Sprague Dawley to Wistar, a novel combination to perform heterotopic small bowel transplantation model in rats and to study the acute cellular rejection process

PABLO STRINGA; NATALIA LAUSADA; SABRINA GAMBARO; CABANNE, ANA; GONDOLESI GABRIEL; MARTIN RUMBO

Mar del Plata

Congreso; LXII Reunión de la Sociedad Argentina de Inmunología.; 2014

Graft rejection (GR) is a major clinical complication in intestinal transplant. Experimental models are essential to better understand GR and establish preventive strategies. Our aim was to optimize a model of heterotopic intestinal transplantation (HIT) in rats to evaluate GR. Four syngeneic HIT (Wistar as donor and recipient) and 4 allogeneic HIT (Sprague Dawley as donor, Wistar as recipient) were performed. Clinical parameters (signs of pain, distress and weight loss) and intestinal graft (ostomy appearance and tightening compatible with GR) were evaluated daily. Animals showing signs of discomfort or tightening of the graft were sacrificed. Graft was sampled at 30 min, 3, 5, 7 days after HIT and at sacrificed for histological analysis. Rejection was diagnosed by the presence of inflammatory cell infiltrate and increased apoptosis/10 intestinal crypts. Syngeneic grafts showed no histologic changes compatible with GR. Ischemia-reperfusion damage (Parks index > 3) was evident at 30 min post HIT. Recipients survived healthy up to 6 months after HIT without grafts abnormalities. Allogeneic recipients showed alterations compared with syngeneic group. Weight loss and graft tightening at 5 (1/4), 7 (2/3) and 9 (1/1) pos-HIT days were diagnosed. Significant differences in graft survival between groups were observed (p< 0.001, Log-rank test). Increase in apoptotic cells was observed from pos-HIT day 3. Focal lesions compatible with acute cellular GR were present since day 5. However, inflammatory cell infiltrate was not as evident compared to the degree of mucosal changes. Perivascular inflitrate in mesenteric vessels and mucosal epithelial lesions compatible with ischemic damage were observed in the final stages precedent to endpoint. Although Sprague Dawley-Wistar combination has not been used so far in HIT models, results showed here are coincident with other combinations reported in the literature. The optimized model is useful to study immunobiology of intestinal GR