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Biocontainment facilities and positive pressure isolators are developed to limit pathogen exposure and prolong the life of SCID pigs. Raising SCID pigs in such facilities allows for completion of long-term studies such as xenotransplantation of human cells. Ectopically injected human cancer cell lines develop into tumors in SCID pigs, thus providing a human-sized in vivo model for evaluating imaging methods to improve cancer detection and therapeutic research and development.
Immunocompromised pigs have the potential to be immunologically humanized by xenotransplantation with human hematopoietic stem cells, peripheral blood leukocytes, or fetal tissue. These cells can be introduced through various routes including injection into fetal liver or the intraperitoneal IP space, or into piglets by intravenous, IP, and intraosseous administration.
The development and maintenance of transplanted human immune cells would be initially at least dependent on immune signaling from swine cells. Compared to mice, swine share higher homology in immune related genes with humans.
We hypothesize that the SCID pig may be able to support improved engraftment and differentiation of a wide range of human immune cells as compared to equivalent mouse models. Humanization of SCID pigs would thus provide a valuable model system for researchers to study interactions between human tumor and human immune cells.
Additionally, as the SCID pig model is further developed, it may be possible to develop patient-derived xenograft models for individualized therapy and drug testing. We thus theorize that the individualized therapeutic approach would be significantly improved with a humanized SCID pig due to similarities in size, metabolism, and physiology. In all, porcine SCID models have significant potential as an excellent preclinical animal model for therapeutic testing.
Keywords: severe combined immunodeficiency, swine, humanization, cancer, xenograft, pre-clinical, animal model Introduction A new field of personalized medicine has been evolving over the last decade, especially with respect to advances in individualized cancer therapies, ranging from T cell and NK cell immunotherapies, targeted monoclonal antibody therapy, and newly developed small molecule drugs.
As progress is made toward the development of cancer therapies, it is critical that preclinical animal models can dependably represent human responses to drugs.
Presently, mice are the most commonly used model for preclinical animal drug trials 1. However, many preclinical cancer drug trials that succeed in mice fail in humans due to vast differences in physiology, metabolic processes, and size 2 , 3.
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