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First transplantation of a pig heart from a multiple gene-modified donor, porcine cytomegalovirus/roseolovirus, and antiviral drugs. 首次移植来自多基因修饰供体的猪心脏,猪巨细胞病毒/玫瑰病毒,以及抗病毒药物。
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-05-01 DOI: 10.1111/xen.12800
Joachim Denner
The porcine cytomegalovirus (PCMV) is actually a porcine roseolovirus (PRV).1 As the official International Committee on Taxonomy of Viruses (ITCV) name, suid betaherpesvirus 2 (SuBHV2),2 is not widely used, the abbreviation (PCMV/PRV) will be used to make clear that it is a herpesvirus not closely related to the human cytomegalovirus (HCMV), but to the human herpesviruses 6 and 7 (HHV-6, HHV7), which are also roseoloviruses.3 PCMV/PRV was shown to reduce significantly the survival time of pig xenotransplants in non-human primates. Yamada et al.4 and Sekijima et al.5 reported a reduction of the survival time of pig kidneys from PCMV/PRV-positive donor pigs when transplanted in cynomolgus monkeys and baboons, respectively, in 2014. Already in 2002 Mueller et al.6 reported an activation PCMV in a pig-to-primate model of xenotransplantation in animals with short survival times. In 2016 for the first time an active replication of PCMV following transplantation of a pig heart into a baboon despite undetected virus in the donor pig was reported.7 Denner et al.8 reported a reduction of the survival time of genetically modified pig hearts in baboons. For detailed reviews of these and other studies see Denner.9,10 PCMV/PRVwas also transmitted to the human recipient who received a pig heart in January 2022 in Baltimore, Maryland, USA.11 The clinical features and the steadily increasing virus load observed in the patient in Baltimore are very similar to the features and high virus load observed in baboons, which received a PCMV/PRV-positive heart in Munich.8 Therefore, it is likely that the virus contributed together with other factors to the death of the
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引用次数: 2
Patients' opinions 10 years after receiving encapsulated porcine islet xenotransplantation without immunosuppression. 无免疫抑制的猪胰岛包膜异种移植术后10年患者意见
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-05-01 DOI: 10.1111/xen.12798
Shinichi Matsumoto, Adrian Abalovich, Shaun Wynyard, Mariana E Carulla, David Abalovich

Background: Previously we performed clinical encapsulated neonatal porcine islet transplantation under comprehensive regulation, and demonstrated the efficacy and safety. To analyze the patients' quality of life (QOL), we assessed patients' opinions 10 years after islet xenotransplantation.

Methods: Twenty-one type 1 diabetic patients received microencapsulated neonatal porcine islet transplants in Argentina were enrolled. Seven patients were enrolled in efficacy and safety study and 14 patients were enrolled in safety studies. Patients' opinions related to the current and pre-transplant status of diabetes control, blood glucose levels, severe hypoglycemia, and hyperglycemia required hospitalization were analyzed. In addition, opinions related to islet xenotransplantation were assessed.

Results: At the time of this survey, average HbA1c was still significantly lower compared to pre-transplantation (8.5 ± 0.9 (%) at pre-transplant and 7.4 ± 0.5(%) at the survey, p < .05) and average insulin dose were also lower (0.95 ± 0.32 (IU/kg) at pre-transplant and 0.73 ± 0.27 (IU) at the survey). The majority of patients improved diabetes control (71%), blood glucose levels (76%), severe hypoglycemia (86%) and hyperglycemia required hospitalization (76%), and no patients deteriorated in all of the categories when compared with pre-transplantation. No patients had cancer, or psychological problem, and one patient had a serious adverse event. The majority of patients wanted to recommend this treatment to other patients (76%) and receive booster transplantation (85.7%).

Conclusions: The majority of patients had positive opinions related to the encapsulated porcine islet xenotransplantation 10 years after transplantation.

背景:我们在综合调控下进行了新生儿猪胰岛包膜移植,并证实了其有效性和安全性。为了分析患者的生活质量(QOL),我们评估了患者对异种胰岛移植后10年的看法。方法:选取21例阿根廷1型糖尿病患者接受新生儿猪胰岛微囊化移植。7例患者入组了疗效和安全性研究,14例患者入组了安全性研究。分析患者对目前及移植前糖尿病控制状况、血糖水平、严重低血糖及高血糖需要住院治疗的意见。此外,还评估了与胰岛异种移植有关的意见。结果:调查时,平均HbA1c仍明显低于移植前(移植前8.5±0.9(%),调查时7.4±0.5(%))。结论:大多数患者在移植后10年对包膜猪岛异种移植持积极态度。
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引用次数: 2
Xenotransplantation literature update March 2021-March 2023. 异种移植文献更新2021年3月- 2023年3月。
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-05-01 DOI: 10.1111/xen.12805
Shani Kamberi, Raphael P H Meier

After a significant hiatus imposed by the COVID-19 pandemic, we hereby restart Xenotransplantation literature updates. With the recently performed clinical xenotransplantation cases and the much-heightened interest in the field, we have determined that this is an optimal time to reinstate this section. There has been an invigorated focus on unique challenges posed by pig-to-human xenotransplantation, and specific attention will be given to this aspect. In this issue, we aimed to cover the gap and compiled the most relevant publications from March 2021 to March 2023.

在COVID-19大流行造成的重大中断之后,我们在此重新启动异种移植文献更新。随着最近进行的临床异种移植病例和对该领域的高度兴趣,我们决定现在是恢复该部分的最佳时机。猪到人异种移植带来的独特挑战已经得到了极大的关注,并将特别关注这方面。在本期中,我们旨在弥补这一空白,并汇编了2021年3月至2023年3月期间最相关的出版物。
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引用次数: 1
Issue Information 问题信息
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-05-01 DOI: 10.1111/xen.12755
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引用次数: 0
Xenotransplantation: A historical-ethical account of viewpoints. 异种移植:观点的历史伦理叙述。
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-03-01 Epub Date: 2023-03-21 DOI: 10.1111/xen.12797
Daniel Rodger, Daniel J Hurst, David Kc Cooper

Formal clinical trials of pig-to-human organ transplant-known asxenotransplantation-may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical-ethical account of xenotransplantation and details if or how viewpoints have shifted over time.

被称为异种器官移植的猪对人器官移植的正式临床试验可能在本十年开始,首批试验可能由成人肾移植或儿童心脏移植患者组成。异种移植作为一项系统的科学研究只能追溯到20世纪后半叶,在此之前发生了偶发性的异种移植事件。随着异种移植科学在20世纪和21世纪的发展,公众对潜在疗法的了解也在增加。随着这一点,在关键领域,对异种移植的伦理立场发生了变化,例如宗教和公众对异种移植、动物权利和公共卫生问题的看法。这篇综述提供了异种移植的历史伦理描述,并详细说明了观点是否或如何随着时间的推移而发生变化。
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引用次数: 0
Attitudes of patients with renal disease on xenotransplantation: A systematic review. 肾病患者对异种移植的态度:系统综述。
IF 3.3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-03-01 Epub Date: 2023-03-07 DOI: 10.1111/xen.12794
Isabel DeLaura, Imran J Anwar, Joseph Ladowski, Alejandra Patino, Sarah Cantrell, Scott Sanoff

Background: Recent years have seen major advancements in xenotransplantation: the first pig-to-human heart transplant, the development of a brain-dead recipient model for kidney xenotransplantation, and the registration of the first xenokidney clinical trial. The attitudes of patients with kidney disease or transplants on xenotransplantation and an assessment of their reservations and considerations regarding the technology are crucial to successful clinical translation and eventual widespread implementation.

Methods: This systematic review was registered through PROSPERO (CRD42022344581) prior to initiation of the study and reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. We included studies that evaluated attitudes towards and willingness to undergo xenotransplantation in patients with end-stage renal disease (ESRD), including those who had already undergone transplantation. MEDLINE (via Ovid), Embase (via Elsevier), and Web of Science (via Clarivate) were searched from database inception to July 15, 2022 by an experienced medical librarian for studies on xenotransplantation and attitudes. Abstracts and full text were screened using Covidence software and data items regarding study methodology, patient demographics, and attitudes regarding xenotransplantation were extracted using Microsoft Excel. Risk of bias assessments were performed using the Critical Appraisal Skills Programmed and National Institute of Health study quality assessment tools.

Results: Of 1992 studies identified, 14 studies met the inclusion criteria. These studies were conducted across eight countries, four in the United States, for a total of 3114 patients on the kidney waitlist or with a kidney transplant. All patients were over 17 years old and 58% were male. Acceptance of a xenotransplant was assessed using surveys in 12 studies. Sixty-three percent (n = 1354) of kidney patients reported that they would accept a xenotransplant with function comparable to that of an allotransplant. Acceptance of xenografts with inferior function to allografts (15%) or as bridge organs (35%) to allotransplantation was lower. Specific concerns expressed by patients included graft function, infection, social stigma, and animal rights. Subgroup analyses showed higher acceptance in already transplanted compared to waitlist patients and white compared to Black Americans.

Conclusion: An understanding of patient attitudes and reservations is key to the successful execution of the first xenotransplantation clinical trials. This study compiles important factors to consider, such as patient concerns, attitudes regarding practical clinical scenarios for the use of xenotransplantation, and the impact of demographic factors on acceptance of this emerging technology.

背景:近年来,异种移植取得了重大进展:首次猪对人心脏移植、开发出用于肾脏异种移植的脑死亡受体模型,以及登记了首个异种肾脏临床试验。肾脏疾病或移植患者对异种移植的态度,以及他们对该技术的保留意见和考虑因素的评估,对于成功的临床转化和最终的广泛实施至关重要:本系统综述在研究开始前通过 PROSPERO(CRD42022344581)进行了注册,并采用系统综述和荟萃分析首选报告项目(PRISMA)指南进行报告。我们纳入了评估终末期肾病 (ESRD) 患者(包括已接受移植手术的患者)对异种移植的态度和意愿的研究。由一位经验丰富的医学图书管理员对MEDLINE(通过Ovid)、Embase(通过Elsevier)和Web of Science(通过Clarivate)进行了检索,检索时间为数据库建立至2022年7月15日,检索内容包括异种移植和态度方面的研究。使用Covidence软件筛选摘要和全文,并使用Microsoft Excel提取有关研究方法、患者人口统计学和异种器官移植态度的数据项。使用 "批判性评估技能计划 "和美国国立卫生研究院研究质量评估工具对偏倚风险进行评估:在确定的 1992 项研究中,有 14 项研究符合纳入标准。这些研究在 8 个国家进行,其中 4 个国家在美国,共有 3114 名肾脏候选者或肾移植患者。所有患者的年龄都在 17 岁以上,58% 为男性。12项研究通过调查评估了患者对异种移植的接受程度。63%的肾脏病人(n = 1354)表示,他们愿意接受功能与异体移植相当的异体移植。接受功能不如同种异体移植(15%)或作为同种异体移植的桥梁器官(35%)的患者比例较低。患者表达的具体担忧包括移植物功能、感染、社会耻辱感和动物权利。亚组分析显示,已经接受移植的患者比等待移植的患者接受度高,美国白人比美国黑人接受度高:结论:了解患者的态度和保留意见是成功实施首例异种移植临床试验的关键。本研究汇集了需要考虑的重要因素,如患者的顾虑、对使用异种器官移植的实际临床方案的态度,以及人口统计因素对接受这项新兴技术的影响。
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引用次数: 0
Large-gap peripheral nerve repair using xenogeneic transplants in rhesus macaques. 异种移植修复恒河猴大间隙周围神经。
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-03-01 DOI: 10.1111/xen.12792
Paul Holzer, Elizabeth J Chang, Kaitlyn Rogers, Jamie Tarlton, Diana Lu, Natasha Gillespie, Jon Adkins, Monica Metea, Alan LaRochelle, Joan Wicks, Buket Onel, Steve Gullans, Joshua C Doloff, Linda Scobie, Curtis L Cetrulo, Rod Monroy

Surgical intervention is required to successfully treat severe, large-gap (≥4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human and porcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT-KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, and importantly, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials similar to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our preliminary findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross-species cells, and highlight the broader clinical potential of xenotransplantation.

成功治疗严重的大间隙(≥4cm)周围神经损伤需要手术干预。然而,所有现有的治疗方法都有缺点,需要一种替代自体神经的方法。人和猪的神经在生理上相似,具有相似的尺寸和结构,雪旺细胞的存在和分布,以及细胞外基质(ECM)的保守特征。我们报道了10只恒河猴的桡骨神经全断的修复,使用的是来自基因工程(GalT-KO)、指定无病原体(DPF)猪供体的完整坐骨神经。这导致了截断神经的再生,更重要的是,腕关节伸展功能的恢复,远端肌肉神经再生,神经传导速度和复合肌肉动作电位的恢复与自体对照相似。我们还证明了免疫排斥,系统性猪细胞迁移和可检测的残留猪物质的缺失。我们的初步研究结果支持活的猪神经移植的安全性和有效性,提示跨物种细胞的可互换治疗用途,并强调异种移植的更广泛的临床潜力。
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引用次数: 1
Issue Information 问题信息
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-03-01 DOI: 10.1111/xen.12752
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引用次数: 0
Systemic inflammation in the xenotransplant recipient (SIXR) can occur in the absence of pCMV infection. 在没有 pCMV 感染的情况下,异种移植受体也会出现全身炎症(SIXR)。
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-03-01 Epub Date: 2023-02-28 DOI: 10.1111/xen.12796
Mohamed B Ezzelarab, Hidetaka Hara, David Ayares, David K C Cooper
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引用次数: 0
Xenotransplantation of pig islet cells: Potential adverse impact of virus infections on their functionality and insulin production. 猪胰岛细胞异种移植:病毒感染对其功能和胰岛素产生的潜在不利影响
IF 3.9 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-03-01 DOI: 10.1111/xen.12789
Joachim Denner
alle-viate
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引用次数: 1
期刊
Xenotransplantation
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