Pre-clinical research into allogeneic tissue transplantation therapies, as well as patient-specific regenerative medicine studies, require animal models that closely mimic the typical patient's immune response. Humanized mouse models offer a tractable in vivo system to experimentally test immunological hypothesizes and therapeutic interventions in the context of a human immune system. In the work presented here, we explore the development of a novel humanized mouse model incorporating non-fetal tissue sources: cryopreserved human pediatric thymus tissue and umbilical cord blood hematopoietic stem cells. This model is equivalent to commonly used human fetal tissue models, such as the “BLT” mouse, with regard to frequency of human cell engraftment and distribution and function of various lymphocyte subsets relevant to transplant tolerance and rejection. Further, there are several benefits of this model over fetal tissue-based models. These benefits are associated with the sheer abundance of pediatric tissue available for mouse creation relative to fetal tissue, which allows for in-depth examination of a variety of parameters that are not feasible with limited quantities of fetal specimens. Additionally and not insignificantly, this non-fetal tissue based model side-steps the ethical barriers associated with conducting fetal tissue research in our current political environment. Finally, the more developmentally mature tissues used in our model may afford a more accurate representation of clinical patient immune responses in terms of T cell gene expression patterns and function.

CITATION INFORMATION: Brown M, Norman I, Zhou Y, Lou W, Sullivan J, Burlingham W. A Novel Humanized Mouse Model Incorporating Non-Fetal Tissue. Am J Transplant. 2016;16 (suppl 3).

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