Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion

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 prec...

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Main Authors: Haïzam Oubari, MD, Loïc Van Dieren, MS, Yanis Berkane, MD, Lucile Cabanel, MD, Mark A. Randolph, MAS, Curtis L. Cetrulo, Jr, MD, Alexandre G. Lellouch, MD, Korkut Uygun, PhD
Format: Article
Language:English
Published: Wolters Kluwer 2025-09-01
Series:Transplantation Direct
Online Access:http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001849
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Summary: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.
ISSN:2373-8731