Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications.

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 polyomavirus, lymphocryptovirus, and cytomegalovirus, macaque viruses analogous to HSCT-associated human counterparts BK virus, Epstein-Barr virus, and human cytomegalovirus. Viral replication in recipient macaques resulted in characteristic disease manifestations observed in HSCT patients, such as polyomavirus-associated hemorrhagic cystitis and tubulointerstitial nephritis or lymphocryptovirus-associated post-transplant lymphoproliferative disorder. However, in most cases, the reconstituted immune system, alone or in combination with short-term pharmacological intervention, exerted control over viral replication, suggesting engraftment of functional donor-derived immunity. Indeed, the donor-derived reconstituted immune systems of two long-term engrafted HSCT recipient macaques responded to live attenuated yellow fever 17D vaccine (YFV 17D) indistinguishably from untransplanted controls, mounting 17D-targeted neutralizing antibody responses and clearing YFV 17D within 14 days. Together, these data demonstrate that this macaque model of allogeneic HSCT recapitulates clinical situations of opportunistic viral infections in transplant patients and provides a pre-clinical model to test novel prophylactic and therapeutic modalities.

journal_name

Xenotransplantation

journal_title

Xenotransplantation

authors

Wu HL,Weber WC,Shriver-Munsch C,Swanson T,Northrup M,Price H,Armantrout K,Robertson-LeVay M,Reed JS,Bateman KB,Mahyari E,Thomas A,Junell SL,Hobbs TR,Martin LD,MacAllister R,Bimber BN,Slifka MK,Legasse AW,Moats C,A

doi

10.1111/xen.12578

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

e12578

issue

4

eissn

0908-665X

issn

1399-3089

journal_volume

27

pub_type

杂志文章
  • Pigs expressing the human inhibitory ligand PD-L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties.

    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

    authors: Buermann A,Petkov S,Petersen B,Hein R,Lucas-Hahn A,Baars W,Brinkmann A,Niemann H,Schwinzer R

    更新日期:2018-09-01 00:00:00

  • History of xenotransplantation.

    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

    authors: Deschamps JY,Roux FA,Saï P,Gouin E

    更新日期:2005-03-01 00:00:00

  • An overview of the role of society and risk in xenotransplantation.

    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

    authors: Sobbrio P,Jorqui M

    更新日期:2014-11-01 00:00:00

  • Tacrolimus inhibits discordant islet xenograft rejection: a study in the pig-to-rat model.

    abstract::The aim of the present study was to evaluate the immunosuppressive effect of tacrolimus (TAC) in discordant islet xenotransplantation. Fetal porcine islet-like cell clusters (ICCs) were transplanted under the kidney capsule in normoglycemic rats treated with TAC monotherapy, TAC plus other immunosuppressive drugs or c...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2003.00068.x

    authors: Song Z,Zhang J,Bennet W,Wennberg L

    更新日期:2003-11-01 00:00:00

  • Anti-Gal antibody-mediated skin graft rejection requires a threshold level of Gal expression.

    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

    authors: Murray-Segal L,Gock H,Cowan PJ,d'Apice AJ

    更新日期:2008-02-01 00:00:00

  • Release of pig leukocytes and reduced human NK cell recruitment during ex vivo perfusion of HLA-E/human CD46 double-transgenic pig limbs with human blood.

    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

    authors: Puga Yung G,Bongoni AK,Pradier A,Madelon N,Papaserafeim M,Sfriso R,Ayares DL,Wolf E,Klymiuk N,Bähr A,Constantinescu MA,Voegelin E,Kiermeir D,Jenni H,Rieben R,Seebach JD

    更新日期:2018-01-01 00:00:00

  • Ultrastructural alterations in human blood leukocytes induced by porcine circovirus type 1 infection.

    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

    authors: Arteaga-Troncoso G,Guerra-Infante F,Rosales-Montaño LM,Díaz-García FJ,Flores-Medina S

    更新日期:2005-11-01 00:00:00

  • Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival.

    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

    authors: Schirmer JM,Fass DN,Byrne GW,Tazelaar HD,Logan JS,McGregor CG

    更新日期:2004-09-01 00:00:00

  • Effect of cell surface concentration of human DAF on transgenic pig aortic endothelial cells on the degree of protection afforded against human complement deposition.

    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

    authors: Carrington CA,dos Santos Cruz G

    更新日期:2001-05-01 00:00:00

  • Generating liver using blastocyst complementation: Opportunities and challenges.

    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

    authors: Aravalli RN

    更新日期:2020-12-08 00:00:00

  • Initial experience with the human anti-human CD154 monoclonal antibody, ABI793, in pig-to-baboon xenotransplantation.

    abstract:BACKGROUND:ABI793 (ABI) is a human monoclonal antibody (mAb) specific for human CD154. To assess the suitability of ABI for baboon transplantation studies, we carried out in vitro studies to determine ABI's reactivity with baboon cells expressing CD154, performed in vivo pharmacokinetic studies in two baboons, and test...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2004.00148.x

    authors: Knosalla C,Ryan DJ,Moran K,Gollackner B,Schuler W,Sachs DH,Awwad M,Schuurman HJ,Cooper DK

    更新日期:2004-07-01 00:00:00

  • First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--Chapter 6: patient selection for pilot clinical trials of islet xenotransplan

    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

    authors: Hering BJ,O'Connell PJ

    更新日期:2016-01-01 00:00:00

  • Encouraging experience using multi-transgenic xenografts in a pig-to-baboon cardiac xenotransplantation model.

    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

    authors: Chan JL,Singh AK,Corcoran PC,Thomas ML,Lewis BG,Ayares DL,Vaught T,Horvath KA,Mohiuddin MM

    更新日期:2017-11-01 00:00:00

  • Reference values for clinical chemistry and clinical hematology parameters in baboons.

    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

    authors: Schuurman HJ,Smith HT,Cozzi E

    更新日期:2004-11-01 00:00:00

  • Xenotransfusions, past and present.

    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

    authors: Roux FA,Saï P,Deschamps JY

    更新日期:2007-05-01 00:00:00

  • Bone xenotransplantation: A review of the history, orthopedic clinical literature, and a single-center case series.

    abstract:BACKGROUND:One-half of all orthopedic surgeries require bone grafting for successful outcomes in fusions, reconstructive procedures, and the treatment of osseous defects resulting from trauma, tumor, infection, or congenital deformity. Autologous bone grafts are taken from the patient's own body and remain the "gold st...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12600

    authors: Bracey DN,Cignetti NE,Jinnah AH,Stone AV,Gyr BM,Whitlock PW,Scott AT

    更新日期:2020-09-01 00:00:00

  • Production of cloned pigs expressing human thrombomodulin in endothelial cells.

    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

    authors: Yazaki S,Iwamoto M,Onishi A,Miwa Y,Hashimoto M,Oishi T,Suzuki S,Fuchimoto D,Sembon S,Furusawa T,Liu D,Nagasaka T,Kuzuya T,Ogawa H,Yamamoto K,Iwasaki K,Haneda M,Maruyama S,Kobayashi T

    更新日期:2012-03-01 00:00:00

  • Functionally and phenotypically mature mouse CD8+ T cells develop in porcine thymus grafts in mice.

    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

    authors: Zhao Y,Barth RN,Swenson K,Pearson DA,Sykes M

    更新日期:1998-02-01 00:00:00

  • Pre-transplant blood transfusion induces tolerance to hamster cardiac xenografts in athymic nude rats.

    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

    authors: Vriens PW,Stoot JH,Hoyt G,Scheringa M,Bouwman E,Robbins RC

    更新日期:2001-11-01 00:00:00

  • Circulating pig-specific DNA as a novel biomarker for monitoring xenograft rejection.

    abstract::Monitoring for immune rejection is crucial for long-term survival of pig xenografts. Circulating DNA is a promising non-invasive biomarker for either organ injury or response to therapy. In this study, circulating pig-specific DNA (cpsDNA) was monitored during xenograft rejection. Potential targets of cpsDNA were sele...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12522

    authors: Zhou M,Lu Y,Zhao C,Zhang J,Cooper DKC,Xie C,Song Z,Gao H,Qu Z,Lin S,Deng Y,Hara H,Zhan Y,Jiang Z,Dai Y,Wu C,Cai Z,Mou L

    更新日期:2019-07-01 00:00:00

  • Cytokine-inducible promoters to drive dynamic transgene expression: The "Smart Graft" strategy.

    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

    authors: Fischer A,Manske K,Seissler J,Wohlleber D,Simm N,Wolf-van Buerck L,Knolle P,Schnieke A,Fischer K

    更新日期:2020-11-01 00:00:00

  • Cold storage of porcine hepatocyte spheroids for spheroid bioartificial liver.

    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

    authors: Li Y,Chen HS,Shaheen M,Joo DJ,Amiot BP,Rinaldo P,Nyberg SL

    更新日期:2019-07-01 00:00:00

  • Cyclophosphamide, but not CTLA4Ig, prolongs survival of fetal pig islet grafts in anti-T cell monoclonal antibody-treated NOD mice.

    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

    authors: Koulmanda M,Kovarik J,Mandel TE

    更新日期:1998-08-01 00:00:00

  • Heart transplantation across antibodies against human leukocyte antigen and ABO-post-transplant follow-up of donor reactive antibodies.

    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

    authors: Bućin D,Johansson S,Lindberg LO

    更新日期:2006-03-01 00:00:00

  • Impaired spinal cord remyelination by long-term cultured adult porcine olfactory ensheathing cells correlates with altered in vitro phenotypic properties.

    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

    authors: Radtke C,Lankford KL,Wewetzer K,Imaizumi T,Fodor WL,Kocsis JD

    更新日期:2010-01-01 00:00:00

  • Immortalization of porcine hepatocytes with a α-1,3-galactosyltransferase knockout background.

    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

    authors: Wang Q,Zhang X,Wang B,Bai G,Pan D,Yang P,Tao K,Li X,Dou K

    更新日期:2020-01-01 00:00:00

  • T-cell responses during pig-to-primate xenotransplantation.

    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

    authors: Davila E,Byrne GW,LaBreche PT,McGregor HC,Schwab AK,Davies WR,Rao VP,Oi K,Tazelaar HD,Logan JS,McGregor CG

    更新日期:2006-01-01 00:00:00

  • Identification of soluble and membrane-bound isoforms of porcine tumor necrosis factor receptor 2.

    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

    authors: Uribe-Herranz M,Casinghino SR,Bosch-Presegué L,Fodor WL,Costa C

    更新日期:2011-03-01 00:00:00

  • Rat-to-mouse small bowel xenotransplantation: a novel model for studying acute vascular and hyperacute xenograft rejection and xenogenic cell migration.

    abstract::The present study was undertaken to establish a rat-to-mouse vascularized small bowel xenotransplantation model to study acute vascular and hyperacute xenograft rejection, and xenogenic cell migration. Lewis rat small bowel grafts were transplanted heterotopically to group 1, Balb/c mice, and group 2, Balb/c mice pre-...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.1999.00001.x

    authors: Kiyochi H,Kellersmann R,Blömer A,Garcia BM,Zhang Z,Zhong R,Grant DR

    更新日期:1999-02-01 00:00:00

  • Investigation of potential carbohydrate antigen targets for human and baboon antibodies.

    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

    authors: Yeh P,Ezzelarab M,Bovin N,Hara H,Long C,Tomiyama K,Sun F,Ayares D,Awwad M,Cooper DK

    更新日期:2010-05-01 00:00:00