Cellular Immunotherapies in Preclinical Large Animal Models of Transplantation

Matar, Abraham J.; Crepeau, Rebecca L.; Duran‐Struuck, Raimon

doi:10.1016/j.bbmt.2020.09.032

Cited by 4 publications

(5 citation statements)

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“…Such cell populations target specific immunologic pathways linked with allograft rejection and off-target systemic side effects ( 28 ). In preclinical VCA models, T regs ( 29 ), CAR-T cells ( 30 , 31 ), MSCs ( 32 , 33 ), and RMCs ( 34 ) have demonstrated to improve allograft acceptance and minimize systemic toxicity.…”

Section: Cellular Therapeutic Strategies In Transplantation Patientsmentioning

confidence: 99%

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Knoedler,

Dean,

Diatta

et al. 2024

Front. Immunol.

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Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery.

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Section: Cellular Therapeutic Strategies In Transplantation Patientsmentioning

confidence: 99%

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Knoedler,

Dean,

Diatta

et al. 2024

Front. Immunol.

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“…Large animal models include sheep, goats, cows, pigs, horses, dogs, and primates. Among these, the most commonly used species are canines, swine, and nonhuman primates (NHPs) [9,13]. They all have similarities to human physiology and anatomy, which makes them suitable for preclinical studies.…”

Section: Large Animal Modelsmentioning

confidence: 99%

“…Compared to small animal models, large animals provide a more clinically relevant model to test the translatability of new therapies [9,13].…”

Section: Large Animal Modelsmentioning

confidence: 99%

“…In contrast, pig and dog models are a satisfactory solution offering a relative ease of experimental handling, lower costs of breeding and handling, and in terms of pigs, they are socially more accepted [9]. However, the choices of available species-specific immunoreagents are still limited, but the increased demand is leading to the development of new reagents [9].…”

Section: Large Animal Modelsmentioning

confidence: 99%

“…However, finding the right animal model can be challenging: small animal models require specifically skilled personnel with specialized microsurgery abilities, which is often not available. In addition to the ethical concerns and regulatory burdens, large animal studies are extremely labor-intensive and expensive [7,9].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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