Hypothermic machine perfusion in uterus transplantation in a porcine model: A proof of concept and the first results in graft preservation

IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY
Carla Héléna Sousa, Marion Mercier, Nathalie Rioux-Leclercq, Erwan Flecher, Claude Bendavid, David Val-Laillet, Juliette Ferrant, Sylvie Jaillard, Emma Loiseau, Julien Branchereau, Yanis Berkane, Krystel Nyangoh Timoh, Isis Carton, Maëla Le Lous, Vincent Lavoue, Ludivine Dion
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Abstract

Introduction

Graft optimization is a necessity in order to develop uterus transplantation from brain-dead donors, as a complement to living donors, as these grafts are rare and the last organs retrieved in multiple organ donation. The aim of this study was to assess the feasibility and interest of hypothermic machine perfusion (HMP) in uterus transplantation using a porcine model; secondary outcomes were the evaluation of the graft's tolerance to a prolonged cold ischaemia time and to find new biomarkers of uterus viability.

Material and Methods

Fifteen uterus allotransplantations were performed in a porcine model, after 18 h of cold ischaemia, divided in three groups: Static cold storage in a HTK solution, HMP (with the VitaSmart (™) machine Bridge to Life Ltd.) with a UW-MP solution, and static cold storage in a UW solution. The main outcome was macroscopic: uterine arteries pulsatility, recoloration, and bleeding at the cut. Secondary outcomes were histological analyses (Zitkute and inflammation scores), caspase3 immunohistochemistry and plasmatic dosage of biomarkers.

Results

14/15 allotransplantations were performed according to the protocol and met the criteria of macroscopic vitality. Grafts treated with HMP (MP did not show significantly more tissue) damage than the recipient's uterus, contrary to grafts in static cold storage, independently of the solution used. This difference disappeared one and 3 h after uterus transplantation. Plasma dosages before and after uterus transplantation did not allow to identify a new biomarker of uterus viability.

Conclusions

HMP is feasible in a porcine model, without inflicting damage on the grafts during cold ischaemia time. Grafts exposed to HMP seemed to better endure reperfusion phenomena, but this advantage did not last over time.

Abstract Image

低温机器灌注在猪模型子宫移植:概念的证明和移植保存的第一个结果。
为了发展脑死亡供者的子宫移植,作为活体供者的补充,移植物优化是必要的,因为这些移植物是罕见的,并且是多器官捐赠中最后获得的器官。本研究的目的是评估低温机器灌注(HMP)在猪模型子宫移植中的可行性和价值;次要结果是评估移植物对长时间冷缺血的耐受性,并找到子宫活力的新生物标志物。材料和方法:在猪模型中进行15例同种异体子宫移植,在冷缺血18小时后,分为三组:HTK溶液中静态冷藏,UW- mp溶液中HMP(使用VitaSmart(™)机器Bridge to Life Ltd.), UW溶液中静态冷藏。主要结果是肉眼可见的:子宫动脉搏动,重新着色,切口出血。次要结果是组织学分析(Zitkute和炎症评分)、caspase3免疫组织化学和生物标志物的血浆剂量。结果:14/15例异体移植手术均按方案进行,符合宏观活力标准。用HMP处理的移植物(MP没有显示出明显更多的组织)比受体子宫损伤,与静态冷藏的移植物相反,与使用的溶液无关。这种差异在子宫移植后1 h和3 h消失。子宫移植前后血浆剂量不能确定子宫活力的新生物标志物。结论:HMP在猪模型上是可行的,在冷缺血期间不会对移植物造成损伤。暴露于HMP的移植物似乎能更好地忍受再灌注现象,但这种优势并没有持续一段时间。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.00
自引率
4.70%
发文量
180
审稿时长
3-6 weeks
期刊介绍: Published monthly, Acta Obstetricia et Gynecologica Scandinavica is an international journal dedicated to providing the very latest information on the results of both clinical, basic and translational research work related to all aspects of women’s health from around the globe. The journal regularly publishes commentaries, reviews, and original articles on a wide variety of topics including: gynecology, pregnancy, birth, female urology, gynecologic oncology, fertility and reproductive biology.
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