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Stem Cell Reports
Stem Cell Reports
Stem Cell Reports
2213-6711
Elsevier

S2213-6711(24)00214-5
10.1016/j.stemcr.2024.07.006
Perspective
Dynamic governance: A new era for consent for stem cell research
Isasi Rosario risasi@miami.edu
1∗
Bentzen Heidi B. 2
Fabbri Morris 1
Fuhr Antonie 3
Glover Joel C. 4
Mah Nancy 3
Mascalzoni Deborah 5
Mueller Sabine 3
Seltmann Stefanie 3
Kurtz Andreas 3
1 Interdisciplinary Stem Cell Institute and Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, FL, USA
2 Centre for Medical Ethics, Faculty of Medicine, University of Oslo, Oslo, Norway and Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway
3 Fraunhofer Institute für Biomedizinische Technik (IBMT), Joseph-von-Fraunhofer Weg 1, 66280 Sulzbach, Germany
4 Department of Molecular Medicine, University of Oslo, and Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway
5 Centre for Research Ethics and Bioethics (CRB), Uppsala University, Uppsala, Sweden
∗ Corresponding author risasi@miami.edu
15 8 2024
10 9 2024
15 8 2024
19 9 12331241
© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Summary

Governance infrastructures streamline scientific and ethical provenance verification of human pluripotent stem cell (SC) lines. Yet, scientific developments (e.g., SC-derived embryo models, organoids) challenge research governance approaches to stored biospecimens, questioning the validity of informed consent (IC) models. Likewise, e-health platforms are driving major transformations in data processing, prompting a reappraisal of IC. Given these developments, participatory research platforms are identified as effective tools to promote longitudinal engagement, interactive decision-making, and dynamic governance. Learning from European initiatives piloting dynamic IC for biobanking and SC research, this Perspective explores the benefits and challenges of implementing dynamic IC and governance for SC.

Scientific developments (e.g., stem cell-based embryo models, organoids, and chimeras) and evolving e-health platforms are driving major transformations in research and data processing applications, challenging existing research governance and informed consent (IC) models. Participatory research platforms, including dynamic IC/governance systems, are emerging as effective tools to promote longitudinal engagement and interactive decision-making. Regional examples demonstrate the feasibility of such approaches.
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pmcIntroduction

Stem cells (SCs) have opened a new era for regenerative medicine by advancing cell therapies. SC research can leverage thousands of biosamples from which human pluripotent stem cell (hPSC) lines can be obtained, distributed, and processed over time, worldwide, for current and future uses unforeseeable at the time of donation, and under heterogeneous regulatory regimens. Accordingly, hPSCs are subject to iterative provenance assessments of intended uses against informed consent (IC) and legal-ethical regimen. With SC research advancing toward clinical translation, it is imperative to revisit the adequacy of traditional approaches to IC (Stacey et al., 2013). After all, it is the breadth and scope of the IC process that ultimately justifies the use and control of donated biosamples for SC derivation and downstream uses.

In this context, participatory research platforms have been heralded as effective tools to promote longitudinal engagement and support interactive decision-making. Participant empowerment warrants a change in terminology. Individuals who donate their biological material and/or data for research should no longer be referred to as “donors,” whose donation is a one-time interaction, but rather as “participants” with an active role in the fate of their biological samples and data (Lensink et al., 2022). We use the term “participant” in this broad sense. Sustained participation contributes to scientific utility and clinical safety while advancing participant interests (Isasi et al., 2011). For instance, it allows for reliable tracing of hPSC lines to the participant, permits ongoing collection of medical information, and facilitates correlating phenotypic and genotypic data with other biological characteristics from the resulting line, which is important for translational SC research and therapies (Isasi et al., 2011).

Building on existing governance strategies providing ongoing support for broad IC frameworks, and against the background of conventional (one-time) IC approaches, we explore the benefits and challenges of implementing dynamic IC models (DC) for SC research. Learning from regional examples piloting DC models for biobanking and SC research in Europe, we explore the linkage between DC and governance, arguing for a shift in focus from mere future use authorization to more interactive and robust participatory oversight of SC research and clinical translation.

Consent is used in this article to describe IC to research participation, a process responding to the requirement in the World Medical Association Declaration of Helsinki and other internationally accepted ethical guidance. This contrasts with IC as a lawful basis for data processing under national data protection laws, which may also involve DC (e.g., Articles 6 and 9 of the European Union General Data Protection Regulation 2016/679 [GDPR]).

The evolution of IC for SC research

The IC process operationalizes the principles of respect for dignity, integrity, and autonomy. This golden rule has been conceptualized and implemented differently over time (Stacey et al., 2013), as the complexities of research have progressed, and the role of research participants has been reexamined. As the field emerged with a predominantly embryo-centric approach, only a few jurisdictions enacted policies creating specific requirements for IC for SC research (Isasi and Knoppers, 2006). Overall, the general norms governing human subject research were extrapolated and adapted to capture the nuances of the field.

Early on, the International Society for Stem Cell Research and the International Stem Cell Banking Initiative (Andrews et al., 2015) pioneered best practices for prospective IC (ISSCR International Human Embryonic Stem Cell Research Task Force, 2007), outlining core elements to be disclosed during the IC process. While IC allowed participants to establish conditions for downstream uses, the process was conceptualized as a one-time engagement that ended once the biosamples were donated or the hPSC line was derived, and it relied on anonymization as an expedient way to allow for a waiver of IC while safeguarding participant privacy (Isasi et al., 2011). These practices represent the “broad” IC model.

Recognizing the ethical and legal distinctions between IC for research participation (as exemplified in the Declaration of Helsinki) and IC for data processing, the “tiered” IC model emerged. This model enhances participant agency, allowing for setting granular limits on the distribution of biosamples or hPSCs, the scope of downstream research uses, and/or the sharing of personal information (e.g., genetic or health-related data). It also provides an opportunity to exercise active choice regarding applications that could be deemed controversial (e.g., somatic cell nuclear transfer, creation of gametes/embryos, and SC embryo models).

In theory, the tiered IC model was designed for participants to articulate their preferences, and thus, to regulate the future use of their samples, rather than assigning that task solely to ethics oversight or access committees. However, the applicability of this model suffered because modern SC research projects can entail international, public-private partnerships that may be too nuanced to capture on a static IC form (Aalto-Setala et al., 2009; Budin-Ljosne et al., 2017; D'Abramo et al., 2015). Without sustained participant engagement, the model does not resolve the challenge of parsing participants’ intentions in the absence of their continued input. The operational costs associated with tracking, adhering to varied preferences (Grady et al., 2015), and attesting provenance make these options impractical, particularly given that the hPSCs may be shared and deposited across institutions globally. These challenges might explain why tiered IC has not been widely adopted within the SC field.

Borrowing from IC models successfully developed for biobanking, the SC field embraced the broad IC model, in which participants authorize a range of projects categorized by purpose, methodology, or other general criteria, without requiring specific IC for each use. Rather than learning the details of individual studies, participants agree to the “rules of the game” (Kaye et al., 2015), encompassing a more general account of risks and benefits.

Driven by an interest in exploiting large collections of biomaterials and data to maximum benefit, often supported by established biobanks (O'Shea and Abranches, 2020), broad IC has been deemed valid by current standards designed to promote scientific progress while protecting participants’ interests (Grady et al., 2015; Hallinan, 2020). Broad IC obtained in a discrete interaction prior to the research being carried out may ultimately benefit participants who prefer this mode of interaction, maximizing altruistic contributions to research without the need for—or burden of—ongoing engagement.

This approach is designed to mitigate the considerable administrative burden that accompanies the use of tiered IC. Instead, access to participants’ samples and information is mediated by oversight bodies or access committees, tasked to ensure that sample usage is consistent with participants’ IC, ethical principles, and national legal requirements (Beskow and Dean, 2008). In theory, this arrangement sets stable access conditions for researchers without diminishing the participants’ presumed interests and awareness of risks and benefits. Yet, some skeptics have questioned whether broad IC represents an impermissible compromise of participant autonomy in favor of research interests (Caulfield and Kaye, 2009). Still others argue that a robust IC should aim to achieve a cautious balance, limiting the pursuit of research in order to respect individual rights (Caulfield et al., 2007).

Scientific developments have changed research on stored biospecimens and hPSCs. While the advance of governance mechanisms has streamlined provenance verification (Isasi et al., 2019; UK Stem Cell Bank, 2010), the validity of previously obtained IC is questionable. For instance, scientific advances have facilitated the creation of increasingly sophisticated SC-derived embryo models, organoids, human-animal chimeras, and even synthetic embryos (Caulfield et al., 2009). Researchers conceivably did not anticipate such uses at the time of obtaining IC (Beskow and Dean, 2008), so it is unlikely that past IC interactions fully capture the depth and breadth of ethical concerns raised by these new and emerging techniques, which may conflict with participants’ values.

In addition, powerful data processing capabilities have led to the proliferation of personal data across clinical, research, and consumer domains. Cheaper genomic sequencing and analysis techniques result in even more data. These trends increase the likelihood that information with clinical significance can be linked to donors. Longitudinal participant data collection generated at different stages (e.g., during donation, usage, and/or processing) can be used for verifying and qualifying disease models in relation to late-onset phenotypes, thereby allowing participants to potentially benefit from the analysis of subsequently obtained data, as it could lead to the development of beneficial medical interventions, including cell therapies. Moreover, the safety and efficacy of allogeneic cell therapy may be impeded by the discovery of participant or biospecimen phenotypes unforeseen at the time of donation. However, these developments together with the fact that DNA can be generated from hPSC lines, which are self-renewable and can be distributed on a massive scale, might weaken promised privacy protections (e.g., against participant re-identification) by rendering the removal of direct identifiers ineffective (Knoppers and Isasi, 2010).

Digital modes of data collection, organization, and processing are dwarfing the capacity of traditional paper-based methods while streamlining access to participant-specific records and research results. Digital communication and record-keeping are drastically reducing the effort needed to re-connect with participants. Proponents argue that investment in digital infrastructure for ongoing engagement raises participants’ familiarity with research and teaches institutions how to better align their research with participants’ expectations (Ball et al., 2014).

The expectations of participants and patient communities have progressed as well, seeking a more active role in research by shaping its agenda, developing new approaches to IC, and empowering participants to direct downstream use (MacDuffie et al., 2023). The internet has opened new channels of communication making it feasible and, perhaps, desirable for participants to exert a more active, sustained influence over the fate of donated samples (Anderson et al., 2012; Pattaro et al., 2015).

In the following section, we review the benefits and challenges of implementing DC for SC research. As of now, there are no global policies, ethical standards, or default models for implementing such a model. Thus, in lieu of a “gold” standard, we reference key facets of early DC experiments in the general biomedical research domain. We also reference the evaluation and reporting framework proposed by Prictor (Prictor et al., 2018). We further present regional examples piloting DC models for biobanking and SC research in Europe (e.g., Norway and Italy) and explore the link between DC and governance.

A novel approach: DC

The DC model is grounded in individual autonomy (Kaye et al., 2015) and construed as an active partnership, which enhances decision-making (Prictor et al., 2018) throughout a research project’s lifetime. DC in its most efficient form uses digital tools (Prictor et al., 2020) with online communication platforms enabling participant’s involvement to match their changing preferences. DC can build on existing governance strategies and biobanking initiatives, providing ongoing support for an established broad IC framework. DC allows researchers—during the initial recruitment interaction—to present simple information about research participation, offering additional details as needed, and informing participants that they can adjust the accessibility of samples and associated data based on the latest information about research usage, and opt in–or out—of receiving individual and aggregated data and research results.

Throughout the course of SC research, biobanks, registries, and secondary research institutions collaborate to maintain a link between participants’ IC preferences, the hPSCs derived from them, and data generated from the characterization and downstream applications of the hPSCs. Implementing DC in the SC field can bolster existing systems of traceability and accountability by ensuring participants’ contemporary preferences are respected. Importantly, DC platforms could operationalize tracking systems for safety issues in clinical trials, such as the chain of hPSC custody, hPSC-related data, and accompanying participant information. Furthermore, ongoing engagement would allow participants to answer surveys on new research questions, supplementing hPSC characterization with new phenotypic information (e.g., patient-reported outcome tools to gain insight into phenotypic effects). Over time, researchers can also return clinically relevant or otherwise useful insights (e.g., genetic information on inherited disorders) gained from their research, and participants can indicate their receptiveness to results in real time.

Offering participants greater control might make participation more appealing. Newsletters and public media releases can complement direct participant communication by highlighting connections between participants’ contributions and the progress and impact of studies and clinical trials. Caution is advised, however, to avoid overemphasizing benefits, minimizing risks, or overselling the projects in a manner that could compromise IC (e.g., undue inducements). Moreover, recruitment and data collection efforts from myriad collaborators could generate a volume of communication that overwhelms participants. In the SC context, the challenges of coordinating participant engagement and evolving preferences are complicated by the frequency and geographic extent with which self-renewable hPSCs are distributed over time (Mascalzoni et al., 2022).

DC can improve ethical SC translation, yielding tangible societal benefits. By removing barriers to equitable research participation, DC may improve the diversity of samples and health data available. This can be accomplished, for instance, by removing geographic hurdles brought by cumbersome trips to research locations entailed by in-person models of IC or by increasing uptake of would-be participants who reject a broad IC model. Increasing participant-researcher communication may also generate a more scientifically literate population (Kaye et al., 2015) capable of dispelling some of the hype and misinformation that shrouds SC research.

Importantly, DC may improve public trust in that SC research becomes more transparent. Despite the rapid progress of the field, most national SC policies have not been substantially revised in the last decade, contributing to concerns about whether rules and enforcement mechanisms in place are still sufficient to safeguard public interests (Isasi et al., 2022). While professional societies have encouraged public conversations to clarify societal support for new and potentially controversial forms of research, these conversations have yet to materialize on a large scale (Adashi and Cohen, 2022). In theory, DC platforms would allow participants to respond more directly to research that conflicts with their values. At the same time, centralized online communication hubs can be used to issue surveys and track decision-making trends regarding contentious projects, such as the public outreach communication projects EuroStemCell (EuroStemCell) and EuroGCT (EuroGCT). Over time, DC may yield insights into the project features that participants find most meaningful, which could then be incorporated by researchers and oversight bodies who critically examine ethical justifications for future hPSC uses. Empowering participants to check controversial research may thus instill confidence that progress in SC research and translation proceeds on broadly acceptable terms.

DC addresses flaws associated with current IC research practices, yet challenges remain. Just as DC builds on previously established IC norms, it also inherits a lack of standard metrics to evaluate its various components. Although trials have demonstrated the feasibility of implementing online platforms to supplement IC, it is hard to measure their relative success or failure, and to evaluate how they can be extrapolated to the SC field (Prictor et al., 2020).

Uncertainty surrounding the effectiveness of DC is just one of the questions confronting oversight bodies. An important issue is the effect of digital interaction. As the forum for meaningful decision-making moves from the physical into the virtual realm, researchers may lose insight into, and thus, control over, the quality of participants’ decision-making. During an in-person interaction (even over the phone), researchers can usually gauge whether participants have attained the baseline level of comprehension necessary for IC. Using online portals, however, it may not always be clear whether people are who they say they are, are competent to give IC, or are free of undue influence. Moreover, in-person interviews purportedly meet ethical and legal thresholds because they offer substantial opportunity to ask questions and weigh options before enrolling in a study. This could be achieved in digital platforms by adopting appropriate evaluation methods and frequently asked questions. More evidence is needed to evaluate whether the interactions enabled by online platforms—whether through video, audio, or text—can live up to the in-person standard.

DC governance also needs to focus on the format of participants’ identity encryption because globally distributed hPSCs are usually anonymized, eliminating the possibility of participant re-contact. Anonymized hPSCs cannot be re-transferred into a DC process, but it would be feasible for pseudonymized (i.e., key coded) hPSCs. In this case, the institution that collects and manages the original source cell material, holding the key linking the participant to the end material to be used, can contact the participant using a strict governance process to implement the DC model. Alternatively, a new globally active institution could be set up that controls access and guarantees the management of the key and the re-contact process. For new biospecimen donations, the possibility of DC should be considered immediately, and if a participant decides to use this model, attention must be paid to the correct type of data encryption. Globally, researchers would need to quickly identify whether the hPSCs they plan to use were donated under a DC model and how to implement it. Databases such as the hPSC registry (hPSCreg) (hPSCreg; Kurtz et al., 2022; Seltmann et al., 2016) can provide information about this in their public registries and establish the link to the administrative body that has the means to re-contact the participant. Via these publicly available databases, the end user can determine whether the desired hPSCs require DC governance (Figure 1).Figure 1 Dynamic governance process

Despite these feasible solutions, DC brings logistical hurdles associated with the creation and maintenance of secure and sustainable online portals to track participants’ preferences and coordinate communication with researchers. For instance, operationalizing the right to withdraw would be a major challenge. This is because under the currently dominant commodity model based on broad IC, once hPSCs are derived, the hPSCs and associated data might no longer be under participants’ control, but under the control of the deriving institution (Council of Europe, 2008). While material transfer agreements (MTAs) require that secondary research complies with the terms of IC, MTAs are typically unidirectional, effectively muting participants, who no longer have active control over the fate of the hPSC lines derived from donated biospecimens. Certainly, the commodity model creates a dichotomy between donation and commodification by turning altruistic donations into technological tools, which can be handled as a “commodity” (Boers et al., 2019). Weighed against the disruption DC may pose for existing material and intellectual property arrangements, the case for expanding participants’ authority over SC lines rests on two related and unsettled assumptions: that participants retain a right to control biomaterials from which their DNA can be generated and that participants have strong interests in maintaining a connection to hPSC lines derived from donated biosamples. While a more abstract philosophical analysis is beyond the scope of our paper, this dilemma is embedded within a broader distinction between autonomy and authority, and the issue of whether IC is about respecting decisions or the people who make them (Johnsson and Eriksson, 2016).

Implementing DC for SC research

Thus far, DC projects have been limited to individual institutions (Thiel et al., 2015) or small geographic regions (Mascalzoni et al., 2022), leveraging pre-existing connections with participants, communities, and other stakeholders to craft IC platforms that satisfy their needs. Yet important regional examples piloting DC models for biobanking and SC research in Europe are emerging (e.g., Norway and Italy). Above all, the production of hPSCs from somatic cell material that is already donated regionally in biobanks (e.g., cord blood, skin fibroblasts, and bone marrow) is becoming increasingly attractive for research. At the regional level, there are many approaches and initiatives to re-contact donors of somatic cell material to obtain IC to derive hPSCs from their materials. In the following section, we provide an overview of two of such initiatives.

The Norwegian induced pluripotent stem cell biobank for clinical applications

With the establishment of Norway’s national biobank of hPSCs for clinical applications, a new quasi-DC model was created to ensure that participants who donate biosamples that will be reprogrammed to hPSCs would have the opportunity to (1) request, at any future time, information about the use of their donated materials, (2) provide IC to be re-contacted should the future use of hPSCs encompass uses not foreseen at the time of the original IC, (3) provide IC for the return of results should analyses of the hPSCs reveal clinically actionable genetic information (e.g., conditions with clear medical consequences that should be addressed), and (4) withdraw IC at any future time, being informed of potential limits of the withdrawal (e.g., if data have already been used and shared).

The Norwegian model does not encompass all features of the ideal DC model. It is not digital (i.e., enrollment and IC are not obtained through an online system) and does not provide a continuously interactive process whereby participants can follow and control the future use of hPSCs in real time. Still, it goes far beyond the normal “one-off” IC models typically used for cell donations in Norway (e.g., bone marrow donations), combining features of tiered IC and some features of an ideal DC (Figure 1). Moreover, several conditions are implicit in this model, in keeping with current Norwegian laws and regulations governing cell therapeutics and GDPR. As these laws and regulations may change in the future, the platform provides a way to re-assess the IC should that situation occur, since participants can contact a designated participant communications office affiliated with the national biobank at any time, and vice versa. Compliance with GDPR is guaranteed by setting up a two-tier system in which all participant contact is handled by the designated participant communications office, which establishes a pseudonymized coding of the donated biosamples, and stores the coded personal information separately (with no physical or net-based connection) from the biobank itself and its managers. This intervening relay thus restricts access to non-pseudonymized information to the designated participant communications office, which is separate from the biobank.

The Norwegian government is piloting another DC model related to biobank research (Det Kongelige Helse-og Omsorgsdepartement, 2022) to assess whether a joint technological platform can be set up for such purposes across Norway. The already existing HelseNorge (HealthNorway) website (Helsenorge) is being considered as a portal for citizens to be provided with an overview of and the ability to administer all their ICs, a solution one of us suggested in 2015 (Budin-Ljosne et al., 2015). It will be interesting to see if IC management can effectively be implemented at this national scale for the benefit of all stakeholders (Budin-Ljosne et al., 2015).

The Eurac Research for the Italian Cooperative Health Research in South Tyrol Cohort

Cooperative Health Research in South Tyrol (CHRIS) is a longitudinal study in Northern Italy that since its inception in 2011 has used DC to enable the sustainable use and re-use of data and biosamples in line with high ethical and legal standards (https://chrisportal.eurac.edu/chris-study). CHRIS’s DC model provides an interactive process based on robust governance and an ongoing tailored communication with participants. It aims to promote autonomy and to develop a trust-based relationship with participants (Mascalzoni et al., 2022). Built within an online platform, the IC allows granular choices, which can be changed over time (Biasiotto et al., 2021; Pattaro et al., 2015).

The CHRIS DC ensures that participants are informed in depth about the study’s policies regarding the use of biosamples and data, and about their re-use, by providing details that cannot be conveyed at the time of the donation or collection. Participants can opt out of projects they do not want to contribute to, or opt in in case new projects are proposed (e.g., COVID studies). The IC is broad regarding research areas, but specific about the rights of participants and transparent regarding the project’s governance. Participants can give nuanced permissions concerning use and re-use of biosamples and data by expressing whether they allow sharing within Europe or worldwide. They can choose whether and how they want to be re-contacted for return of results, should research reveal genetic conditions that fall within the return policy. They can withdraw their IC at any time and are informed about the potential limits of the withdrawal (e.g., if data have already been used and shared). Importantly, CHRIS provides a process of co-production with a high degree of participant engagement, in which their views are consulted and inform project development over time (Biasiotto et al., 2021; Pattaro et al., 2015).

The CHRIS platform is partially digital. IC is obtained face-to-face at the first visit using the online platform with the assistance of researchers. Participants acknowledge the right to use the platform to change their IC options but can opt to do so in writing if they do not wish to use the platform. Communication is an essential part of the IC process through in-person interactions, or the use of the platform’s app. Communication is based on language-tailored multimedia (e.g., brochure, webpage, resume, movie/interactive presentation, and study updates) and continuous (e.g., materials at home, interactive presentation at the study center, and future information online or via letter). These tailored materials visualize complex concepts and convey them more readily than mere written descriptions.

Furthermore, in Europe, there are already pilot projects working to implement GDPR-compliant technical platforms for DC, following the GDPR requirements that research participants must be informed of any novel data processing that is not covered in the original data collection, and that they have the right to withdraw their IC (GDPR Art. 13(3), Art. 7). An example of this is Integration of Heterogeneous Data and Evidence toward Regulatory and HTA Acceptance, a European public-private partnership launched in April 2023 “to build a scalable platform for a seamless integration or linkage of diverse real-world data at scale to support healthcare professionals, patients, and researchers with new capabilities to improve patients’ outcomes” (IDERHA). These platforms will become essential to support participants’ autonomy in the face of major developments to encourage the reuse of data from publicly funded research projects, clinical trials, and from the secondary reuse of health data (European Commission Directorate-General for Health and Food Safety).

The aforementioned scientific and technical developments question the ability of static IC models to address the uncertainties related to future SC applications. The cited regional examples of implementing DC are flexible models that can accommodate participants’ and researchers’ needs and meet ethical and legal standards while addressing technical implementation challenges.

Conclusion: Dynamic governance for SC research – A surmountable challenge?

IC is not an “ethics-clearing” exercise (European Commission Directorate-General for Research Innovation), but a partnership through which participants and researchers can build shared understanding to navigate scientific and ethical frontiers. The complexities of the SC field together with the wide spectrum of participants’—and other stakeholders’—interests, expectations, and values can best be captured by a system that enables heightened governance. DC entails a system that effectively supports dynamic governance (DG) (Boers and Bredenoord, 2018). Such a system departs from the traditional sole focus on the breadth and scope of future use authorization, to one centered on the conditions for robust oversight. As proposed by Boers and Bredenoord, the latter can only be achieved through the implementation of IC for governance, a model that shifts “the ethical emphasis from initial consent to ongoing governance obligations,” such as participant privacy safeguards, tools for participant engagement, benefit-sharing, and ethical oversight (Boers and Bredenoord, 2018).

DG for SC research is needed to ensure that the basic tenets of IC are upheld in the face of technological advances that enable unforeseeable research applications. DG can integrate guidance from existing IC models and by biobanking structures, such as organ or bone marrow transplantation, or cord blood donation as well as from existing SC banks. However, it will necessitate new components to adequately cover unforeseen research and therapeutic applications as well as participant risks (e.g., data privacy breaches) as the result of future research. With the recent policy changes toward the establishment of national health data frameworks to digitize health data (European Economic and Social Committee, 2022; Expert Advisory Group, 2022), patients are empowered to take a proactive role in their own healthcare, using electronic health records and health apps. This development has implications for the secondary usage of clinical data and biosamples for research purposes, which can in principle be managed by participants themselves using the same digital infrastructure. The adoption of e-health platforms will drive major transformations in the ways in which we collect, store, process, and exchange data; inform and advise participants; and manage IC for data and biospecimens used in research. This in turn offers opportunities for implementing DC in research settings. Health data and digital literacy together with trust in the platform are novel elements that need to be addressed. Educating individuals in using and understanding emerging technologies driving both digital infrastructures and biosamples processing/usage could further foster DC and DG.

The implementation of DC/DG for SC research is more likely to meet the expectations of all stakeholders if it can draw on a broad range of projects aimed at supporting public familiarity and engagement with science. Eventually, with enough funding, resolve from professional, academic, and patient communities, and small-scale proof-of-concept models, the DC model may expand and bolster a more informed and involved participant pool. However, fundamental operational considerations and challenges exist for the effective implementation of DC, such as allocating, defining, and shifting responsibilities, which require significant investment. As developments in SC research and clinical translation prompt reconsideration of whether current, long-standing policies remain fit for purpose (Lovell-Badge et al., 2021), it is timely to discuss how stakeholders weigh incentives and obligations when deciding whether to incorporate DC into the future of SC research.

Supplemental information

Document S1. Consent Templates: Norwegian IPSC Biobank for Clinical Applications (NIBCA)

Document S2. Article plus supplemental information

Acknowledgments

R.I.: European Union (EU) 10.13039/501100007601 Horizon 2020 (H2020) research and innovation program under grant agreement (GA) no. 825925 (IPSpine Project). A.K., D.M., H.B.B., and J.C.G.: the 10.13039/501100000921 European Cooperation in Science and Technology (COST)-Action Haplo-iPS CA21151. A.K.: EU Horizon Europe under GA no. 101074135 (hPSCreg). H.B.B.: EU GA 101071203 , 101006012 , and 101006430 and the 10.13039/501100005416 Research Council of Norway project number 322672 . D.M.: Department of Innovation, Research and University of the Autonomous Province of Bolzano-South Tyrol.

Author contributions

R.I. and M.F. conceived the original idea and developed the original draft. H.B.B., A.F., J.C.G., N.M., D.M., S.M., S.S., and A.K. proposed a structure and content. H.B.B., D.M., and J.C.G. drafted the case studies. All authors contributed to the writing of all sections and provided intellectual contribution per ICMJE guidelines. R.I. led manuscript finalization. All authors have read and approved the final manuscript for publication.

Declaration of interests

The authors declare no competing interests.

Supplemental information can be found online at https://doi.org/10.1016/j.stemcr.2024.07.006.
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Det Kongelige Helse- og Omsorgsdepartement Tildelingsbrev Til Direktoratet for E-Helse for 2022 2022
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EuroStemCell. EuroStemCell is here to help European citizens make sense of stem cells. https://www.eurostemcell.org.
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UK Stem Cell Bank Code of Practice for the Use of Human Stem Cell Lines 2010 Version 5
