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Graft-versus-host disease (GVHD) remains a frequent complication of hematopoietic cell transplantation (HCT) with skin being a principal target organ. Murine models have provided some insight into the mechanisms of this complex disease process. However, mouse skin differs from human skin, and results of studies in rodents may not translate well to the clinic. The pig is a well-recognized animal model for preclinical studies of skin including dermal toxicology, transdermal drug delivery and wound healing. Unlike skin of rodents, dogs or non-human primates, porcine skin is similar to human skin in terms of structure of epidermal rete ridges, hair follicle structure and density, and presence of sweat glands and subcutaneous fat. Because of the similarities of pig skin to human skin and availability of swine with defined MHC genes, MGH miniature swine provide a valuable pre-clinical model of HCT for studies of graft-versus-host disease. HCT between MHC matched or mismatched animals can be performed to mimic clinical HCT scenarios with outcomes that closely resemble those observed in human HCT recipients. With myeloablative conditioning, HCT across MHC barriers is most often fatal, with animals developing severe grade III-IV GVHD involving the gastrointestinal tract (GI), liver and skin. We have developed a comprehensive GVHD scoring system for pigs which parallels that used clinically (see chart). Unlike rodent models, miniature swine provide an opportunity to perform extended longitudinal studies, since multiple tissue biopsies can be taken without the need to sacrifice the animal. Given the similarities of GVHD in pigs and humans, we hope that the utilization of the pig and scoring system facilitates scientific discourse between the laboratory and the clinic. We anticipate that results of swine studies will be applicable to the development of new strategies to improve GVHD identification and treatment in clinical HCT scenarios.
