Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion
Year: 2025
Type: article
Abstract: Background: Subnormothermic machine perfusion shows promise as a viable alternative to static cold storage for prolonged preservation of vascularized composite allografts. To date, most studies have been conducted in nonprimate models, and we report its first utilization in a cynomolgus forearm preclinical model for 24-h preservation. Methods: Forearms were procured from nonhuman primates weighing between 5 and 8 kg. Two perfusion protocols were implemented. In group 1 (n = 6), limbs were perfused with 1.5 L of recirculating Steen; the perfusate flow was adjusted to maintain stable vascular pressures. In group 2 (n = 6), limbs were perfused with a Steen+ solution, doubling the albumin concentration, with a full-volume exchange at mid-perfusion under a stable low-flow regimen. Dynamic and metabolic parameters, histological analysis, and response to neurostimulation were assessed. Results: After 24 h of continuous perfusion, mean weight gain was 24.8 ± 5.5% in group 1 and 8.0 ± 4.7% in group 2. Perfusion and metabolic parameters indicated the onset of a compartment syndrome in group 1 with an increase in resistance, lactate, and potassium production at mid-perfusion. In group 2, dynamic and metabolic parameters remained stable for 24 h, and histological analysis showed well-preserved tissues. Finally, in group 2, limbs exhibited muscular contraction recovery quantified at 2.4/5 ± 0.89 after 24 h compared with 0/5 after 3 h of ischemia or after perfusion in group 1. Conclusions: Successful 24-h perfusion and muscle contractility restoration demonstrate promising outcomes for vascularized composite allograft preservation and reconditioning.
Source: Transplantation Direct
Institutions: Harvard University, Massachusetts General Hospital, Hôpital de la Croix-Rousse, Shriners Hospitals for Children - Boston, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Régional et Universitaire de Nancy, Inserm, Université Paris Cité, Innovations Thérapeutiques en Hémostase
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
OpenAlex ID: W4413100606
