The generation of transgenic pigs as potential organ donors for humans

Cozzi, Emanuele; White, David J.

doi:10.1038/nm0995-964

Cited by 562 publications

(281 citation statements)

References 18 publications

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“…Initial work with mouse and rat cell lines transfected with cDNAs of these molecules showed significant protection of the transfected cells to the effects of human serum Oglesby et al 1992;Walsh et al 1991). This was followed by experiments with transgenic mice and pigs that confirm the role of these molecules in protecting heterologous animal tissue from human serum attack, even in the context of ex vivo and in vivo models of xenotransplantation (McCurry et al 1995;Fodor et al 1994;Cozzi & White 1995;White et al submitted). While this work provides important proof of function for the use of these molecules in discordant xenotransplantation, it remains short of providing complete animal models for study.…”

Section: Introductionmentioning

confidence: 96%

A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection

et al. 1996

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Background: In recent years, interest has been revived in the possibility of transplanting organs into humans from a phylogenetically disparate species such as the pig (xenotransplantation). Such discordant xenografts, however, are subject to hyperacute rejection (HAR) and activation of host complement plays a major role in this rejection. This problem may be solved through the use of transgenic technology by providing the grafted tissue with molecules that down-regulate the action of host complement.

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Section: Introductionmentioning

confidence: 96%

A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection

et al. 1996

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“…Recent progress in the development of transgenic donor organs [7] has led to a renewed interest in xenotransplantation as a possible solution for the current donor organ shortage. Among the different species under consideration as suitable organ donors, pigs are the most likely donor animals [5, 61. Currently, the potential for infection of xeno-organ recipients with xenozoonoses and, especially, the subsequent risk of transmission of any infective agent from the xenotransplant recipient to the general population are major concerns [l, 2, 4, 291.…”

Section: Introductionmentioning

confidence: 99%

Analysis of potential porcine endogenous retrovirus (PERV) transmission in a whole-organ xenotransplantation model without interfering microchimerism

Loss¹,

Arends²,

Winkler³

et al. 2001

Transplant International

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The question whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for the evaluation of the safety of pigto-man xenotransplantation. Unfortunately, polymerase chain reaction (PCR)-based analysis of potential PERV infections in nonhuman-primate whole-organ xenotransplantation models is hampered by false positive results due to chimeric porcine cells. To avoid the inherent analytical problem of xenomicrochimerism, we developed a non-life-supporting pig-to-primate kidney xenotransplantation model: porcine kidneys were transplanted, whereas the functioning recipient kidneys remained in situ. Subsequent to rejection (after 2 hours to 15 days), xenografts were removed, and recipients remained alive for up to 287 days. Immunosuppressive therapy based on cyclophosphamide, cyclosporine, and steroids was maintained for 28 days after transplantation. Using appropriate PCR assays, xenochimerism was found in tissue samples and partly even in peripheral blood leukocytes (PBLs) while the porcine kidneys were in situ. After graft removal, xenochimerism was no longer detectable, thus allowing analysis for possible PERV transmission.

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“…Briefly, fresh splenocytes were suspended in NS-1 medium (RPMI1640 containing 10% FCS, 2 mM glutamine, 1 mM sodium pyruvate, 50 IU/ml penicillin and 50 µg/ml streptomycin) and centrifuged at 400 g for 5 min at room temperature (RT). The cells were treated with 0.83% NH 4 Cl-Tris (pH 7.6) followed by washing twice with NS-1 medium and resuspended in NS-1 medium.…”

Section: Production Of Recombinant Pil-4 By E Coli and Baculovirusmentioning

confidence: 99%

“…Further, the pig is a useful model for human diseases such as infectious diseases and immune-mediated diseases [8,18]. In addition, xenograft is intensively studied and the pig is a hopeful candidate for an alternative source of tissues for humans [4]. Thus, assessment of porcine immune system including Th1/ Th2 profile is beneficial to both pigs and humans.…”

mentioning

confidence: 99%

Production and Characterization of Monoclonal Antibodies against Porcine Interleukin-4

Ishikura

Kato

Hashimoto

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. Interleukin 4 (IL-4) is an important regulatory cytokine produced by activated T lymphocytes and mast cells, and regulates the growth and differentiation of cells such as B and T lymphocytes. In the present study, recombinant thioredoxin (Trx)-porcine IL-4 (pIL-4) fusion protein was prepared by Escherichia coli (E. coli), and by using this protein as an immunogen, monoclonal antibodies (mAbs) against pIL-4 were produced to establish a basis for a research on immune responses in pigs. Six stable hybridoma cell lines were successfully established and specific binding of each mAb to recombinant pIL-4 produced by E. coli and insect cells infected with recombinant baculovirus was shown by enzyme-linked immunosorbent assay (ELISA) and/or immunoblot analysis. Isotype analyses of these mAbs revealed that the subclass of 5 out of 6 mAbs was IgG1 and the rest was IgG2b. Further, assessment of their epitopes by competition binding assay indicated that the mAbs obtained in this study bound to 4 different epitopes. The recombinant proteins and mAbs produced in this study will be useful tools for the assessment of porcine immune system.

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The generation of transgenic pigs as potential organ donors for humans

Cited by 562 publications

References 18 publications

A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection

A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection

Analysis of potential porcine endogenous retrovirus (PERV) transmission in a whole-organ xenotransplantation model without interfering microchimerism

Production and Characterization of Monoclonal Antibodies against Porcine Interleukin-4

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