Small Animal Models of Transplantation

Gunaratnam, Lakshman; Jevnikar, Anthony M.; Mannon, Roslyn B.

doi:10.1002/9781118873434.ch14

Cited by 4 publications

(5 citation statements)

References 477 publications

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“…Although there are practical limitations involving solid organ transplantation, such as a limited number of donors, the understanding of the biology of rejection remains an essential component for improving the efficacy of these procedures, as well as reducing the potential morbidity of immunosuppression. Lab animal models remain a valuable tool for investigating the biology of allo‐transplantation, rejection and tolerance . The mouse model has been particularly appropriate for this area of investigation due to an in‐depth understanding of its genome, as well as the availability of syngeneic and transgenic species to aid in the study of the immunology of transplantation .…”

Section: Introductionmentioning

confidence: 99%

A new method for skin grafting in murine model

Pakyari

Farokhi

Khosravi‐Maharlooei

et al. 2016

Wound Repair Regeneration

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Skin transplantation provides an excellent potential model to investigate the immunology of allograft rejection and tolerance induction. Despite the theoretical ease of performing skin transplantation, as well as the potential of directly observing the reaction to the transplanted tissue, the poor reliability of skin transplantation in the mouse has largely precluded the use of this model. Furthermore, there is controversy regarding the most appropriate skin graft donor site due to poor success of back skin transplantation, as compared with the thinner ear or tail skin. This study demonstrates a reliable method to successfully perform skin grafts in a mouse model, as well as the clinical and histologic outcome of syngeneic grafts. A total of 287 grafts were performed (in 126 mice) utilizing donor skin from the ear, tail or back. No graft failure or postoperative mortality was observed. Comparison of this technique with two previously established protocols of skin transplantation (5.0 absorbable Suture + tissue glue technique and no-suture technique) demonstrates the significant improvement in the engraftment success of the new technique. In summary, a new technique for murine skin grafting demonstrates improved reliability across donor site locations and strains, increasing the potential for investigating interventions to alter the rejection process.

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Section: Introductionmentioning

confidence: 99%

A new method for skin grafting in murine model

Pakyari

Farokhi

Khosravi‐Maharlooei

et al. 2016

Wound Repair Regeneration

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“…The artificial Rag2 −/− model used to identify a tissue-independent signature of ACAR (Figs. 1 to 5) enabled graft integration and allowed a focus on rejection without potential interference from wound healing dynamics yet also has altered endogenous T cell processes (e.g., central tolerance, proliferation, migration, and, possibly, activation) (60,61) and avoided the IRI period immediately following transplantation, a period of great clinical need for surveilling early rejection (8,54) and distinguishing nonrejection graft dysfunction (49, 62) (e.g., cardiomyopathies). In these wild-type STx with varied doses of transient T cell depletion (Fig.…”

Section: Scaffolds Predict Onset Of Acar Graft Injury In Immune Suppr...mentioning

confidence: 99%

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts

Urie,

Morris,

Farris

et al. 2024

Sci. Adv.

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Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2 −/− mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.

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“…Mice have always played an important role in a variety of disease models not only because of the extensive knowledge of their immune system and the possibility of genetical modification but also because of the immense availability of specific reagents. Mice as recipients and donors contributed significantly toward the understanding of the mechanisms of rejection and innate immune injury [10].…”

Section: Small Animal Modelsmentioning

confidence: 99%

“…The understanding of the basic correlations of the immune response has been discovered in animal experiments. These experiments helped to provide a deep insight into the mechanisms of transplant immunology, rejection, and the modus operandi of immunosuppression as well as the opportunity to refine and develop surgical techniques [10].…”

Section: Introductionmentioning

confidence: 99%

Animal Models in Allogenic Solid Organ Transplantation

Wenzel¹,

Blasczyk²,

Figueiredo³

2021

Transplantology

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Animal models provide the link between in vitro research and the first in-man application during clinical trials. They provide substantial information in preclinical studies for the assessment of new therapeutic interventions in advance of human clinical trials. However, each model has its advantages and limitations in the ability to imitate specific pathomechanisms. Therefore, the selection of an animal model for the evaluation of a specific research question or evaluation of a novel therapeutic strategy requires a precise analysis. Transplantation research is a discipline that largely benefits from the use of animal models with mouse and pig models being the most frequently used models in organ transplantation research. A suitable animal model should reflect best the situation in humans, and the researcher should be aware of the similarities as well as the limitations of the chosen model. Small animal models with rats and mice are contributing to the majority of animal experiments with the obvious advantages of these models being easy handling, low costs, and high reproductive rates. However, unfortunately, they often do not translate to clinical use. Large animal models, especially in transplantation medicine, are an important element for establishing preclinical models that do often translate to the clinic. Nevertheless, they can be costly, present increased regulatory requirements, and often are of high ethical concern. Therefore, it is crucial to select the right animal model from which extrapolations and valid conclusions can be obtained and translated into the human situation. This review provides an overview in the models frequently used in organ transplantation research.

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Small Animal Models of Transplantation

Cited by 4 publications

References 477 publications

A new method for skin grafting in murine model

A new method for skin grafting in murine model

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts

Animal Models in Allogenic Solid Organ Transplantation

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