title: Preclinical modeling of hematopoietic stem cell transplantation - advantages and limitations.
abstract: Hematopoietic stem cell transplantation, which was first successfully performed in the 1950s, remains a critical therapeutic modality for treatment of a diverse array of diseases, including a multitude of hematological malignancies, autoimmune disorders, amyloidosis and inherited genetic hematological disorders. Although great advances have been made in understanding and application of this therapy, significant complications still exist, warranting further investigation. Of critical importance, graft-versus-host disease (GVHD), in both acute and chronic forms, remains a major complication of hematopoietic stem cell transplantation, responsible for both the development of chronic illness and morbidity, as well as mortality. Use of an appropriate preclinical model may provide significant insight into the mechanistic pathways leading to the development and progression of graft-versus-host disease, as well as cancer in general. However, existing preclinical modeling systems exhibit significant limitations, and development of models that recapitulate the complex and comprehensive clinical scenario and provide a tool by which therapeutic intervention may be developed and assessed is of utmost importance. Here, we review the present status of the field of graft-versus-host disease research. We discuss and summarize the preclinical models currently in use, as well as their advantages and limitations.
authors.affiliation: Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Stolfi
authors.affiliation: Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA, USA.
authors.forename: Chien-Chun S
authors.initials: CC
authors.lastname: Pai
authors.affiliation: Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA, USA.|Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Murphy
mesh_terms: D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy; D002908:Chronic Disease; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D011323:Primates; D051381:Rats; D013045:Species Specificity
keywords: adoptive therapy; cancer; canine; conditioning; graft versus tumor; graft versus-host disease; hematopoietic stem cell transplantation; immunotherapy; preclinical; primate