Use of human mesenteric arteries to study chronic vascular rejection in SCID/beige mice reconstituted with human spleen cells

Abstract

We wanted to establish a preclinical model of chronic vascular rejection (CVR) by transplanting small arteries from the mesentery of cadaveric organ donors by the rapid “sleeve” technique into SCID/beige mice reconstituted with human allogeneic spleen cells. After institutional authorization and with informed consent from relatives, we obtained tissues and cells from cadaveric organ donors. A piece of mesentery was recovered from the donor and kept in buffered solution at 4°C until use. After dissection of the mesentery, small arteries of suitable size were transplanted in place of the infrarenal aorta of the mice. Cells for the immunological reconstitution of the mice were spleen cells from the same or other organ donors. Twenty-three suitable arterial segments were obtained from the mesentery of three cadaveric donors. Ten of the mice received 3 × 10 7 human spleen cells intraperitoneally 1 week after the arterial graft and they all showed circulating human CD3+ and CD19+ cells 2 weeks after injection. The mice were sacrificed 5 weeks after the arterial graft. SCID/beige mice reconstituted with allogeneic spleen cells showed a typical CVR, whereas mice that received no cells had a normal vascular anatomy. We believe our model is well suited for the study of treatment of CVR under human allograft conditions.