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 be effective in "bridging" liver failure patients until subsequent liver allotransplantation, and transgenic (human CD55/CD59) modifications have even prolonged the duration of pig liver perfusion. Despite the fact that hepatocyte cell lines have also been proposed for extracorporeal blood circulation in conditions of acute liver failure, porcine hepatocyte cell lines, and the GalT-KO background in particular, have not been developed and applied in this field. Herein, we established immortalized wild-type and GalT-KO porcine hepatocyte cell lines, which can be used for artificial liver support systems, cell transplantation, and even in vitro studies of xenotransplantation. METHODS:Primary hepatocytes extracted from GalT-KO and wild-type pigs were transfected with SV40 LT lentivirus to establish immortalized GalT-KO porcine hepatocytes (GalT-KO-hep) and wild-type porcine hepatocytes (WT). Hepatocyte biomarkers and function-related genes were assessed by immunofluorescence, periodic acid-Schiff staining, indocyanine green (ICG) uptake, biochemical analysis, ELISA, and RT-PCR. Furthermore, the tumorigenicity of immortalized cells was detected. In addition, a complement-dependent cytotoxicity (CDC) assay was performed with GalT-KO-hep and WT cells. Cell death and viability rates were assessed by flow cytometry and CCK-8 assay. RESULTS:GalT-KO and wild-type porcine hepatocytes were successfully immortalized and maintained the characteristics of primary porcine hepatocytes, including albumin secretion, ICG uptake, urea and glycogen production, and expression of hepatocyte marker proteins and specific metabolic enzymes. GalT-KO-hep and WT cells were confirmed as having no tumorigenicity. In addition, GalT-KO-hep cells showed less apoptosis and more viability than WT cells when exposed to complement and xenogeneic serum. CONCLUSIONS:Two types of immortalized cell lines of porcine hepatocytes with GalT-KO and wild-type backgrounds were successfully established. GalT-KO-hep cells exhibited higher viability and injury resistance against a xenogeneic immune response.
journal_name
Xenotransplantationjournal_title
Xenotransplantationauthors
Wang Q,Zhang X,Wang B,Bai G,Pan D,Yang P,Tao K,Li X,Dou Kdoi
10.1111/xen.12550subject
Has Abstractpub_date
2020-01-01 00:00:00pages
e12550issue
1eissn
0908-665Xissn
1399-3089journal_volume
27pub_type
杂志文章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: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: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::Post-transplantation infections are common in allograft recipients and should be expected in all immunocompromised hosts. Based on the need for immunosuppression in xenotransplantation, procedures developed to enhance safety in allotransplantation can be applied in future xenotransplantation clinical trials. Standardi...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12423
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:The JAK/STAT (Janus Tyrosine Kinase, Signal Transducers and Activators of Transcription) pathway is associated with cytokine or growth factor receptors and it is critical for growth control, developmental regulation and homeostasis. The use of porcine ocular cells as putative xenotransplants appears theoreti...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12070
更新日期:2013-11-01 00:00:00
abstract::We describe in this report the production and characterization of monoclonal antibodies (mAb) to the swine homologues of CD11a and CD18 antigens, and their use for phenotypic and functional analysis of porcine leukocytes. Monoclonal antibodies BL1H8 and BL2F1 precipitated two bands of approximately 170 and 95 kDa, whe...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1034/j.1399-3089.2000.00574.x
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Descemet's membrane endothelial keratoplasty (DMEK) might be a promising technique for future xeno-corneal transplantation due to its ultrathin graft, extremely low rejection occurrence, suture-free graft fixation, and minimal immunosuppressive regime usage. The aim of this study is to explore the feasibilit...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12407
更新日期:2018-09-01 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: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:Islet transplantation is potentially a promising therapy for the restoration of carbohydrate control to diabetic patients. However, the global application of islet transplantation requires a ubiquitous source of beta cells. The xenotransplantation of porcine islets would provide such a source. Success in por...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2009.00548.x
更新日期:2009-11-01 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::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::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: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: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:The Westran pig has been purposely inbred for use in xenotransplantation. The herd originated in the wild from a limited gene pool and has been inbred by repeated full-sib matings for nine generations. METHODS:The aim of this study was to evaluate the level of inbreeding by functional assays, such as bi-dir...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2005.00230.x
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:We have successfully performed heart transplantation despite the most unfavourable risk factors for graft and patient survival: the presence of a high level of antibodies (Abs) against the donor's human leukocyte antigens (HLA) class I/II and blood group A1 antigens. The present study concerns post-transplan...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/j.1399-3089.2006.00276.x
更新日期:2006-03-01 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:The programmed cell death-1 (PD-1, CD279)/PD-Ligand1 (PD-L1, CD274) receptor system is crucial for controlling the balance between immune activation and induction of tolerance via generation of inhibitory signals. Expression of PD-L1 is associated with reduced immunogenicity and renders cells and tissues to ...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12387
更新日期:2018-09-01 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: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 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::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 rej...
journal_title:Xenotransplantation
pub_type: 杂志文章
doi:10.1111/xen.12515
更新日期:2019-07-01 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: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::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::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::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::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:Over time, the notion of public has evolved. While the concept of public was initially conceived of as a single undifferentiated entity, the common understanding is now that a variety of differentiated, multifaceted and multiple public(s) can be constructed for different purposes. This is equally true in xen...
journal_title:Xenotransplantation
pub_type: 杂志文章,评审
doi:10.1111/xen.12120
更新日期:2014-11-01 00:00:00