Dominic Richard Beal
Biomodels, LLC, 313 Pleasant Street, Watertown, MA 02472, USA
Graft-versus-host disease (GVHD) is a major source or morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Despite advances in understanding of the immuno-pathological basis of GVHD there is currently no standardized effective treatment available. The focus of current therapy is general immune suppression, which has dubious efficacy; sustained amelioration of disease symptoms is only seen in around 50% of patients. More promising therapies are based on the prevention of development of GVHD, and use more specifically T cell targeting agents such as tacrolimus, and novel JAK signaling pathway inhibitors.
Here we describe three murine models of GVHD – acute, chronic sclerodermatous, and human xenograft – which address many of the aspects of the human disease. Enhancements to these models such as direct measurement of intestinal inflammation by serial, in-life video endoscopy, and assessment of engraftment by flow cytometry, add to the efficiency and reliability of these models by providing the investigator with tools to more effectively randomize treatment groups, predict disease severity, and verify mechanisms of action for novel therapeutics.
Moreover, recent discoveries in the role of the microbiome and its effects on multiple disease states have demonstrated a pressing need for further research. Here we present data showing that manipulations of and/or vendor specific differences in the intestinal microbiota can influence the kinetics and severity of GVHD, and therefore must be taken account of in the design of studies as well as interpretation of results.
Keywords: Graft versus Host, GVHD, murine model, microbiome.