title: Multiple human mesenteric arterial grafts from the same donor to study human chronic vascular rejection in humanized SCID/beige mice.
abstract: 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.
authors.affiliation: INSERM U466, University Hospital Rangeuil, Toulouse, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Marcheix
authors.forename: Houda
authors.initials: H
authors.lastname: Yacoub-Youssef
authors.forename: Denis
authors.initials: D
authors.lastname: Calise
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Thiers
authors.forename: Nicole
authors.initials: N
authors.lastname: Therville
authors.forename: Hervé
authors.initials: H
authors.lastname: Benoist
authors.forename: Nelly
authors.initials: N
authors.lastname: Blaes
authors.forename: Bruno
authors.initials: B
authors.lastname: Ségui
authors.forename: Xavier
authors.initials: X
authors.lastname: Game
authors.forename: Camille
authors.initials: C
authors.lastname: Dambrin
authors.forename: Mogens
authors.initials: M
authors.lastname: Thomsen
mesh_terms: 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