Abstract:
:Highly sensitized patients awaiting kidney transplantation may be potential candidates for future clinical trials using pig organ donors. Because of crossreactivity between human leucocyte antigens (HLA) and swine leucocyte antigens (SLA), such patients might have heightened T-cell responses to porcine xenoantigens. We determined whether lymphocytes from allo-sensitized patients displayed secondary (cyclosporine resistant) T-cell proliferative responses against porcine xenoantigens. Lymphocytes from six non-sensitized, seven sensitized [immunoglobulin G (IgG) panel reactive antibodies (PRA) 11 to 84%], 14 highly sensitized patients (IgG PRA > 84%) and 12 healthy individuals were tested [in the presence and absence of Cyclosporin A (CsA)] to determine their proliferative response to human (allogeneic) and to porcine (xenogeneic) stimulator cells. Lymphocytes from all study groups showed a strong proliferative response to allogeneic and xenogeneic stimulator cells with no significant difference between non-sensitized and sensitized individuals. Addition of CsA (100 and 500 ng/ml) inhibited (>90%) proliferation of lymphocytes from all non-sensitized patients to both allogeneic and xenogeneic stimulators. CsA was less effective at inhibiting proliferation of lymphocytes from sensitized patients and highly sensitized patients to allogeneic stimulators [29% (n=21) and 50% (n=42) respectively were resistant to CsA inhibition (100 ng/ml)]. In contrast, cyclosporine inhibited proliferation of lymphocytes from the majority of sensitized and highly sensitized patients to xenogeneic stimulator cells [14% (n=21) and 14% (n=42) respectively were resistant to CsA inhibition (100 ng/ml)]. HLA sensitized patients awaiting renal transplantation display cyclosporine resistant proliferative T-cell responses to allogeneic stimulators but proliferative responses to xenogeneic stimulators are more amenable to suppression by CsA. This finding suggests that humoral sensitisation to HLA antigens is not necessarily indicative of a heightened in vitro T-cell response to SLA antigens.
journal_name
Xenotransplantationjournal_title
Xenotransplantationauthors
Oostingh GJ,Davies HF,Bradley JA,Taylor CJdoi
10.1034/j.1399-3089.2003.00089.xsubject
Has Abstractpub_date
2003-11-01 00:00:00pages
545-51issue
6eissn
0908-665Xissn
1399-3089journal_volume
10pub_type
杂志文章abstract::Complement plays a major role in hyperacute rejection of xenografts. In order to overcome this, we are developing, by minimal mutagenesis, a modified C3 molecule that, like cobra venom factor (CVF), escapes normal complement regulatory processes and inhibits complement-mediated responses by systemic depletion of C3. U...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.1998.tb00005.x
更新日期:1998-02-01 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::Acute humoral rejection remains the major barrier to long-term pig-to-primate xenograft survival, and microvascular thrombosis is a critical element of the rejection process. It appears that persistent endothelial cell activation and injury, by even low levels of anti-graft antibodies, eventually overwhelm the cellula...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/j.1399-3089.2006.00368.x
更新日期:2007-01-01 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:In pig-to-nonhuman primate solid organ xenotransplantation using organs from donors transgenic for human decay-accelerating factor (hDAF), the main type of rejection is antibody-mediated (acute humoral xenograft rejection, AHXR). This occurs despite the complement-regulatory function of the transgene, neutra...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2004.00184.x
更新日期:2005-01-01 00:00:00
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:AIM:to study whether sensitization to pig antigens results in humoral and/or cellular sensitization to alloantigens in baboons, and thus increases the risks of organ allotransplantation after xenotransplantation. Serum from baboons that were naive (n = 4), sensitized to Gal alpha 1,3Gal (Gal) antigens (n = 2), or sensi...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2004.00075.x
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:In vivo xenotransplantation modeling in large animal species is often performed in nonhuman primates, including baboons. For proper data interpretation, reference values for clinical chemistry and hematology are required. METHODS:These values are available from baseline levels in animals subjected to tolera...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2004.00171.x
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Xenotransplantation of porcine islets can reverse diabetes in non-human primates. The remaining hurdles for clinical application include safe and effective T-cell-directed immunosuppression, but protection against the innate immune system and coagulation dysfunction may be more difficult to achieve. Islet-ta...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12145
更新日期:2015-01-01 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::My purpose in these remarks is to stimulate us to consider the vast array that nature has provided us in the differentiation of species, and to examine the possibility that some of these differences might prove useful in other species, including man. ...
journal_title:Xenotransplantation
pub_type:
doi:10.1034/j.1399-3089.2000.00045.x
更新日期:2000-05-01 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::Development of coagulation disorders remains a major challenge in pig-to-primate organ xenotransplantation. Our previous studies demonstrated that porcine aortic endothelial cells (pAEC) activate human platelets to express tissue factor (TF). In this study, we investigated the molecular interaction between human plate...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12068
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:The induced antibodies against Galalpha1,3Gal (Gal) and non-Gal epitopes may contribute to delayed xenograft rejection (DXR). We asked whether blockade of the CD40/CD154 and CD28/B7 co-stimulatory pathways modulates the baboon elicited antibody response to pig Gal and non-Gal antigens. METHODS:Eighteen babo...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2005.00221.x
更新日期:2005-05-01 00:00:00
abstract::Orthotopic liver transplantation (OLT) is the only definitive treatment option for many patients with end-stage liver disease. Current supply of donor livers for OLT is not keeping up with the growing demand. To overcome this problem, a number of experimental strategies have been developed either to provide a bridge t...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12668
更新日期:2020-12-08 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::Decellularized bovine pericardium (DBP)-based biomeshes are the gold standard in reconstructive surgery. In order to prolong their stability after the transplantation, various chemical cross-linking strategies are employed. However, structural and functional properties of the biomeshes differ in dependence on the cros...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12506
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:The continued presence of a primate antibody-mediated response to cells and organs from alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs indicates that there may be antigens other than Gal alpha 1,3Gal (alpha Gal) against which primates have xenoreactive antibodies. Human and baboon sera were tested ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2010.00579.x
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND:Safe and reliable diabetes models are a key prerequisite for advanced preclinical studies on diabetes. Chemical induction is the standard model of diabetes in rodents and also widely used in large animal models of non-human primates and minipigs. However, uncertain efficacy, the potential of beta-cell regene...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12255
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND:Endothelial damage is a critical step in the development of (xeno) transplantation-related and cardiovascular pathology. In humans, the amount of circulating endothelial cells (CEC) correlates to disease intensity and functions as a valuable damage marker. While (xeno) transplantation and cardiovascular rese...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12018
更新日期:2013-01-01 00:00:00
abstract: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-huma...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12400
更新日期:2018-05-01 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::The first blood transfusions in humans were xenotransfusions, carried out by Jean-Baptiste Denis beginning in 1667. Richard Lower, Matthäus Purmann and Georges Mercklin also experimented with the use of animal blood for transfusion until this practice was forbidden in 1670, after the death of one of Denis's patients. ...
journal_title:Xenotransplantation
pub_type: 历史文章,杂志文章
doi:10.1111/j.1399-3089.2007.00404.x
更新日期:2007-05-01 00:00:00
abstract::The last 15 years or so have seen exciting progress in xenotransplantation, with porcine organ grafts surviving months or even years in non-human primates. These advances reflect the application of new scientific knowledge, improved immunosuppressive agents, and genetic engineering. The field has recently enjoyed a re...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12419
更新日期:2018-05-01 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::Type 1 diabetes can be cured by transplantation of isolated pancreatic islets. Because of the shortage of human donor tissue, adult porcine islets (APIs) constitute a possible alternative tissue source. Upon intraportal injection, islets are subjected to an instant blood-mediated inflammatory reaction (IBMIR) leading ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1046/j.1399-3089.2003.00104.x
更新日期:2004-03-01 00:00:00
abstract:UNLABELLED:Xenotransplantation using porcine organs may resolve a chronic shortage of donor organs for clinical transplantation if significant immunological barriers can be overcome. To determine the potential role of T lymphocytes in Xenograft (Xg) rejection, we transplanted transgenic hCD46 porcine hearts heterotopic...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2005.00258.x
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Innovations in transgenic technology have facilitated improved xenograft survival. Additional gene expression appears to be necessary to overcome the remaining immune and biologic incompatibilities. We report for the first time the novel use of six-gene modifications within a pig-to-baboon cardiac xenotransp...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12330
更新日期:2017-11-01 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: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