Animal models of chronic graft-versus-host disease with oral involvement: A review

Chronic graft-versus-host disease (cGVHD) remains a significant complication following allogeneic hematopoietic stem cell transplantation, with the oral cavity being one of the most frequently affected sites. Oral cGVHD manifests mucosal inflammation, salivary gland dysfunction, and fibrosis, all of which substantially impair patients' quality of life. To date, research efforts have predominantly focused on clinical investigations, with relatively limited exploration of animal models for in vivo studies, despite animal models playing a pivotal role in deciphering the pathobiology of cGVHD and developing therapeutic strategies. This review synthesizes the classification, modeling methodologies, and pathological characteristics of systemic GVHD animal models, with particular emphasis on the phenotypic manifestations of oral involvement. By critically assessing the strengths and limitations of murine, rat, canine, and nonhuman primate models, this article aims to provide a comprehensive narrative framework for selecting appropriate animal models in future in vivo studies of oral cGVHD.