Heterotopic Small Bowel Transplantation Model in Rats: Sprague Dawley to Wistar, a Novel Donor-Recipient Combination to Study the Acute Cellular Rejection Process.

PABLO STRINGA; NATALIA LAUSADA; SABRINA GAMBARO; JUAN CRUZ ABATE; ANA CABANNE; CLEMENTE RAIMONDI ; GABRIEL E. GONDOLESI ; MARTIN RUMBO

Simposio; International Small Bowel Transplant Symposium 2015; 2015

Intestinal Transplant Association

Graft rejection (GR) is a major clinical complication in intestinal transplant.Experimental models are essential to better understand GRand establish preventive strategies and improve diagnosis.Our aim was to optimize a model of heterotopic intestinal transplantation(HIT) in rats to evaluate in detail the progression of acute celluelarrejection.Five syngeneic HIT (Wistar as donor and recipient) and 7 allogeneicHIT (Sprague Dawley as donor, Wistar as recipient) were performed.Clinical parameters (signs of pain, distress and weight loss) and intestinalgraft (ostomy appearance and tightening compatible withGR) were evaluated daily. Animals showing signs of discomfort ortightening of the graft were sacrificed.Graft was sampled at 30 min, 3, 5, 7 days after HIT and at sacrificefor histological analysis. Rejection was diagnosed by the presenceof inflammatory cell infiltrate and increased apoptosis/10 intestinalcrypts.Syngeneic grafts showed no histologic changes compatible with GR.Ischemia-reperfusion injury (Parks index >3) was evident at 30 minpost HIT. Recipients survived healthy up to 6 months after HIT withoutgrafts abnormalities.Allogeneic recipients showed alterations compared with syngeneicgroup. Weight loss, graft tightening at 5 (1/7), 7 (3/6), 9 (1/3) and 12(2/2) pos-HIT days and others clinical alterations were diagnosed.Significant differences in graft survival between groups were observed(p< 0.001, Log-rank test). Increase in apoptotic cells was observedfrom pos-HIT day 3. Focal lesions compatible with acutecellular GR were present since day 5. Significant cellular infiltrateand severe epithelial damage compatible with exfoliative GR wereobserved in samples taken at 12 post-HIT day.Perivascular inflitrate in mesenteric vessels and muscular and serosalayers were also evident along rejection progression. In some cases,cellular infiltrate in muscular and serosal layers was evident at earliertime points than mucosal epithelial lesions.HIT using Wistar as donor and Sprague Dawley as recipient werealso perfomed. Histological and clinical observations indicated thatGR process was similar to the mentioned above.Although Sprague Dawley-Wistar combination has not been used sofar in HIT models, results showed here are coincident with otherstrains combinations reported in the literature. The optimized modelis useful to study in detail the immunobiology of intestinal GR.References:1. Intestinal transplantation outcomes.2. Intestinal transplant. Review and description of its evolution inLatin America.