Abstract
Introduction: Abdominal wall, the second mostly performed allotransplanted composite tissue, is less studied and lacking appropriate animal models. Its clinical necessities were emphasized in multiple case series to reconstruct large abdominal defects. The technical success is shadowed by problematic immunological and functional outcomes. We aim to establish a reproducible and cost-effective model to study the various treatment regimens, immune profile, and natural history of this specific allotransplant. Methods: Full thickness hemi-abdominal wall flap including the peritoneum is procured from Brown Norway (BN) rats and transplanted to an orthotopic defect on Lewis rats. Five groups were studied:Group 1: Lewis to Lewis syngeneicGroup 2: BN to Lewis controlGroup 3: BN to Lewis with 30 days CyclosporineGroup 4: BN to Lewis with 30 days Cyclosporine plus 4 doses of recipient adipose-derived stem cells (ADSC) intravenouslyGroup 5: BN to Lewis with 30 days Cyclosporine plus 4 doses of recipient ADSC subcutaneouslyGroup 3 to 5 also received one dose of anti-lymphocyte globulin on the day prior to surgery. Vascular imaging and cross sectional vessel biopsy were performed at the time of surgery and on day 60 along with full thickness abdominal wall biopsy. Immune cell profiling with flow cytometry at different time points was studied in all groups. Rejection is defined when de-epithelialization is first observed. Results: The rat abdominal model has near 100% surgical success rate. Syngeneic group showed no rejection. Control group consistently showed rejection on postoperative day 7. However, with cyclosporine treatment, rejection is delayed to day 50. ADSC plus cyclosporine currently showed even longer rejection-free period. No observable difference is yet seen between subcutaneous and intravenous ADSC groups. Interim cytometry results at time of rejection in control group indicated that Th1 cells mediate the rejection of abdominal wall transplant, whereas Th2 cells or IL-10-producing T cells down-regulate the rejection progression. Conclusion: We first developed a reproducible abdominal wall allotransplantation model in rats. Through this new model, we studied different immune modulation regimens, natural history, and immune profile of the allograft.Figure: [HAW]
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