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

Lam, Tina I.; Hausen, Bernard; Hook, Laura; Lau, M; Higgins, Julian P T; Christians, Uwe; Jacobsen, Wolfgang; Baluom, Muhammad; Duthaler, Rudolf O.; Katopodis, Andreas; Chavez, Gilda; Cozzi, Emanuele; Harrison, Richard A.; Schuurman, Henk‐Jan; Borie, Dominique C.; Morris, Randall E.

doi:10.1111/j.1399-3089.2004.00184.x

Cited by 28 publications

(19 citation statements)

References 35 publications

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“…Experimental xenotransplantation returned in the 1960s and ushered an increased awareness of humoral rejection [132]. With improved understanding of the role of xenoreactive antibodies and complement, hyperacute rejection became preventable by inhibiting complement activation and removing offending antibodies or altering their targets, namely Gal 1,3 Gal in the pig-to-NHP model [133–135]. The resulting “delayed” acute humoral rejection also involved xenoreactive antibodies against Gal as well as other components of the donor xenograft.…”

Section: B Cells In Animal Model Of Chronic Rejectionmentioning

confidence: 99%

The role of B cells in solid organ transplantation

Kwun

Bulut

Kim

et al. 2012

Seminars in Immunology

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The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

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Section: B Cells In Animal Model Of Chronic Rejectionmentioning

confidence: 99%

The role of B cells in solid organ transplantation

Kwun

Bulut

Kim

et al. 2012

Seminars in Immunology

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“…Lam et al [9] carried out hDAF pig kidney transplants in cynomolgus monkeys and documented that, although GAS914 effectively neutralized circulating anti-Gal antibodies, AHXR eventually developed in most cases. Complement deposition was largely prevented by treatment with soluble complement receptor type 1, although this did not significantly increase xenograft survival.…”

Section: Kidney Transplantsmentioning

confidence: 98%

Pig-to-nonhuman primate organ xenotransplantation

Ezzelarab

Yamada

Cooper

et al. 2005

Current Opinion in Organ Transplantation

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“…Transgenic animal models for human xeno transplantation remain a promising option for overcoming severe donor organ shortages. Researchers all over the world will continue to address the biological barriers that are yet to be removed (Lam, 2005;Yamada, 2005).Transgenic animals have been widely used for the study of basic and mechanistic research and to study physiological processes, but their use in safety evaluation studies is minimal. Researchers look forward that with the recent drafting of an Organisation for Economic Co-operation and Development (OECD) guideline for transgenic rodent mutation assay (Lamber et al, 2008), the transgenic mouse models in combination with the traditional 2-year cancer bioassay in rats (EC, 2006;Wells and Williams, 2009), and other advancements, there will be a more active use of transgenic animals for toxicity/safety evaluation studies and hence for the risk assessment programme.Tg26 HIVAN mouse model was the first transgenic model developed in 1991 to study Human Immuno Deficiency Virus (HIV) ( Rosential et al, 2009).…”

Section: Transgenic /Knock Out/ Knock In Animals Gene Manipulation Tementioning

confidence: 99%

Relevance of Small Laboratory Animals as Models in Translational Research: Challenges and Road Ahead

Siddiqui¹,

Jagdale²,

Ahire³

et al. 2016

J App Pharm Sci

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Translational research using small laboratory animals is being done to demonstrate proof of concept, to study pharmacokinetics as well as to understand efficacy and safety of new drug molecules. During the evaluation of a drug candidate, the assessment of efficacy and safety is normally performed in different experiments using various animal models. In such experiments, efficacy is assessed by mimicking the disease state in animal model while safety is investigated in healthy animals. Inventing new drugs using biotechnological and nanotechnological approaches is becoming a major thrust area in drug research. Apart from this, the development of medicine from traditional knowledge like Ayurveda has emerged as major area for drug industry. Use of conventional in-vivo approaches may not prove useful to answer many questions. Transgenic/knock-out/knock-in animals are now getting space in pharmaceutical research for target identification and validation. Predictability of in-vivo research depends on scientific protocols and methods adopted for model selection and development. Various alternative approaches for in-vivo research are being followed. It is a fact that no animal model is 100 % capable of mimicking the complex human body but still, researchers have not yet found any alternative model which can completely replace in -vivo models. This review is a holistic approach explaining the various animal models being used for translational research, animal ethical issues, alternative approaches available and provides a critical analysis of major issues/challenges faced in translational research using in-vivo approaches.

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

Cited by 28 publications

References 35 publications

The role of B cells in solid organ transplantation

The role of B cells in solid organ transplantation

Pig-to-nonhuman primate organ xenotransplantation

Relevance of Small Laboratory Animals as Models in Translational Research: Challenges and Road Ahead

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