Pig-to-human heart xenotransplantation in two recently deceased human recipients

Moazami, Nader; Stern, Janet; Khalil, Karen; Kim, Jacqueline I.; Narula, Navneet; Mangiola, Massimo; Weldon, Elaina; Kagermazova, Larisa; James, Louis; Lawson, Nikki; Piper, Greta L.; Sommer, Philip; Reyentovich, Alex; Bamira, Daniel; Saraon, Tajinderpal; Kadosh, Bernard; DiVita, Michael; Goldberg, Randal I.; Hussain, Syed T.; Chan, Justin; Ngai, Jennie; Jan, Thomas; Ali, Nicole; Tatapudi, Vasishta; Segev, Dorry L.; Bisen, Shivani; Jaffe, Ian; Piegari, Benjamin; Kowalski, H.; Kokkinaki, Maria; J, Monahan; Sorrells, Lori; Burdorf, Lars; Boeke, Jef D.; Pass, Harvey I.; Goparaju, Chandra; Keating, Brendan J.; Ayares, David; Lorber, Marc I.; Griesemer, Adam; Mehta, Sapna A.; Smith, Deane E.; Montgomery, Robert A.

doi:10.1038/s41591-023-02471-9

Cited by 46 publications

(19 citation statements)

References 40 publications

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“…77 After the first xenotransplantation with genetically modified pig hearts 78 in 2022, the results of two transplantations using gene-edited pig hearts transplanted into brain-dead human recipients were published in 2023. 79 Both xenografts demonstrated excellent cardiac function after early after transplantation and continued to function for the duration of the observation. Cardiac function in one of the hearts declined postoperatively, attributed to a size mismatch.…”

Section: Surgery For Terminal Heart Failurementioning

confidence: 89%

Cardiac Surgery 2023 Reviewed

Kirov,

Caldonazo,

Mukharyamov

et al. 2024

Thorac Cardiovasc Surg

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We reviewed the cardiac surgical literature for 2023. PubMed displayed almost 34,000 hits for the search term “cardiac surgery AND 2023.” We used a PRISMA approach for a results-oriented summary. Key manuscripts addressed the mid- and long-term effects of invasive treatment options in patient populations with coronary artery disease (CAD), comparing interventional therapy (percutaneous coronary intervention [PCI]) with surgery (coronary artery bypass graft [CABG]). The literature in 2023 again confirmed the excellent long-term outcomes of CABG compared with PCI in patients with left main stenosis, specifically in anatomically complex chronic CAD, but even in elderly patients, generating further support for an infarct-preventative effect as a prognostic mechanism of CABG. For aortic stenosis, a previous trend of an early advantage for transcatheter (transcatheter aortic valve implantation [TAVI]) and a later advantage for surgical (surgical aortic valve replacement) treatment was also re-confirmed by many studies. Only the Evolut Low Risk trial maintained an early advantage of TAVI over 4 years. In the mitral and tricuspid field, the number of interventional publications increased tremendously. A pattern emerges that clinical benefits are associated with repair quality, making residual regurgitation not irrelevant. While surgery is more invasive, it currently generates the highest repair rates and longest durability. For terminal heart failure treatment, donor pool expansion for transplantation and reducing adverse events in assist device therapy were issues in 2023. Finally, the aortic diameter related to adverse events and technical aspects of surgery dominated in aortic surgery. This article summarizes publications perceived as important by us. It cannot be complete nor free of individual interpretation, but provides up-to-date information for patient-specific decision-making.

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Section: Surgery For Terminal Heart Failurementioning

confidence: 89%

Cardiac Surgery 2023 Reviewed

Kirov,

Caldonazo,

Mukharyamov

et al. 2024

Thorac Cardiovasc Surg

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“…In both cases, there was an excellent cardiac function immediately after transplantation, although cardiac function declined postoperatively in one case, possibly due to size mismatch between donor and recipient. In any case, the explanted hearts did not evidence cellular or antibody-mediated rejection [ 58 ].…”

Section: Recent Clinical Studiesmentioning

confidence: 99%

Current challenges in xenotransplantation

Vadori,

Cozzi

2024

Current Opinion in Organ Transplantation

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Purpose of review In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and methodologies developed to overcome potential obstacles that may preclude the translation and successful application of clinical xenotransplantation. Recent findings Preclinical studies have demonstrated that it is now possible to extend beyond two years survival of primate recipients of life saving xenografts. This has been accomplished thanks to the utilization of genetic engineering methodologies that have allowed the generation of specifically designed gene-edited pigs, a careful donor and recipient selection, and appropriate immunosuppressive strategies. In this light, the compassionate use of genetically modified pig hearts has been authorized in two human recipients and xenotransplants have also been achieved in human decedents. Although encouraging the preliminary results suggest that several challenges have yet to be fully addressed for a successful clinical translation of xenotransplantation. These challenges include immunologic, physiologic and biosafety aspects. Summary Recent progress has paved the way for the initial compassionate use of pig organs in humans and sets the scene for a wider application of clinical xenotransplantation.

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“…However, viral safety was overlooked during this xenotransplantation process, leading to the transmission of pig viruses (PCMV/PRV) to human recipients, resulting in patient fatalities [ 73 ]. In July 2023, Nader Moazami et al transplanted hearts from 10 gene-edited pigs into two brain-dead human recipients and meticulously monitored transplant function, pre-existing xenoreactivity antibody injury, hemodynamics, and systemic reactions within 66 h. They found no safety risks in the deceased recipients [ 74 ]. While progress has been made, it’s clear we're not fully prepared for human xenotransplantation.…”

Section: Gene-edited Pig Organ Transplantation Modelmentioning

confidence: 99%

Complement networks in gene-edited pig xenotransplantation: enhancing transplant success and addressing organ shortage

Yuan,

Cui,

Zhao

et al. 2024

J Transl Med

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The shortage of organs for transplantation emphasizes the urgent need for alternative solutions. Xenotransplantation has emerged as a promising option due to the greater availability of donor organs. However, significant hurdles such as hyperacute rejection and organ ischemia–reperfusion injury pose major challenges, largely orchestrated by the complement system, and activated immune responses. The complement system, a pivotal component of innate immunity, acts as a natural barrier for xenotransplantation. To address the challenges of immune rejection, gene-edited pigs have become a focal point, aiming to shield donor organs from human immune responses and enhance the overall success of xenotransplantation. This comprehensive review aims to illuminate strategies for regulating complement networks to optimize the efficacy of gene-edited pig xenotransplantation. We begin by exploring the impact of the complement system on the effectiveness of xenotransplantation. Subsequently, we delve into the evaluation of key complement regulators specific to gene-edited pigs. To further understand the status of xenotransplantation, we discuss preclinical studies that utilize gene-edited pigs as a viable source of organs. These investigations provide valuable insights into the feasibility and potential success of xenotransplantation, offering a bridge between scientific advancements and clinical application.

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Pig-to-human heart xenotransplantation in two recently deceased human recipients

Cited by 46 publications

References 40 publications

Cardiac Surgery 2023 Reviewed

Cardiac Surgery 2023 Reviewed

Current challenges in xenotransplantation

Complement networks in gene-edited pig xenotransplantation: enhancing transplant success and addressing organ shortage

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