Potential of Heterotopic Cardiac Transplantation in Mice as a Model for Elucidating Mechanisms of Graft Rejection

Laschinger, Melanie; Aßfalg, Volker; Matevossian, Edouard; Friess, Helmut; Hüser, Norbert

doi:10.5772/27394

Cited by 2 publications

(5 citation statements)

References 44 publications

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“…Additionally, in the human heart, the coronaries are located on the surface, embedded in epicardial fat, and epicardial fat produces proinflammatory cytokines including IL-6, IL-8, and MCP 1. In contrast to humans, in mice, only the first few millimeters of the coronary arteries are on the surface of the heart, and after that short distance, they pass through the myocardium [67,70].…”

Section: Heart Transplantationmentioning

confidence: 93%

“…During this procedure, the heart of the donor animal is explanted and transplanted heterotopically into the abdomen of the recipient animal with the donor's ascending aorta anastomosed to the recipients infrarenal aorta, and the donor's pulmonary artery anastomosed to the recipient's inferior vena cava [41,[65][66][67]. This recipient surgical procedure can also be performed using cervical vessels.…”

Section: Heart Transplantationmentioning

confidence: 99%

“…Animal death at or before day three is considered to be a technical failure [63]. Especially, the analysis of rejection processes in different mouse strains with defined genetic backgrounds offers the unique possibility to gain a deeper insight into immune interactions between receptors and ligands and their effect on physiological and pathophysiological mechanisms of acute and chronic graft rejection [67].…”

Section: Heart Transplantationmentioning

confidence: 99%

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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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Section: Heart Transplantationmentioning

confidence: 93%

Section: Heart Transplantationmentioning

confidence: 99%

Section: Heart Transplantationmentioning

confidence: 99%

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Animal Models in Allogenic Solid Organ Transplantation

Wenzel¹,

Blasczyk²,

Figueiredo³

2021

Transplantology

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“…For the chronic rejection model, WT, IL-21-/-, and BATF-/- recipient mice received low immunogenicity heart transplants from B6 bm12 donor mice. Heart transplants were performed as previously described[16]. Briefly, the heart was excised from the donor, and all vessels to and from the heart were tied off with surgical sutures in 10–0 silk except for the ascending aorta and the pulmonary artery.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, the heart was excised from the donor, and all vessels to and from the heart were tied off with surgical sutures in 10–0 silk except for the ascending aorta and the pulmonary artery. The ascending aorta of the graft was sutured in to the abdominal aorta of the recipient while the pulmonary artery of the graft was sutured in to the inferior vena cava of the recipient[16].…”

Section: Methodsmentioning

confidence: 99%

Interleukin 21 (IL-21) regulates chronic allograft vasculopathy (CAV) in murine heart allograft rejection

et al. 2019

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IL-21 is the most recently discovered common gamma-chain cytokine that promotes persistent T-cell responses in chronic infections, autoimmunity and cancer. However, the therapeutic potential of inhibiting the IL-21-BATF signaling axis, particularly in transplant rejection, remains unclear. We used heart transplant models to examine the effects of IL-21 blockade in prevention of chronic cardiac allograft vasculopathy (CAV) using genetic knock-out and therapeutic approaches. Both wild-type C57BL/6 and IL-21-/- strains acutely rejected Balb/c skin grafts and once immunized with this skin graft, rejected Balb/c heart allografts in an accelerated fashion. However, when transplanted with heart grafts from the class-II major histocompatibility complex mutant, B6bm12 mice; wild-type recipients developed CAV, while IL-21-/- recipients were protected, even at day 100 post-transplant. Similarly, BATF-/- recipients, lacking the transcription factor BATF responsible for IL-21 production, did not develop CAV in B6-bm12 heart allografts. Strikingly, in a transient treatment protocol, the development of CAV in wild-type recipients of B6-bm12 hearts allografts was blocked by the administration of IL-21 receptor fusion protein (R-Fc). Thus, we demonstrate that CAV is regulated at least in part by IL-21 signaling and its blockade by genetic approaches or therapy with IL-21R-Fc prevents CAV in mice.

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Potential of Heterotopic Cardiac Transplantation in Mice as a Model for Elucidating Mechanisms of Graft Rejection

Cited by 2 publications

References 44 publications

Animal Models in Allogenic Solid Organ Transplantation

Animal Models in Allogenic Solid Organ Transplantation

Interleukin 21 (IL-21) regulates chronic allograft vasculopathy (CAV) in murine heart allograft rejection

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