Pig islet xenografts are resistant to autoimmune destruction by non-obese diabetic recipients after anti-CD4 treatment.

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-obese diabetic (NOD) recipients rejected isografts rapidly whether or not the recipients were depleted of CD4+ T-cells. Young NOD mice made diabetic with streptozotocin accepted islet isografts without immunosuppression, indicating that destructive autoimmunity did not develop in these recipients. Pig xenografts were rejected equally quickly in the two types of NOD recipients in the absence of immunosuppression and survived for up to 9 weeks in both types of NOD recipients after CD4 depletion. BALB/c mice often accepted pig xenografts indefinitely after anti-CD4 antibody treatment. These results suggest that pig islets are resistant to recurrent autoimmunity when CD4+ T-cells are depleted. The difficulty in obtaining indefinite islet xenograft survival in NOD recipients occurs independently from the development of destructive autoimmunity.

journal_name

Xenotransplantation

journal_title

Xenotransplantation

authors

Koulmanda M,Qipo A,Smith RN,Auchincloss H Jr

doi

10.1034/j.1399-3089.2003.02040.x

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

178-84

issue

2

eissn

0908-665X

issn

1399-3089

pii

2o040

journal_volume

10

pub_type

杂志文章
  • T-cell-mediated immunological barriers to xenotransplantation.

    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

    authors: Scalea J,Hanecamp I,Robson SC,Yamada K

    更新日期:2012-01-01 00:00:00

  • Microcirculatory alterations after orthotopic pig-to-baboon heart transplantation.

    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

    authors: Bauer A,Renz V,Baschnegger H,Abicht JM,Beiras-Fernandez A,Brenner P,Thein E,Schmoeckel M,Reichart B,Christ F

    更新日期:2011-07-01 00:00:00

  • Diabetes induction by total pancreatectomy in minipigs with simultaneous splenectomy: a feasible approach for advanced diabetes research.

    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

    authors: Heinke S,Ludwig B,Schubert U,Schmid J,Kiss T,Steffen A,Bornstein S,Ludwig S

    更新日期:2016-09-01 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

  • 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

  • Jewish, Christian and Muslim theological perspectives about xenotransplantation.

    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

    authors: Paris W,Seidler RJH,FitzGerald K,Padela AI,Cozzi E,Cooper DKC

    更新日期:2018-05-01 00:00:00

  • Acceptance of organ xenotransplantation among Latin American immigrants resident in the United States.

    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

    authors: Ríos A,López-Navas AI,Martínez-Alarcón L,Ramis G,Hernández AM,Ayala MA,Garrido G,Ramírez P,Parrilla P

    更新日期:2016-07-01 00:00:00

  • The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 1: Key ethical requirements and progress toward the definition of an international re

    abstract::The outstanding results recently obtained in islet xenotransplantation suggest that porcine islet clinical trials may soon be scientifically appropriate. Before the initiation of such clinical studies, however, it is essential that a series of key ethical and regulatory conditions are satisfied. As far as ethics is co...

    journal_title:Xenotransplantation

    pub_type: 共识发展会议,杂志文章

    doi:10.1111/j.1399-3089.2009.00540.x

    authors: Cozzi E,Tallacchini M,Flanagan EB,Pierson RN 3rd,Sykes M,Vanderpool HY

    更新日期:2009-07-01 00:00:00

  • Increased human tumor necrosis factor-α levels induce procoagulant change in porcine endothelial cells in vitro.

    abstract:BACKGROUND:Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strate...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2012.00704.x

    authors: Lee KG,Lee H,Ha JM,Lee YK,Kang HJ,Park CG,Kim SJ

    更新日期:2012-05-01 00:00:00

  • Donor-derived infections and infectious risk in xenotransplantation and allotransplantation.

    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

    authors: Nellore A,Fishman JA

    更新日期:2018-07-01 00:00:00

  • The effect of soluble complement receptor type 1 on acute humoral xenograft rejection in hDAF-transgenic pig-to-primate life-supporting kidney xenografts.

    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

    authors: Lam TT,Hausen B,Hook L,Lau M,Higgins J,Christians U,Jacobsen W,Baluom M,Duthaler R,Katopodis A,Chavez G,Cozzi E,Harrison R,Schuurman HJ,Borie D,Morris RE

    更新日期:2005-01-01 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

  • Adult porcine islets produce MCP-1 and recruit human monocytes in vitro.

    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

    authors: Ehrnfelt C,Kumagai-Braesch M,Uzunel M,Holgersson J

    更新日期:2004-03-01 00:00:00

  • Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand.

    abstract::Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine-based approach termed "semi-xenotransplantation" (SX) seeks...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1111/xen.12122

    authors: Salvatori M,Peloso A,Katari R,Soker S,Lerut JP,Stratta RJ,Orlando G

    更新日期:2015-01-01 00:00:00

  • Systemic immune modulation using chemokine receptor 7 expressing porcine Sertoli cells.

    abstract:BACKGROUND:Sertoli cells (SC) are known to have active mechanism for evading humoral immune response and are known to have immune modulatory effects in the presence of other antigens. This has led us to hypothesize that systemic immune modulating effect of SC might be optimized by their residence on peripheral lymph no...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/j.1399-3089.2007.00435.x

    authors: Lee HM,Lim HG,Oh BC,Park CS,Lee DS,Lee JR

    更新日期:2007-11-01 00:00:00

  • Efficiency of porcine endothelial cell infection with human cytomegalovirus depends on both virus tropism and endothelial cell vascular origin.

    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

    authors: Millard AL,Häberli L,Sinzger C,Ghielmetti M,Schneider MK,Bossart W,Seebach JD,Mueller NJ

    更新日期:2010-07-01 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

  • Coagulation biomarkers in healthy male Cynomolgus macaque monkeys (Macaca fascicularis).

    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

    authors: Rhu J,Lee KW,Kim KS,Lee JS,Kim SJ,Park JB

    更新日期:2019-01-01 00:00:00

  • Role of P-selectin and P-selectin glycoprotein ligand-1 interaction in the induction of tissue factor expression on human platelets after incubation with porcine aortic endothelial cells.

    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

    authors: Ezzelarab MB,Liu YW,Lin CC,Long C,Ayares D,Dorling A,Cooper DK

    更新日期:2014-01-01 00:00:00

  • Epigenetic biomarkers indicate islet cell death in xenotransplantation.

    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

    authors: Faulk C,Mueller KR,Cheishvili D,Colwell M,Pepin AS,Syzf M,Hering BJ,Burlak C

    更新日期:2020-03-01 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

  • 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

  • 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

  • Understanding of and attitude to xenotransplantation among Italian university students: impact of a 3-yr university course.

    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

    authors: Canova D,De Bona M,Rumiati R,Masier A,Ermani M,Naccarato R,Cozzi E,Ancona E,Burra P

    更新日期:2006-05-01 00:00:00

  • IXA Honorary Member Lecture, 2017: The long and winding road to tolerance.

    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

    authors: Sykes M

    更新日期:2018-05-01 00:00:00

  • Atrase B, a novel metalloprotease with anti-complement and anti-coagulant activity, significantly delays discordant cardiac xenograft rejection.

    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

    authors: Fu C,Shi L,Huang X,Feng H,Tan X,Chen S,Zhu L,Sun Q,Chen G

    更新日期:2020-09-01 00:00:00

  • Role of anti-CD40 antibody-mediated costimulation blockade on non-Gal antibody production and heterotopic cardiac xenograft survival in a GTKO.hCD46Tg pig-to-baboon model.

    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

    authors: Mohiuddin MM,Singh AK,Corcoran PC,Hoyt RF,Thomas ML 3rd,Lewis BG,Eckhaus M,Dabkowski NL,Belli AJ,Reimann KA,Ayares D,Horvath KA

    更新日期:2014-01-01 00:00:00

  • Co-stimulation blockade targeting CD154 and CD28/B7 modulates the induced antibody response after a pig-to-baboon cardiac xenograft.

    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

    authors: Wu G,Pfeiffer S,Schröder C,Zhang T,Nguyen BN,Lea W,Kelishadi S,Atkinson JB,Schuurman HJ,White DJ,Azimzadeh AM,Pierson RN 3rd

    更新日期:2005-05-01 00:00:00

  • Comparison of allogeneic and xenogeneic in vitro T-cell proliferative responses in sensitized patients awaiting kidney transplantation.

    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. W...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2003.00089.x

    authors: Oostingh GJ,Davies HF,Bradley JA,Taylor CJ

    更新日期:2003-11-01 00:00:00

  • Islet cell xenotransplantation: a serious look toward the clinic.

    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

    authors: Samy KP,Martin BM,Turgeon NA,Kirk AD

    更新日期:2014-05-01 00:00:00