Hamaoui Karim, Gowers Sally, Sandhu Bynvant, Vallant Natalie, Cook Terry, Boutelle Martyn, Casanova Daniel, Papalois Vassilios
Department of Surgery, Imperial College London, London, UK.
Department of Bioengineering, Imperial College London, London, UK.
J Surg Res. 2018 Mar;223:263-274. doi: 10.1016/j.jss.2017.11.052. Epub 2018 Jan 8.
Hypothermic machine perfusion (HMP) is increasingly being used for extended criteria kidney grafts. Pancreatic HMP is challenging because physiologically the pancreas is a low-flow organ susceptible to edema. We report the successful development of preclinical HMP models using porcine pancreases, as well as human pancreases unsuitable for clinical transplantation.
Ten porcine pancreases were used in the development of these perfusion models. Pancreases underwent 24 h of static cold storage (SCS, n = 3) and then viability assessment on an isolated oxygenated normothermic reperfusion (NRP) circuit or 24-h SCS, 5 h of HMP, and then NRP (SCS-HMP, n = 3). Human pancreases (n = 3) were used in the development of a preclinical model.
Porcine HMP demonstrated stable perfusion indices at low pressures, with a weight gain of between 15.3% and 27.6%. During NRP, SCS-HMP pancreases demonstrated stable perfusion flow indices (PFIs) throughout reperfusion (area under the curve was in the range of 0.49-2.04 mL/min/100 g/mm Hg), whereas SCS-only pancreases had deteriorating PFI with a decline of between 19% and 46%. Human pancreas models demonstrated stable PFI between 0.18 and 0.69 mL/min/100 g/mm Hg during HMP with weight gain of between 3.9% and 14.7%. NRP perfusion in porcine and human models was stable, and functional assessment via insulin secretion demonstrated beta cell viability. Exocrine function was intact with production of pancreatic secretions only in human grafts.
Application of machine perfusion in preclinical porcine and human pancreas models is feasible and successful; the development of these translational models could be beneficial in improving pancreas preservation before transplantation and allowing organ viability assessment and optimization.
低温机器灌注（HMP）越来越多地用于扩大标准的肾移植。胰腺HMP具有挑战性，因为从生理角度来看，胰腺是一个低流量器官，易发生水肿。我们报告了使用猪胰腺以及不适用于临床移植的人类胰腺成功开发临床前HMP模型的情况。
在这些灌注模型的开发中使用了10个猪胰腺。胰腺经历24小时静态冷藏（SCS，n = 3），然后在孤立的含氧常温再灌注（NRP）回路上进行活力评估，或者24小时SCS、5小时HMP，然后进行NRP（SCS - HMP，n = 3）。人类胰腺（n = 3）用于临床前模型的开发。
猪HMP在低压下显示出稳定的灌注指标，重量增加在15.3%至27.6%之间。在NRP期间，SCS - HMP胰腺在整个再灌注过程中显示出稳定的灌注流量指标（PFIs）（曲线下面积在0.49 - 2.04 mL/min/100 g/mm Hg范围内），而仅SCS的胰腺PFIs恶化，下降幅度在19%至46%之间。人类胰腺模型在HMP期间显示出稳定的PFI，范围在0.18至0.69 mL/min/100 g/mm Hg之间，重量增加在3.9%至14.7%之间。猪和人类模型中的NRP灌注稳定，通过胰岛素分泌进行的功能评估显示β细胞活力。外分泌功能完好，仅在人类移植物中产生胰腺分泌物。
在临床前猪和人类胰腺模型中应用机器灌注是可行且成功的；这些转化模型的开发可能有助于改善移植前胰腺的保存，并允许进行器官活力评估和优化。
