Because of the severe shortage of available human organs for donations, other species have been considered as potential donors for human transplantation. Of the options available the pig appears to be the most suitable candidates. Hyperacute rejections has been a major barrier to pig-to-human transplantation, although several strategies have been successful in preventing this. Despite preventing hyperacute rejection, delayed xenografic rejection occurs which is characterized by endothelial cell activation and invasion of macrophages and natural killer cells. Although many of the successful strategies to avert hyperacute rejection have used approaches which prevent complete activation of the complement cascade, none have attempted to inhibit the complement cascade in its earliest phases. Deposition of the initial components of the complement cascade (c1, c4, c2) can lead to the accumulation of inflammatory cells and may contribute to endothelial cell activation thus creating a situation which is consistent with delayed xenograft rejection. Using novel synthetic peptides (complementary binding peptides) developed at Northwestern University, we will attempt to block the deposition of the early components of the complement cascade, thus preventing hyperacute rejection as well as the pro-inflammatory stimulus which is elicited from these early components. This will be tested in an ex vivo perfusion circuit where human blood is perfused through a pig heart with and without the complementary binding peptides.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
2M01RR000048-36A1
Application #
6245181
Study Section
Project Start
1997-07-15
Project End
1997-11-30
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
36
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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