quality and in larger volumes than available from human pancreata. The use of encapsulated neonatal porcine islets (ENPI...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12005
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Making xenotransplantation socially acceptable is the first step in working toward the promotion of this potential therapy option for providing transplant organs. OBJECTIVE:To analyze the attitude toward xenotransplantation among the Latin American population resident in Florida (the USA), and to determine ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12250
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12087
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Despite overcoming xenograft hyperacute rejection (HAR), Gal (galactose-alpha1,3-galactose) expression may not be completely eliminated from the alpha1,3-galactosyltransferase gene knockout (Gal KO) pig because of alternative galactosyltransferases. Whether low levels of "residual" Gal are still susceptible ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2007.00437.x
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Liver fibrosis results from accumulation of extracellular matrix components and is associated with many chronic hepatic diseases. There is to date no specific therapy for this disease, and patients receive treatment for its associated complications. Specific progenitor cells, known as oval cells, are present...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2006.00344.x
更新日期:2006-11-01 00:00:00
abstract::The effects of pre-transplant blood transfusion vary from induction of antibodies and accelerated graft rejection, to prolonged survival and even tolerance. The beneficial 'transfusion effect' in allotransplantation is believed to be merely T-cell mediated. In xenotransplantation, T-cell independent mechanisms form a ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2001.00102.x
更新日期:2001-11-01 00:00:00
abstract::The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical tria...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/j.1399-3089.2010.00592.x
更新日期:2010-09-01 00:00:00