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 cellular anticoagulant defences and promote the development of thrombotic microangiopathy. Porcine endothelium may be particularly vulnerable because of cross-species molecular incompatibilities affecting the function of thrombomodulin and possibly TFPI. Recent data from small animal models suggest that transgenic overexpression of anti-thrombotic molecules on xenograft endothelium is capable of inhibiting intravascular thrombosis and preventing acute humoral rejection. In conjunction with existing genetic modifications (e.g. Gal KO, hDAF), this is a promising strategy to move xenotransplantation to the clinic.
journal_name
Xenotransplantationjournal_title
Xenotransplantationauthors
Cowan PJdoi
10.1111/j.1399-3089.2006.00368.xsubject
Has Abstractpub_date
2007-01-01 00:00:00pages
7-12issue
1eissn
0908-665Xissn
1399-3089pii
XEN368journal_volume
14pub_type
杂志文章,评审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: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: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:TNF and its receptors TNF-Receptor 1 (TNFR1, CD120a) and TNF-Receptor 2 (TNFR2, CD120b) have been implicated in the rejection of transplanted cells and organs. Although pig TNFR1 (pTNFR1) is known to mediate the effects of human TNF in a xenogeneic setting, it is unclear whether pig TNFR2 (pTNFR2) could cont...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2011.00634.x
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:The present study reports the development of a sensitive dot blot protocol for determining the level of preformed antibodies against porcine heart valve tissue derived from wild-type (WT) and α-Gal-KO (GGTA1-KO) pigs in human sera. METHODS:The assay uses decellularized and solubilized heart valve tissue; an...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12646
更新日期:2020-09-17 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::When clinical xenotransplantation is introduced, the costs associated with acquisition of a genetically engineered pig organ are as yet unknown. How will these costs compare with those currently associated with the acquisition of deceased human organs? An understanding of the financial aspects of deceased organ and ti...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12322
更新日期:2017-07-01 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::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
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: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: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:Blood group ABO-incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO-incompatible LD renal transplantation using specific anti-A/B antibody (Ab) immunoadsorption (IA) and anti-CD20 monoclonal Ab (mAb) treatment. PATI...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2006.00280.x
更新日期:2006-03-01 00:00:00
abstract::Xenotransplantion remains the most viable option for significant expansion of the donor organ pool in clinical transplantation. With the advent of nuclear transfer technologies, the production of transgenic swine has become a possibility. These animals have allowed transplant investigators to overcome humoral mechanis...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/j.1399-3089.2011.00687.x
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Porcine islet transplantation into diabetic non-human primates is considered most relevant in translational research supporting a clinical application. Most studies have focused on immunosuppressive protocols, while metabolic aspects have mainly been utilized in graft monitoring. We evaluated data from our g...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2011.00676.x
更新日期:2011-11-01 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::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::Type I diabetes remains a significant clinical problem in need of a reliable, generally applicable solution. Both whole organ pancreas and islet allotransplantation have been shown to grant patients insulin independence, but organ availability has restricted these procedures to an exceptionally small subset of the dia...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12095
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:The aim of the present study was to further investigate the characteristics of both graft-infiltrating cells and splenocytes during acute vascular rejection (AVR), cell-mediated rejection and non-rejection of vascularized concordant xenografts, by analysing both proinflammatory [interleukin-1beta (IL-1beta) ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2003.02032.x
更新日期:2003-07-01 00:00:00
abstract::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 internation...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12457
更新日期:2019-01-01 00:00:00
abstract::Islet transplantation is a potential treatment for diabetes mellitus and porcine pancreata may provide a readily available source of islets. The size, number and distribution of islets within the pancreas may influence the choice of age of donor for xenotransplantation. Samples (n = 3 per age group) from the dorsal an...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.1999.00009.x
更新日期:1999-05-01 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: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:AIM:To provide information on the specificity of induced anti-pig antibodies (Abs) in baboons after exposure and sensitization to pig antigens. MATERIALS AND METHODS:Baboons (n=7) received either porcine mobilized peripheral blood progenitor cells (n=3), kidney (n=3) or heart (n=1) transplants. After rejection of thes...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2003.01122.x
更新日期:2003-01-01 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::In addition to providing a large source of donor tissue, xenogeneic islet transplantation might avoid recurrent autoimmunity in patients with type 1 diabetes. To examine this possibility further, xenogeneic pig islets were transplanted into recipient mice in the presence or absence of autoimmunity. Spontaneously, non-...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2003.02040.x
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Activation of the clotting cascade is central in acute xenograft rejection (AHXR) that occurs when pig organs are transplanted into primates. The coagulopathy reported in this model is a very complex process that involves simultaneously coagulation factors, platelets and phospholipid-bearing cells (i.e., leu...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12024
更新日期:2013-03-01 00:00:00
abstract::For long-term xenograft survival, coagulation control is one of the remaining critical issues. Our attention has been directed toward human thrombomodulin (hTM), because it is expected to exhibit the following beneficial effects on coagulation control and cytoprotection: (i) to solve the problem of molecular incompati...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2012.00696.x
更新日期:2012-03-01 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: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