ABSTRACT
Purpose
The objective of this review is to map and synthesize the existing literature regarding informed consent for porcine islet xenotransplantation for the treatment of Type 1 Diabetes.
Methods
The search was conducted in May 2025 through the following databases: PubMed, SCOPUS, EMBASE, and CINAHL. Broad search strings were used to combine the text words “islet” AND “xenotransplantation” AND “consent” or similar permutations and combinations. Peer‐reviewed articles were included if they were published between January 1990 and May 2025 and written in English. The final search results were manually exported to a reference manager system (Zotero), and the PRISMA‐ScR flow diagram was created to depict the data extraction process.
Results
From 134 sources, 7 articles met eligibility for this scoping review. Although clinical studies have been sporadically conducted, there is a lack of literature describing informed consent for islet xenotransplantation.
Conclusion
This review highlighted a scarcity of scholarly discourse and published guidance on informed consent specifically in the context of islet xenotransplantation.
Keywords: ethics, informed consent, islets, type 1 diabetes, xenotransplantation
1. Introduction
Type 1 diabetes (T1D) is a chronic autoimmune condition affecting over 8 million people globally. Pancreatic beta cell islet xenotransplantation is a potential alternative to lifelong insulin therapy and islet allotransplantation. While informed consent for solid organ xenotransplantation is well‐addressed [1, 2, 3, 4], it is unclear that a similar breadth and depth of work has been conducted for islet xenotransplantation. We conducted a review to (i) understand the state of informed consent for islet xenotransplantation, and (ii) identify key ethical considerations and gaps.
2. Methods
This review followed the PRISMA‐ScR checklist and the protocol was registered in OSF: https://osf.io/68vpc/.
2.1. Search Strategy
Investigators searched PubMed, SCOPUS, EMBASE, and CINAHL in May 2025 using broad search strings for “islet,” “xenotransplantation,” and “consent.”
2.2. Inclusion and Exclusion Criteria
To be eligible for inclusion in this review, articles must discuss the topic of informed consent specifically as it relates to islet cell xenotransplantation. Sources may be included if they are normative, descriptive, or empirical, and journal articles, chapters in edited volumes, as well as abstracts presented at conferences. Sources were included if they were published between January 1990‐May 2025, written in English, and specifically discussed informed consent for islet xenotransplantation. Pre‐clinical studies were excluded.
3. Results
The final search results were exported to a reference manager system (Zotero). After removing duplicates, 134 sources remained for initial screening of titles and abstracts (Figure 1). Following this, the full text of 20 articles were screened for eligibility and 7 were retained for inclusion in this review. The search and screening process is described in Figure 1. The articles included for review are summarized in Table 1. Key findings were synthesized into four themes, described below.
FIGURE 1.
PRISMA‐ScR flow diagram.
TABLE 1.
Included articles.
| Author(s) | Year | Journal | Article type | Main findings |
|---|---|---|---|---|
| Rood and Cooper | 2006 | American Journal of Transplantation | Viewpoint | There is insufficient convincing experimental data from non‐human primate models to warrant further clinical trials of islet xenotransplantation. To justify future trials, more experimental data documenting efficacy and safety of the procedure, particularly regarding porcine viruses, are needed from non‐human primate studies. Even then, a carefully monitored clinical trial would carry potential risk to patients and society. |
| Ellis and Korbutt | 2015 | Xenotransplantation | Review | There is a duality to informed consent that should involve both the recipient and the public that also carries the burden of risk. With the expected unlimited supply of islet cells, clinical trials are justified to continue after obtaining the proper informed consent. |
| Marckmann and Thiersch | 2017 | Xenotransplantation | Qualitative interview study; conference abstract | There was strong acceptance toward xenotransplantation by participants. Participants raised concerns about infectious disease risks, slaughtering of animals, and perceived social stigma, all of which the authors recommend should be taken into account during the informed consent process. |
| Goerlich et al. | 2019 | Current Opinion in Organ Transplantation | Review | An ethically sound informed consent process for xenotransplantation must include transparent, lifelong obligations for participants. |
| Kogel et al. | 2021 | BMC Medical Ethics | Qualitative interview study | The interviews of seven patients with T1D concluded that the informed consent process must include trust and transparency for the patients to make an educated medical decision. Islet xenotransplantation is sustainable if it does not excessively restrict the patient's life. Even with the proper informed consent, patients view xenotransplantation as a last resort to manage their diabetes. |
| De Jongh et al. | 2023 | Transplant International | Review | Patient desperation poses a challenge to genuine informed consent. A comprehensive and interdisciplinary approach is needed to navigate challenges in islet xenotransplantation. To optimize the informed consent process, standardized terminology and making complex information accessible and tailored to individual patient needs are crucial. |
| Hawthorne | 2024 | Frontiers in Immunology | Review | Current regulatory frameworks are insufficient for clinical translation of xenotransplantation due to failure to require an informed consent protocol that incorporates communicative lifelong surveillance, reproductive restrictions, and limits on withdrawal, which are imperative for protecting both participants and public health. |
3.1. Community and Collective Consent
“Community consent” was discussed as crucial for ensuring public awareness of the unique risks and benefits of islet xenotransplantation [5]. Ellis and Korbutt refer to this public consent process as “deliberative democracy.” [6] Similar approaches utilizing direct public consultation were previously applied in Canada and New Zealand. While research risks are not shared equally by all citizens, involving the public in this process by properly educating citizens with the help of medical experts can make a meaningful impact on the advancement of this novel therapy. Utilizing technology, such as online video conferencing, may aid in addressing this topic through democratic public consultation, though Ellis and Korbutt also caution that, because of the expected benefit to society, “the community must also not allow cautiousness to set overly stringent justifications for clinical trials.” [6]
3.2. General Recommendations on Informed Consent
Included sources emphasized transparent consent and patient compliance with standards to minimize risk [7]. Goerlich et al. recommend that a system for the surveillance of xenotransplantation‐related infection be established and acknowledge that the World Health Organization (WHO) has published guidelines advocating for the screening of xenotransplantation recipients and casual and sexual contacts [8]. Hawthorne notes that research non‐participants and the community need to understand the serious implications of xenozoonosis [7]. De Jongh et al. note that patient desperation for a cure can challenge the validity of informed consent [9].
3.3. Empirical Studies on Patient Informational Needs
Only two empirical studies were located. Marckmann and Thiersch conducted interviews with seven T1D patients to understand their thoughts on a model informed consent document for islet xenotransplantation and the questions patients have to make an informed decision about xenotransplantation [10]. Most of the interviewees held a positive attitude toward islet xenotransplantation. Concerns were expressed about three areas: (i) slaughtering of animals, (ii) stigma, and (iii) potential risks and illnesses associated with the transplant. The authors concluded that these are important issues to consider during an informed consent process.
In the second empirical study by Kogel and colleagues, seven patients with T1D were provided a model informed consent form for an islet xenotransplantation clinical trial and asked about their informational needs prior to islet xenotransplantation [5]. The researchers “identified several requirements that are crucial for patients with T1DM in order to consider xenotransplantation as a potential treatment option: therapy‐related requirements, professional care and supervision, successful behavior and attitude management, improving quality of life, and managing control/self‐determination challenges.” [5] Participants viewed xenotransplantation as a last resort option in the case that standard therapies failed. Regarding the model informed consent form, participants wanted additional details about a range of topics, including family planning, alternative therapies, data from previous studies, life expectancy of cells, risks, insurance coverage, and everyday life restrictions.
3.4. Patients Lacking Decision‐Making Capacity
Very little literature addressed pediatric patients or other individuals who are unable to provide informed consent. One commentary noted that for patients unable to consent, the legal framework is decided nationally [11]. Rood and Cooper found the inclusion of minors “highly controversial,” questioning the fairness of imposing potential lifelong burdens on those unable to provide full legal consent [12].
4. Discussion
While islet xenotransplantation is progressing, the ethical framework for informed consent is underdeveloped and lacks specific guidance. A critical ethical distinction exists between solid organ and islet xenotransplantation regarding the proportionality of risk and benefit. While informed consent for solid organ xenotransplantation is well‐addressed—often in the context of life‐saving interventions for end‐stage organ failure—it is unclear that a similar depth of work exists for islet xenotransplantation. Unlike life‐saving solid organ transplants, T1D is a chronic condition with established alternatives, such as lifelong insulin therapy or islet allotransplantation. The major benefit of islet xenotransplantation is its potential as a functional cure, yet the existence of these alternatives changes the ethical weight of the procedure's risks, such as xenozoonosis. Despite the availability of other treatments, patient desperation for a cure can still challenge the validity of informed consent, particularly as patients may only view xenotransplantation as a “last resort” when standard therapies fail. It is important to note that perception of a given novel therapy, such as xenotransplantation, may be shaped by the quality of information provided to patients.
Several gaps were identified. First, there is a lack of patient input. Only two small empirical studies (14 patients total) assessed patients’ informational needs. This fails to meet the principle of public involvement advocated by the WHO in the Changsha Communiqué [13]. Second, there is almost no guidance for pediatric patients. T1D frequently affects minors, yet this review found no literature addressing adolescent assent and only one commentary questioning the ethics of imposing long‐term surveillance burdens on children. There has been some consideration of this for solid organ xenotransplantation, especially for children with congenital heart disease for whom cardiac xenotransplantation may be therapeutic [14, 15], but there is very little on this for islet xenotransplantation. It may be time for the field of islet xenotransplantation to focus on developing specific ethical and procedural frameworks for pediatric participants. Third, the ethical and practical consent requirements for close contacts (family, sexual partners) are undefined [16]. These individuals face risks from potential xenozoonosis, yet their informational and consent/assent needs have not been adequately explored. Empirical studies are needed, and clear evidence‐based recommendations grounded in current scientific understanding may then be developed.
5. Conclusion
Islet xenotransplantation is progressing, yet without concurrent ethical readiness, particularly in the form of informed consent, this progress risks undermining patient trust and public safety. This review has highlighted a scarcity of scholarly discourse and published guidance on informed consent specifically in the context of islet xenotransplantation. We invite others in the xenotransplantation community to aid these efforts.
Author Contributions
Daniel J. Hurst conceived of and oversaw the review. Jennifer Kovalcik, Sheetal Mohanty, and Mairead Higgins contributed to running the search strings and manually extracting sources into the reference manager system Zotero. Jennifer Kovalcik and Sheetal Mohanty screened the full texts of articles. All authors contributed to the drafting of the article and approved the submitted version.
Funding
The authors have nothing to report.
Ethics Statements
DJH is Chair of the International Xenotransplantation Ethics Committee. The viewpoints expressed here are his own.
Acknowledgments
The authors have nothing to report.
References
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