Abstract:
:We investigated the predictive biomarkers for graft rejection in pig-to-non-human primate (NHP) full-thickness corneal xenotransplantation (n = 34). The graft score (0-12) was calculated based on opacity, edema, and vascularization. Scores ≥ 6 were defined as rejection. NHPs were divided into two groups: (a) graft rejection within 6 months; and (b) graft survival until 6 months. In the evaluation of 2-week biomarkers, none of the NHPs showed rejection within 2 weeks and the 34 NHPs were divided into two groups: (a) entire rejection group (n = 16); and (b) survival group (n = 18). In the evaluation of 4-week biomarkers, four NHPs showing rejection within 4 weeks were excluded and the remaining 30 NHPs were divided into two groups: (a) late rejection group (n = 12); and (b) survival group (n = 18). Analysis of biomarker candidates included T/B-cell subsets, levels of anti-αGal IgG/M, donor-specific IgG/M from blood, and C3a from plasma and aqueous humor (AH). CD8+ IFNγ+ cells at week 2 and AH C3a at week 4 were significantly elevated in the rejection group. Receiver operating characteristic areas under the curve was highest for AH C3a (0.847) followed by CD8+ IFNγ+ cells (both the concentration and percentage: 0.715), indicating excellent or acceptable discrimination ability, which suggests that CD8+ IFNγ+ cells at week 2 and AH C3a at week 4 are reliable biomarkers for predicting rejection in pig-to-NHP corneal xenotransplantation.
journal_name
Xenotransplantationjournal_title
Xenotransplantationauthors
Yoon CH,Choi SH,Lee HJ,Kang HJ,Kim MKdoi
10.1111/xen.12515subject
Has Abstractpub_date
2019-07-01 00:00:00pages
e12515issue
4eissn
0908-665Xissn
1399-3089journal_volume
26pub_type
杂志文章abstract::The activation of the endothelial surface in xenografts is still a poorly understood process and the consequences are unpredictable. The role of Ca2+ -messaging during the activation of endothelial cells is well recognized and routinely measured by synthetic Ca2+ -sensitive fluorophors. However, these compounds requir...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12585
更新日期:2020-09-01 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:BACKGROUND: Various groups have reported prolonged diabetes reversal and graft function after porcine islet transplantation into diabetic macaques using different experimental designs (macaque source, islet source, type of immunosuppression): subsequently, the International Xenotransplantation Association has publishe...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12012
更新日期:2013-01-01 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::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::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:Autograft (AG) is the gold standard bone graft due to biocompatibility, osteoconductivity, osteogenicity, and osteoinductivity. Alternatives include allografts and xenografts (XG). METHODS:We investigated the osseointegration and biocompatibility of a decellularized porcine XG within a critical defect anima...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12662
更新日期:2020-11-26 00:00:00
abstract::The infusion of large numbers of porcine cells into primates in order to induce specific immunologic tolerance by mixed hematopoietic chimerism, results in thrombotic microangiopathy that can be fatal. For this reason, it is important to study in vitro the interaction of primate endothelial cells with pig cells. We sh...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2002.01066.x
更新日期:2002-05-01 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::Previous data suggest that natural anti-Galalpha1,3Gal (Gal) antibody (Ab) is produced by mature plasma cells. As thalidomide is effectively used in the treatment of patients with multiple myeloma, its effect on natural anti-Gal Ab production has been assessed in two baboons. During a 10-week course of thalidomide adm...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2003.00064.x
更新日期:2003-09-01 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::Mouse CD4+ T cells efficiently develop in fetal pig thymus (FP THY) grafts and repopulate the periphery of T cell and NK cell-depleted, thymectomized (ATX) mice. However, efficient peripheral repopulation of mouse CD8+ T cells does not occur in these mice. We have therefore evaluated the maturation and function of mou...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.1998.tb00015.x
更新日期:1998-02-01 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:As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient's native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12213
更新日期:2015-11-01 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: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::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::Cultures of hDAF transgenic porcine aortic endothelial cells (TPAEs) with levels of cell surface hDAF expression between 2000 and 300 000 molecules per cell have been used to determine the relationship between expression of hDAF and protection from human complement deposition in an in vitro model. At concentrations be...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2001.00086.x
更新日期:2001-05-01 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: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:Young people, and students in particular, generally have a positive attitude to xenotransplantation. We reported previously that university students attending their first year approved of the idea of transplanting animal organs into humans. The aim of this study was to evaluate the impact of a 3-yr course at...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2006.00307.x
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:The long-term viability and function of transplanted encapsulated neonatal porcine islets was examined in a diabetic patient. METHODS AND RESULTS:A 41-yr-old Caucasian male with type 1 diabetes for 18 yr was given an intraperitoneal transplant of alginate-encapsulated porcine islets at the dose of 15,000 is...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2007.00384.x
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND AND AIMS:Cell-based therapies for liver disease such as bioartificial liver rely on a large quantity and high quality of hepatocytes. Cold storage was previously shown to be a better way to preserve the viability and functionality of hepatocytes during transportation rather than freezing, but this was only p...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12512
更新日期:2019-07-01 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: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::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:Human cytomegalovirus (HCMV) infection or reactivation has been linked to allograft rejection resulting from endothelial injury and immune activation. In pig-to-human xenotransplantation, currently investigated to circumvent the shortage of human organs in transplantation medicine, the porcine endothelium wi...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2010.00594.x
更新日期:2010-07-01 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::The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosup...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12479
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Pancreatic islets are composed of different hormone-secreting cell types. A finely balanced combination of endocrine cells in the islets regulates intraportal vein secretions and plasma nutrient levels. Every islet cell type is distinguished by its specific secretory granule pattern and hormone content, endo...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12220
更新日期:2016-03-01 00:00:00