Work

34. Ex Vivo Machine Perfusion Of Vascularized Composite Allotransplants Reduces Inflammatory Response In Rodents

Year: 2024

Type: article

Abstract: Purpose: Vascularized Composite Allotransplantation (VCA) has 90% incidence of acute rejection in the first year. It remains unclear how graft preservation impacts rejection. This study compared simple cold storage and ex vivo machine perfusion - a promising tool to improve, modify, and preserve grafts - on tissue rejection responses in a rat allotransplant model. Methods: Hindlimbs of male Brown Norway rats are perfused with modified Steen at 37°C for 6h (n = 5). In two control groups, hindlimbs are transplanted directly (warm ischemic time (WIT) < 2h, n = 2) or SCS for 6h (n = 5). After foot removal, partial hindlimbs are transplanted to male Lewis rat recipients. Animals are observed for 7 days. Tail vein blood is drawn on days 0, 1, 3, and 7 and analyzed with Multiplex immunoassay for inflammatory cytokines and chemokines. Signs of clinical rejection are assessed and scored by blinded surgeons. Results: Perfused hindlimbs show improved parameters (potassium, lactate, resistance) at end of perfusion, stable metabolic parameters (glucose and oxygen consumption), and acceptable weight gain. Surgical WIT was comparable between groups. Clinical graft observation showed no significant difference. Postoperatively, pro-inflammatory cytokines IL-1a, IL-17a, IL-18 and IFN-γ were higher in SCS group compared to perfused and direct groups, especially on POD 7. Perfused group also exhibited increasing levels of anti-inflammatory cytokine IL-10 over time. RANTES, a chemokine that mediates monocyte/macrophage infiltration, was higher in SCS group as well. Conclusion: This study shows reduced acute rejection response in vivo of machine perfused hindlimbs compared to 6h of SCS and direct transplantation at day 7. Herein, we demonstrate the foundation for the development of machine perfusion in the VCA field, to serve as a platform to reduce rejection and open possibilities for graft modification and extending preservation.

Source: Plastic & Reconstructive Surgery Global Open

DOI: 10.1097/01.gox.0001015228.71937.e0