Kidney xenotransplantation: Recent progress in preclinical research

Deng, Wenyi; Jiang, Hai; Li, Tao; Wang, Yi

doi:10.1016/j.cca.2020.11.028

Cited by 9 publications

(7 citation statements)

References 115 publications

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“…When comparing both, it is difficult to defend the latter without reservations. Other authors agree with this assessment [ 85 , 86 ].…”

Section: Discussionsupporting

confidence: 74%

Kidney Xenotransplantation: Are We Ready for Prime Time?

Santos

2023

Curr Urol Rep

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Purpose of Review With the exponential increase in interest and great strides toward clinical application, many experts believe we are ready for kidney xenotransplant human trials. In this review, we will examine the obstacles overcome and those yet to be conquered, discussing the human trials performed and the questions they raised. Additionally, we will revisit overlooked aspects that may be crucial for improvements and suggest future approaches for xenotransplant research. Recent Findings Improving survival in pig-to-non-human-primate models with the identification of an ideal immunosuppression regimen led to 3 cases of kidney xenotransplant in brain-dead humans with limited follow-up and a single clinical case of pig-to-human heart xenotransplant with 2-month survival. Summary With limited human results and unlimited potential, xenotransplantation shines a beacon of hope for a brighter future. However, we must navigate through the complexities of balancing scientific progress and patient welfare, avoiding being blinded by xenotransplantation’s unquestionable potential.

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“…When comparing both, it is difficult to defend the latter without reservations. Other authors agree with this assessment [ 85 , 86 ].…”

Section: Discussionsupporting

confidence: 74%

Kidney Xenotransplantation: Are We Ready for Prime Time?

Santos

2023

Curr Urol Rep

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“…Xenotransplantation using pig cells, tissues, or organs is regarded as the next great medical revolution [157]. PERVs are integrated in the genome of all pigs; they can be released as infectious particles, and some of them can infect human cells, therefore posing a risk for xenotransplantation.…”

Section: Discussionmentioning

confidence: 99%

Porcine Endogenous Retroviruses and Xenotransplantation, 2021

Denner

2021

Viruses

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Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and some of them are able to infect human cells. Therefore, PERVs pose a risk for xenotransplantation, the transplantation of pig cells, tissues, or organ to humans in order to alleviate the shortage of human donor organs. Up to 2021, a huge body of knowledge about PERVs has been accumulated regarding their biology, including replication, recombination, origin, host range, and immunosuppressive properties. Until now, no PERV transmission has been observed in clinical trials transplanting pig islet cells into diabetic humans, in preclinical trials transplanting pig cells and organs into nonhuman primates with remarkable long survival times of the transplant, and in infection experiments with several animal species. Nevertheless, in order to prevent virus transmission to the recipient, numerous strategies have been developed, including selection of PERV-C-free animals, RNA interference, antiviral drugs, vaccination, and genome editing. Furthermore, at present there are no more experimental approaches to evaluate the full risk until we move to the clinic.

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“…In summary, the added expression of several hCRPs in GTKO transgenic pigs can further prevent rejection development [ 82 ]. With continuous scientific efforts, life-sustaining kidney xenotransplantation is much closer to clinical reality than previously thought.…”

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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Kidney xenotransplantation: Recent progress in preclinical research

Cited by 9 publications

References 115 publications

Kidney Xenotransplantation: Are We Ready for Prime Time?

Kidney Xenotransplantation: Are We Ready for Prime Time?

Porcine Endogenous Retroviruses and Xenotransplantation, 2021

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

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