Cellular basis of transplant arteriosclerosis in mice
AssigneePresident and Fellows of Harvard College
InventorsEdgar Haber, Chengwei Shi, Wen-Sen Lee
Life of this patent
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Abstract
A mouse model for transplant arteriosclerosis useful for identifying compounds which reduce or prevent such arteriosclerosis, consisting of a mouse engrafted with a histoincompatible artery which exhibits detectable arteriosclerosis within 30 days of transplantation. Also disclosed are therapeutic methods for inhibiting the development of transplant arteriosclerosis in mammalian recipients of allografted organs.
Claims32
A surgically modified mouse, comprising an artery isolated from a histoincompatible donor mouse, wherein the isolated artery is transplanted in an end-to-side or a side-to-side anastomosis to an endogenous artery of said surgically modified mouse, and wherein said transplanted artery exhibits transplant arteriosclerosis within 30 days of transplantation.
A method for screening a candidate compound to determine whether said candidate compound reduces transplant arteriosclerosis, comprising:
- (a) transplanting into a first mouse of a first inbred strain, an artery isolated from a donor mouse of a second inbred strain which is histoincompatible with said first inbred strain in an end-to-side or a side-to-side anastomosis;
- (b) transplanting into a second mouse of said first inbred strain, an artery isolated from a donor mouse of said second inbred strain in an end-to-side or a side-to-side anastomosis;
- (c) administering to said first inbred strain said candidate compound after transplantation of said artery into said first mouse;
- and
- (d) comparing (1) the degree of arteriosclerosis in said artery of said first mouse which occurs within 30 days after transplantation, with (2) the degree of arteriosclerosis in said artery of said second mouse which occurs within 30 days after transplantation, wherein a lesser degree of arteriosclerosis in said artery of said first mouse is an indication that said candidate compound reduces transplant arteriosclerosis.
A method for screening a candidate compound to determine whether said candidate compound reduces transplant arteriosclerosis, comprising:
- (a) transplanting into a first mouse of a first inbred strain, an artery isolated from a donor mouse of a second inbred strain which is histoincompatible with said first inbred strain in an end-to-side or a side-to-side anastomosis, wherein said artery from said donor mouse has been treated with said candidate compound before transplantation of said artery into said first mouse;
- (b) transplanting into a second mouse of said first inbred strain, an artery isolated from a donor mouse of said second inbred strain in an end-to-side or a side-to-side anastomosis;
- and
- (c) comparing (1) the degree of arteriosclerosis in said artery of said first mouse which occurs within 30 days after transplantation, with (2) the degree of arteriosclerosis in said artery of said second mouse which occurs within 30 days after transplantation, wherein a lesser degree of arteriosclerosis in said artery of said first mouse is an indication that said candidate compound reduces transplant arteriosclerosis.
Dependencies are inferred from the claim text.