Scientific and psychosocial ethical considerations for initial clinical trials of kidney xenotransplantation

Hurst, Daniel J.; Padilla, Luz A.; Cooper, D. K. C.; Paris, Wayne

doi:10.1111/xen.12722

Cited by 13 publications

(7 citation statements)

References 23 publications

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“…In addition, informing bystanders would respect their autonomy as free agents to choose whether to accept this risk for themselves. We have recently argued that a fundamental component of xenotransplantation research design is for certain bystanders to assent to the risks 28 . This may be impractical, but at least all of those who it is anticipated will be in close or frequent contact with the patient should be educated on the potential risks.…”

Section: Minimization Of the Risk Of A Xenozoonosis To Bystandersmentioning

confidence: 99%

“…Over many years, much has been written on the ethical issues attendant with xenotransplantation 4–10 . However, not every ethical issue associated with xenotransplantation, for example, permissibility of using animals to meet human needs, or how xenografts and allografts will be allocated to patients, will be resolved in the near‐term.…”

Section: Introductionmentioning

confidence: 99%

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Pressing ethical issues relating to clinical pig organ transplantation studies

Hurst,

Cooper

2024

Xenotransplantation

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Clinical pig heart transplant experiments have been undertaken, and further clinical experiments and/or clinical trials of gene‐edited pig organ xenotransplantation are anticipated. The ethical issues relating to xenotransplantation have been discussed for decades but with little resolution. Consideration of certain ethical issues is more urgent than others, and the need to attain consensus is important. These issues include: (i) patient selection criteria for expanded access and/or clinical trials; (ii) appropriate protection of the patient from xenozoonoses, that is, infections caused by pig microorganisms transferred with the organ graft, (iii) minimization of the risk of a xenozoonosis to bystanders, and (iv) the need for additional public perception studies. We discuss why it is important and urgent to achieve consensus on these ethical issues prior to carrying out further expanded access experiments or initiating formal clinical trials. The ways forward on each issue are proposed.

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Section: Minimization Of the Risk Of A Xenozoonosis To Bystandersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pressing ethical issues relating to clinical pig organ transplantation studies

Hurst,

Cooper

2024

Xenotransplantation

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“…Unlike many novel therapies, xenotransplantation presents the small but potentially consequential risk of xenozoonosis—the transmission of a pathogenic microorganism from the porcine graft to the xenograft recipient and possibly from the recipient to the public. This could potentially put at risk those who have no special or close relationship with the patient, a group termed “bystanders” [5]. These potential risks must therefore be made known during the informed consent process to individuals who potentially may participate in xenotransplantation clinical trials and also to the communities in which clinical trials are being planned so that dialogue can take place.…”

Section: The Importance Of Public Engagementmentioning

confidence: 99%

The importance of public engagement in clinical xenotransplantation

Hurst,

Cooper

2024

Health Care Science

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Over the past several decades, significant scientific progress in xenotransplantation has brought the field to the threshold of clinical trials. In the past 3 years in the United States, experimental pig kidney and heart xenotransplantation have been performed on human subjects recently declared dead by neurological criteria (decedents). In addition, two pig heart transplants have been carried out in living patients under the United States Food and Drug Administration's expanded access guidelines. However, though there has been a flurry of activity there remain unanswered questions regarding how the public views xenotransplantation, what concerns may exist, and how to address these concerns in a meaningful way. This paper aims to underscore the importance of public engagement in xenotransplantation, emphasizing the ongoing need for studies to assess public opinions. The current evidence on public engagement studies is reviewed and gaps in our understanding are identified. We propose practical steps to advance this field. Additional studies to determine the extent of racial/ethnic differences in attitudes to xenotransplantation should be conducted. Empirical and descriptive analysis of certain religious viewpoints—especially minority faiths—would be valuable. As public engagement is an important aspect of public acceptance of novel research that is accompanied by risk, we suggest that xenotransplantation biotechnology companies might consider leading the way in funding this research.

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“…There are many ethical considerations and regulatory aspects in xenotransplantation, particularly with respect to patient consent and autonomy. These issues were previously discussed in detail (54,55). Briefly, in patients with chronic liver failure who retain capacity to make their own medical decisions the issue of patient consent is straightforward.…”

Section: Patient Consentmentioning

confidence: 99%

Current Barriers to Clinical Liver Xenotransplantation

et al. 2022

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Preclinical trials of pig-to-nonhuman primate liver xenotransplantation have recently achieved longer survival times. However, life-threatening thrombocytopenia and coagulation dysregulation continue to limit preclinical liver xenograft survival times to less than one month despite various genetic modifications in pigs and intensive pharmacological support. Transfusion of human coagulation factors and complex immunosuppressive regimens have resulted in substantial improvements in recipient survival. The fundamental biological mechanisms of thrombocytopenia and coagulation dysregulation remain incompletely understood. Current studies demonstrate that porcine von Willebrand Factor binds more tightly to human platelet GPIb receptors due to increased O-linked glycosylation, resulting in increased human platelet activation. Porcine liver sinusoidal endothelial cells and Kupffer cells phagocytose human platelets in an asialoglycoprotein receptor 1-dependent and CD40/CD154-dependent manner, respectively. Porcine Kupffer cells phagocytose human platelets via a species-incompatible SIRPα/CD47 axis. Key drivers of coagulation dysregulation include constitutive activation of the extrinsic clotting cascade due to failure of porcine tissue factor pathway inhibitor to repress recipient tissue factor. Additionally, porcine thrombomodulin fails to activate human protein C when bound by human thrombin, leading to a hypercoagulable state. Combined genetic modification of these key genes may mitigate liver xenotransplantation-induced thrombocytopenia and coagulation dysregulation, leading to greater recipient survival in pig-to-nonhuman primate liver xenotransplantation and, potentially, the first pig-to-human clinical trial.

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Scientific and psychosocial ethical considerations for initial clinical trials of kidney xenotransplantation

Cited by 13 publications

References 23 publications

Pressing ethical issues relating to clinical pig organ transplantation studies

Pressing ethical issues relating to clinical pig organ transplantation studies

The importance of public engagement in clinical xenotransplantation

Current Barriers to Clinical Liver Xenotransplantation

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