推动体外器官灌注技术发展，提高捐献器官利用率及质量

器官移植是目前治疗终末期器官衰竭唯一有效的方法,供器官来源短缺严重阻碍器官移植的发展。提高边缘供者供器官使用率可部分缓解器官来源短缺现状。随着器官保存技术的不断发展,机械灌注逐渐成为提高供器官质量的重要研究方向。机械灌注有望成为优于传统静态冷保存的器官保存技术,可改善体外供器官保存环境并提供供器官质量评估体系,更好地修复边缘供者供器官,提高供器官利用率。本文概述器官保存技术的发展历程、研究进展和未来趋势,通过医工融合,共同推动机械灌注技术发展,提高捐献器官质量及利用率。     

机械灌注技术在器官移植中的应用

本文就机械灌注的发展以及在器官移植中的应用进展进行介绍,指出供器官短缺是目前移植领域面临的主要问题,但是机械灌注技术的出现为器官保存提供了新的视角,尤其在扩大标准供者、高风险供者及心脏死亡器官捐献供者的应用上发挥优势,提高了供器官质量,并在扩大供体池方面体现出巨大的潜能和前景。     

聚乙二醇在器官保存中的应用及作用机制

器官移植是根治终末期器官功能衰竭惟一有效的方法,自20世纪60年代在临床应用以来,移植医学已得到了突飞猛进的发展.然而近年来,器官来源短缺已成为阻碍全球器官移植发展的主要问题.为了扩大供者人群,近年来国内外对于边缘供者的利用明显增加,这对传统的器官保存提出了更高的要求.     

HTK液和Celsior液在肝移植中的应用研究

目前 ,UW液是器官移植中常用的多器官保存液 ,同时临床应用经验和前瞻性研究表明 ,HTK液和Celsior液在肝脏移植中的应用安全有效 ,是UW液可靠的替代选择。实验研究发现 ,上述两种保存液可以减轻低温缺血和再灌注损伤 ,改善器官保存效果。本文对近期HTK和Celsior保存液临床应用及实验研究进展作一综述     

器官保存及保存液的研究

正器官移植是治疗各种器官终末期疾病的唯一有效治疗方案。随着器官移植医学的快速发展,尤其是手术技术的进步及新型免疫抑制剂、器官保存方式的应用,器官移植病人的生存率得到显著提高。器官移植也在世界范围内广泛开展。移植等待病人数量不断增加,远远超过器官捐献的数量,器官供应严重不足,而高质量的供体是器官移植成功的先决条件和基本保障[1]。     

尸体供者小肠、肝和肾脏器联合切取及保存技术

目的建立尸体供者全腹腔脏器切取和保存技术,同时为不同的小肠移植、肝移植和肾移植受者提供供器官。方法共进行8次同一尸体供者的全腹腔脏器切取手术。供体切取经腹主动脉与肠系膜下静脉插管,高渗枸橼酸-腺苷肾保存液及UniversityofWisconsin液原位灌注,肝、小肠、胰腺、脾、肾整块切取。供器官经后台修整后,分别成为肝、小肠和肾移植物进行相应的受者移植手术。结果 8次供者腹腔脏器切取和后台修整手术共获取8具小肠移植物、8具肝移植物和16具肾移植物。利用所修整出的供器官成功地完成5次单独小肠移植、8次肝移植和16次肾移植,术后移植物功能良好。结论所建立的尸体供者全腹腔脏器切取和保存技术,可同时为不同的小肠移植、肝移植和肾移植受者提供供器官;借鉴美国匹兹堡大学的供者器官后台分离技术,还可同时为胰腺移植受者提供供器官。     

胰、十二指肠及肾联合获取、修整和保存的实验研究

目的：对供者胰、十二指肠及肾等器官的联合获取、修整和保存方法进行研究。方法：采用原位腹主动脉插管、低温灌注、快速整块切取及体外修整获得可供移植的胰、十二指肠及肾移植物。2例用UW液保存的供胰用于实验研究。结果：获取8例供者的移植物,平均热缺血时间为4min50s,获取时间为18min20s。7例修整成适用于临床作胰、十二指肠及肾的移植物,平均时间为2h。后4次采用UW液灌注和保存的供者器官中,对其中2例供胰进行了保存研究,UW液保存18h的供胰超微结构正常。结论：此方法适合于供者胰、十二指肠及肾的联合获取、修整和保存。     

心死亡供者器官移植历史和现状

世界范围的供者器官极度短缺已经成为制约器官移植发展的主要问题.心死亡供者(DCD)既往又称为无心跳供者,20世纪60年代开始应用于临床.由于移植技术和器官保存技术的提高,DCD在30年后再次引起世界移植界的广泛关注.既往有大量的DCD来源的肾、肝、肺和胰腺移植的成功报道,但对除肾以外的其他器官移植的评价都比较负面.近期一些关于移植物和受者长期随访的数据令人兴奋,值得探讨.本文就DCD来源器官移植的历史和现状作一综述.     

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目的 对供者肝脏等器官的联合获取、修整和保存方法进行研究。方法 采用原位腹主动脉和门静脉插管、低温灌注，快速多器官联合获取、低温保存技术及体外修整获得可供移植的肝移植物。结果 获取122例供者的移植物，平均热缺血时间为4min30s，平均获取时间为20min，平均冷缺血时间为10h。均采用4℃的HCA液(高渗枸橼酸盐腺嘌呤溶液)和UW液灌注和保存。118例修整成适用于临床用的肝的移植物，76例供肝在移植前留取了病理活检标本，病理检查提示供肝结构正常。移植术后，无原发性肝无功能发生。结论 该方法适合于供者肝脏等器官的快速联合获取、修整和保存。     

中国移植器官保护专家共识（2022版）

器官移植是目前治疗终末期脏器功能衰竭最为有效的手段。器官短缺是制约器官移植工作开展的全球性问题 ［1］。供者器官获取、保存及移植后缺血再灌注损伤（ischemic reperfusion injury,IRI）是影响移植预后的重要因素。自20世纪器官移植技术开展以来,器官保护技术一直是该领域的研究热点。器官保...     

Trends in organ preservation

Organ preservation aims to provide a viable graft with primary function post-transplant. The current basis of preservation for transplantation is static cold storage using specific preservation solutions which minimise cellular swelling and membrane pump activity, thus maintaining cellular ATP levels. The current organ shortage and consequent expansion of donor criteria places even greater reliance on minimising graft injury during preservation. This review focuses on current and future advances in preservation technology. The key areas of advance are additives to preservation solutions, alternatives/adjuncts to preservation solutions including perfluorocarbons. A major area of advance is in the modulation of organs during the storage period. This may be achieved by biochemical additives or genetic manipulation. Machine perfusion technology is improving, and this is discussed together with the recent concept of warm (normothermic) perfusion as an alternative means of preservation. The authors provide an overview over the current methods of organ preservation. Cold storage, effective in the short-term is insufficient for marginal organs, does not allow assessment of viability markers, and provokes ischaemic injury. Potential strategies for minimising ischaemic injury include additives to preservation solutions; the two-layer method with perfluorcarbons and UW solution—at present limited to pancreas preservation; organ modulation; organ preconditioning and genetic modification of organs. In particular, the authors illuminate the potential in a reappraisal of the concept of normothermic perfusion.Abbreviations HSP Heat shock proteins - ICAM-1 Intercellular adhesion molecule-1 - I/R Ischaemia reperfusion - PFC Perflurocarbon - UW University of Wisconsin solution     

常温局部灌注在受控心脏死亡肝移植供体中的应用

目前全球器官移植领域所面临的仍是供体短缺的主要问题。由于受体需求量和标准供体的数量的严重不平衡，外科医生们将目光转移到心脏死亡供体（DCD）。相比于脑死亡供体（DBD），DCD面临的主要问题是经历更长的热缺血时间（WIT），以致患者术后并发症发生率增加，尤其是胆道并发症。受控心脏死亡供体（cDCD）是指在符合患者或家属意愿的情况下有计划地退出维持生命的治疗，在一段“无接触”时间后（通常为5 min），宣布患者大脑循环永久缺失，同时快速进行器官恢复。由于使用常规器官保存方法保存的DCD移植物的移植效果不尽如人意，近年来，常温灌注技术所展现出的优势在移植过程中愈发明显，逐渐引起外科医生和科学家们的关注。与活体肝移植以及DBD肝移植不同，DCD在宣布死亡前无法取出移植物。而在常温局部灌注（NRP）中，外科医生们能够在宣布死亡后阻断流向大脑的血液，并通过体外膜氧合启动器官的热灌注，在供体体内恢复供体肝脏的功能，使肝脏产生胆汁并清除乳酸。这一过程为供体肝脏离开供体和移植前的各项指标监测和优化提供宝贵时间。目前已有多项临床研究表明，NRP作为一种原位器官修复技术能够使cDCD供体肝脏的移植效果与DBD供体相近。另外，一些研究者还开发了多种灌注技术的联合应用，包括NRP与机器灌注（MP）以及双低温氧合机灌注（D-HOPE）的联合使用，均展现出良好的移植效果，为肝移植供体保存提供更多可能性。虽然许多学者认为NRP是一种获取更多高质量器官的保存方法，但有研究者质疑该技术的伦理问题。他们认为该技术违背死亡捐赠规则，NRP灌注程序中所涉及的操作可能导致患者的死亡，因此，确保患者的循环以及呼吸的永久性不可恢复状态以及在NRP期间确保脑部循环的缺失尤其重要。鉴于NRP在移植领域的重要性，笔者对NRP技术在cDCD中的应用进行归纳总结。     

Organ retrieval and preservation

The success of organ transplantation can be attributed to many factors but ultimately depends upon retrieval and preservation techniques to maintain the quality of an organ. Thoracic and abdominal organs from deceased donors are retrieved during a multi-organ procedure. The organs are flushed and cooled in-situ with preservation solution followed by dissection and removal. With the high-risk donors such as donation after cardiac death, rapid in-situ cooling is essential to minimize the injury.Live kidney donation is becoming increasingly popular and the disincentives have been significantly reduced by the introduction of minimally invasive techniques such as the laparoscopic retrieval technique. Segments of the liver, pancreas, lung and small bowel are also being used for live donation. Organ preservation relies on hypothermic temperatures to reduce the metabolism and requirement for oxygen. Storing the organ on ice is the most practised method of preservation (static cold storage), although other methods such as hypothermic machine perfusion are becoming popular for kidney preservation. Preservation solutions are designed to maintain cell membrane stability, prevent intracellular acidosis and cellular swelling. Various solutions are available however, the University of Wisconsin (UW) solution remains the gold standard for all organs.This review focuses on retrieval and preservation techniques in solid organ transplantation.     

A new approach in organ preservation: potential role of new polymers

The storage conditions of the donor kidney may influence the deleterious consequences of ischemia/reperfusion (IR), which remains a major source of complications in clinical practice. Delayed graft function (DGF), seen in 20% to 50% of transplanted cadaver kidneys, is a major risk factor affecting early and long-term graft survival, patient management, and costs of transplantation. Cold preservation plays a key role in this process and is based on hypothermia and high potassium solutions. In this review, the authors focused on the major molecular mechanisms of cold storage (CS) injury at the cellular level, which have been recently evidenced with modern biochemical and cell biologic methods. These newly uncovered aspects of cold preservation injury are often not fully addressed by preservation solutions in current clinical practice. The role of new molecules such as polyethylene glycol (PEG) is presented and their properties are analyzed in the organ preservation context. PEG improves organ function recovery and reduces inflammation and fibrosis development in several models. Because organs shortage is also a real public health problem, organs from non-heart beating donors or marginal donors are now used to expand pool of organs. As a consequence, the development of better organ preservation methods remains a major target and deserves scientific consideration.     

Organ preservation: experience with University of Wisconsin solution and plans for the future

Transplantation of organs continues to be a primary therapeutic modality for treatment of end-stage organ disease, and 1-year graft survival rates show increasing improvements for most organs. A number of transplant centers show 1-yr graft survival rates approaching 90% or more for the kidney, liver and pancreas. Rejection continues to be the major cause for loss of organs and there is still a major shortage of organs for transplantation. Additionally, many organs showed delayed graft function (or primary nonfunction) which may be related to either donor factors or preservation factors. The University of Wisconsin solution for organ preservation has increased the safe time of preservation for the liver, kidney, and pancreas and helped to increase the quality and number of organs available for transplantation. However, the long-range goal of organ preservation (unlimited preservation) is still far from being reached. In the past, preservation could accurately be categorized as an art and preservation solutions were developed based upon theoretical rationales about the mechanisms of organ injury at hypothermia and what agents would suppress injury. The utility and success of this approach is exemplified by the developments of Collins solution and the UW solution. However, further developments in methods to increase the quality and duration of preservation of all transplantable organs would appear to be dependent upon defining, systematically, how organs are injured and what can be done to suppress the injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Organ preservation

Organ preservation is currently performed by simple cold storage or continuous hypothermic perfusion. Cold storage using University of Wisconsin (UW) solution greatly prolongs the successful preservation period for abdominal organs such as the kidney, liver, and pancreas. Thoracic organs (heart, lung), however, can be preserved for only several hours even with UW solution. As a result of improvements in organ transplantation, the number of patients on waiting lists has grown rapidly. Unfortunately, many patients die while waiting for donor organs, and expansion of the donor pool is mandatory. Possible solutions to the shortage of donor organs include the use of marginal donors and non-heart-beating donors. For this purpose, more sophisticated methods of organ preservation are needed, and therefore extensive investigations using current technologies including gene transfer should be performed. Every effort should be made to accommodate the preferences of donors.     

不同器官保存液对成人胰岛分离、纯化及功能的影响

目的探讨不同器官保存液保存胰腺对胰岛分离、纯化及功能的影响。方法以成人胰腺为研究对象,分别以高渗枸橼酸钾溶液(HCA液)与威斯康新大学器官保存液(UW液)灌洗、保存胰腺,进行胰岛分离及纯化,比较两组分离、纯化后收获的胰岛数及胰岛当量数(IEQ),并在体外评价其功能。结果两组在胰腺重量、热缺血时间、冷缺血时间没有明显差异的情况下,胰腺分离、纯化后所获得的胰岛数及胰岛当量数的差异无显著性(P>0.05),纯化后的胰岛细胞在体外低糖与高糖刺激下,其胰岛素的分泌量及C肽的释放量的差异也无显著性(P>0.05);两个组胰岛细胞的活率均在85%以上。结论在胰岛移植中,可以使用HCA液作为胰腺保存液。     

An automated and portable low-flow pulsatile perfusion system for organ preservation

While machine preservation reduces the incidence of delayed graft function in renal transplant recipients, it is only used in 10% of kidney transplantations. The performance of our portable, lowflow-pulsatile organ perfusion system was examined in a canine kidney autotransplantation model. Grafts were stored for 72 h by simple cold preservation in University of Wisconsin (UW) solution, or by high or low-flow machine preservation. After preservation, the grafts were autotransplanted and the animals were followed for 15 days. Graft function was better in machine-preserved kidneys. Tissue biochemistry indicated that machine preservation resulted in higher levels of adenine nucleotides and better histological integrity than the cold storage. While histology and biochemistry of machine-preserved groups were similar, electromicroscopy of high-flow grafts showed mild accumulation of intravenous debris and endothelial swelling. This study shows that a simplified machine perfusion technique is effective for organ preservation.     

Multi-organ procurement utilizing cardiopulmonary bypass and profound hypothermic circulatory arrest

Despite advances in preservation solutions, hypothermia remains a critical component of organ preservation for transplantation. Many surgeons involved in multi-organ procurement procedures have expressed concern about the possible detrimental effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on non-thoracic transplant organ function. In order to assess the validity of these concerns, a review of 20 multi-organ harvest procedures performed utilizing cardiopulmonary bypass and profound hypothermic circulatory arrest was undertaken. In all instances this technique was combined with organ flushing utilizing cold preservation solution. Adequate data was available to assess post-transplant organ function of all organs recovered in 16 procedures. Indication for the use of this technique was procurement of a heart-lung bloc in 16 instances and donor instability (hypotension) refractory to volume loading and inotropic agents in 4 instances. Organs obtained, including all organs from unstable donors which would otherwise have been lost, functioned, acceptably. Additionally, blood drained into the pump was used for recipient transfusion in 8 instances. This report documents that cardiopulmonary bypass and profound hypothermic circulatory arrest may be easily combined with traditional procurement flushing techniques and it provides excellent organ preservation for subsequent transplantation. This approach can optimize organ recovery from hemodynamically unstable donors, increasing the number available for transplantation.     

An In Vivo Autotransplant Model of Renal Preservation: Cold Storage Versus Machine Perfusion in the Prevention of Ischemia/Reperfusion Injury

There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation.
Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion ( n  = 6) or cold storage ( n  = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5'-triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation.
The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys.
The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage.