Multiple human mesenteric arterial grafts from the same donor to study human chronic vascular rejection in humanized SCID/beige mice.
BACKGROUND
Chronic vascular rejection (CVR) is a major problem in clinical transplantation. Studies in experimental animals have been important to understand some of its mechanisms, but they are hampered by the difficulty of extrapolating the results into clinical practice.


METHODS
We created a new experimental model for the study of human CVR by grafting multiple human mesenteric arteries from the same human donor into different SCID/beige mice in the infrarenal aortic position. Twenty-seven different mice were successfully grafted with a human artery from 6 donors. One week later, 23 of the mice received an intraperitoneal injection of 40 million human spleen cells, either from the same donor (autologous) or from another donor (allogeneic).


RESULTS
In 81% of the mice an immune reconstitution was obtained, shown by the presence of human T, B and NK cells and IgG in circulating blood. At the time of sacrifice, 5 weeks after the arterial transplantation, a typical CVR with infiltration of human immune cells and deposit of human immunoglobulin was observed in the reconstituted mice that received allogeneic cells, whereas only minor lesions were noted in autologous combinations. No CVR was observed without injection of human splenocytes. We did not observe lymphoma or graft-vs-host reactions during the experiment.


CONCLUSIONS
We show that it is feasible to graft multiple human arteries from the same donor into SCID/beige mice, and that a specific and typical CVR is observed after reconstitution with allogeneic spleen cells. Our method allows for pre-clinical testing of new therapeutics in controlled series.
Marcheix
Bertrand
B
INSERM U466, University Hospital Rangeuil, Toulouse, France.
Yacoub-Youssef
Houda
H
Calise
Denis
D
Thiers
Jean-Claude
JC
Therville
Nicole
N
Benoist
Hervé
H
Blaes
Nelly
N
Ségui
Bruno
B
Game
Xavier
X
Dambrin
Camille
C
Thomsen
Mogens
M
D000714:Anastomosis, Surgical; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008638:Mesenteric Arteries / Q000637:transplantation*; D051379:Mice; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology*; D013536:Suture Techniques; D014183:Transplantation, Heterologous; D017539:Tunica Intima / Q000473:pathology