Real-time assessment of encapsulated neonatal porcine islets prior to clinical xenotransplantation.

Abstract:

BACKGROUND:Porcine islet transplantation is emerging as an attractive option for the treatment of patients with type 1 diabetes, with the possibility of providing islets of higher and more consistent quality and in larger volumes than available from human pancreata. The use of encapsulated neonatal porcine islets (ENPI) is appealing because it can address islet supply limitations while reducing the need for anti-rejection therapy. Pre-transplant characterization of ENPI viability and potency is an essential component of the production process. We applied the validated assay for oxygen consumption rate normalized for DNA content (OCR/DNA) to characterize ENPI viability. METHODS:ENPI of low viscosity and high m alginate were prepared according to standard methods and characterized at various culture time points up to 5 weeks. RESULTS:The OCR/DNA (nmol/min·mgDNA ± SEM) of ENPI (235 ± 10, n = 9) was comparable to that of free NPI (255 ± 14, n = 13). After encapsulation, NPI OCR/DNA was sustained over a culture period of up to 5 weeks. The average OCR/DNA of ENPI cultured longer than 9 days was higher than that of freshly encapsulated NPI. CONCLUSION:This is the first characterization of ENPI by a validated and more sensitive method for product viability. The NPI encapsulation process does not compromise viability as measured by OCR/DNA, and ENPI can be cultured for up to 5 weeks with maintenance of viability. ENPI meet or exceed current adult porcine islet product release criteria (established at the University of Minnesota) for preclinical xenotransplantation in terms of OCR/DNA.

journal_name

Xenotransplantation

journal_title

Xenotransplantation

authors

Kitzmann JP,Law L,Shome A,Muzina M,Elliott RB,Mueller KR,Schuurman HJ,Papas KK

doi

10.1111/xen.12005

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

333-6

issue

6

eissn

0908-665X

issn

1399-3089

journal_volume

19

pub_type

杂志文章
  • Molecular and functional characterization of porcine LFA-1 using monoclonal antibodies to CD11a and CD18.

    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

    authors: Alvarez B,Doménech N,Alonso F,Sánchez C,Gómez del Moral M,Ezquerra A,Domínguez J

    更新日期:2000-11-01 00:00:00

  • Glucose metabolism in pigs expressing human genes under an insulin promoter.

    abstract:BACKGROUND:Xenotransplantation of porcine islets can reverse diabetes in non-human primates. The remaining hurdles for clinical application include safe and effective T-cell-directed immunosuppression, but protection against the innate immune system and coagulation dysfunction may be more difficult to achieve. Islet-ta...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12145

    authors: Wijkstrom M,Bottino R,Iwase H,Hara H,Ekser B,van der Windt D,Long C,Toledo FG,Phelps CJ,Trucco M,Cooper DK,Ayares D

    更新日期:2015-01-01 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

  • 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

  • Presence of Gal-alpha1,3Gal epitope on xenogeneic lines: implications for cellular gene therapy based on the encapsulation technology.

    abstract::Exposure to human serum induces the lysis of xenogeneic cells through natural antibodies and complement activation. The carbohydrate Galactose-alpha1,3-Galactose (Gal-alpha1,3-Gal) epitope, has been shown to be the principal antigenic determinant on target cells. This reaction is, therefore, particularly important for...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1034/j.1399-3089.2003.00110.x

    authors: Déglon N,Aubert V,Spertini F,Winkel L,Aebischer P

    更新日期:2003-05-01 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • Financial aspects of organ procurement from deceased donors in the USA-Relevance to xenotransplantation.

    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

    authors: Saari RJ,Cooper DKC

    更新日期:2017-07-01 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

  • 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

  • Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand.

    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

    authors: Wynyard S,Nathu D,Garkavenko O,Denner J,Elliott R

    更新日期:2014-07-01 00:00:00

  • The usefulness and limitations of the diabetic macaque model in evaluating long-term porcine islet xenograft survival.

    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

    authors: Graham ML,Schuurman HJ

    更新日期:2013-01-01 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

  • Address by the Honorary Founding President of the Xenotransplantation Society. The eye of an eagle: xenobiology and the quest for bioadvantage.

    abstract::My purpose in these remarks is to stimulate us to consider the vast array that nature has provided us in the differentiation of species, and to examine the possibility that some of these differences might prove useful in other species, including man. ...

    journal_title:Xenotransplantation

    pub_type:

    doi:10.1034/j.1399-3089.2000.00045.x

    authors: Reemtsma K

    更新日期:2000-05-01 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

  • Pre-clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique.

    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

    authors: Abicht JM,Mayr T,Reichart B,Buchholz S,Werner F,Lutzmann I,Schmoeckel M,Bauer A,Thormann M,Langenmayer M,Herbach N,Pohla H,Herzog R,McGregor CG,Ayares D,Wolf E,Klymiuk N,Baehr A,Kind A,Hagl C,Ganswindt U,Belka C

    更新日期:2015-11-01 00:00:00

  • Characterization of porcine endogenous retrovirus expression in neonatal and adult pig pancreatic islets.

    abstract:BACKGROUND:Pig islets represent an alternative to the current modes of treatment for patients with diabetes. However, the concerns over pathogen transmission including that of PERV limit their immediate, widespread usage in humans. It has been previously demonstrated that PERV copy number and particularly expression le...

    journal_title:Xenotransplantation

    pub_type: 杂志文章

    doi:10.1111/xen.12311

    authors: Mourad NI,Crossan C,Cruikshank V,Scobie L,Gianello P

    更新日期:2017-07-01 00:00:00

  • Pig endogenous retroviruses and xenotransplantation.

    abstract::Xenotransplantation of porcine organs might provide an unlimited source of donor organs to treat endstage organ failure diseases in humans. However, pigs harbour retroviruses with unknown pathogenic potential as an integral part of their genome. While until recently the risk of interspecies transmission of these porci...

    journal_title:Xenotransplantation

    pub_type: 杂志文章,评审

    doi:10.1034/j.1399-3089.2002.01110.x

    authors: Blusch JH,Patience C,Martin U

    更新日期:2002-07-01 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

  • Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection.

    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

    authors: Li P,Estrada JL,Burlak C,Montgomery J,Butler JR,Santos RM,Wang ZY,Paris LL,Blankenship RL,Downey SM,Tector M,Tector AJ

    更新日期:2015-01-01 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

  • Absence of humoral and cellular alloreactivity in baboons sensitized to pig antigens.

    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

    authors: Baertschiger RM,Dor FJ,Prabharasuth D,Kuwaki K,Cooper DK

    更新日期:2004-01-01 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

  • 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