The Microsurgery Core will provide expertise and quality control over animal transplantation models for Projects 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 Yale University. Double-mutant severe combined immunodeficient (SCID)/beige mice are grafted with human or synthetic arteries and are subsequently immunologically reconstituted with an adoptive transfer of human leukocytes 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 immunemediated arterial injury in a surrogate human experimental model. Additionally, various mouse recipient strains are grafted with mouse aorta segments to take advantage of the power of murine genetic models to supplement the human tissue data. The Microsurgery Core will also develop and adapt the artery graft models according to Project requirements, e.g. developing a Rag1 mutant rat recipient to study remodeling in larger primary branches of human epicardial coronary arteries. All four projects will be supported by the Microsurgery Core.
The aims of the Microsurgery Core are:1) to provide the complex small animal transplantation models to the Program investigators;2) to develop new methods for improving or adapting the in vivo models;and 3) to provide a microsurgery training resource for investigators in vascular and transplantation biology. The methodology of the human artery-SCID/beige mouse transplantation model is relatively complex and requires shared facilities and special skills. The Microsurgery Core personnel have extensive experience with the required techniques and their combined expertise is essential to ensure consistency of the models and an economy of scale. By providing the artery graft models to all of the projects, the Microsurgery Core will play a key role in this program.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL070295-10
Application #
8117194
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
10
Fiscal Year
2010
Total Cost
$221,726
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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