The Microsurgery Core will provide expertise and quality control over animal transplantation models forProjects by Tellides, Pober, Min, and Bender of the program. The core unit will serve as a central resource to utilize the human artery transplantation models in immunodeficient mouse chimeras that have been developed at YaleUniversity. Double-mutant severe combined immunodeficient (SCID)/beige mice are grafted with human orsynthetic arteries and are subsequently immunologically reconstituted with an adoptive transfer of humanleukocytes and/or are treated with human cytokines, such as the species-specific Th1 factor, interferon-gamma(IFN-y). The interactions of the leukocytes or cytokines with the graft vascular cells results in immunemediatedarterial injury in a surrogate human experimental model. Additionally, various mouse recipientstrains are grafted with mouse aorta segments to take advantage of the power of murine genetic models tosupplement the human tissue data. The Microsurgery Core will also develop and adapt the artery graftmodels according to Project requirements, e.g. developing a Rag1 mutant rat recipient to study remodelingin larger primary branches of human epicardial coronary arteries. All four projects will be supported by theMicrosurgery Core.
The aims of the Microsurgery Core are:1) to provide the complex small animaltransplantation models to the Program investigators; 2) to develop new methods for improving or adaptingthe in vivo models; and 3) to provide a microsurgery training resource for investigators in vascular andtransplantation biology. The methodology of the human artery-SCID/beige mouse transplantation model isrelatively complex and requires shared facilities and special skills. The Microsurgery Core personnel haveextensive experience with the required techniques and their combined expertise is essential to ensureconsistency of the models and an economy of scale. By providing the artery graft models to all of theprojects, the Microsurgery Core will play a key role in this program.
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