Alliances, collaborations and consortia: the International Stem Cell Forum and its role in shaping global governance and policy

Efforts directed at addressing the challenges posed by globalization are flourishing, particularly with respect to the ongoing need for governance and policy interoperability. While heterogeneity of national policies governing stem cell research at all its stages (collection, derivation, use, storage and distribution) still remain within and between jurisdictions, the globalization of the stem cell field has, somewhat paradoxically, contributed to the convergence of normative and scientific standards, as well as governance and ethical principles (Figure 1)[1]. As a vast range of pluripotent stem cell lines are continuously immortalized, transformed and distributed across jurisdictions; so are policy goals, models and mechanisms for implementation, which are mobilized across the globe in space and time [2] by the work of scientific alliances, networks and other institutions.

This article provides a succinct review of the International Stem Cell Forum (ISCF), the first transjurisdictional organization of funders of stem cell research [102]. It examines three ISCF initiatives as examples of how international consortia can help shape global governance and scientific practice.

Alliances, collaborations & consortia & the shaping of global governance and policy

Policy transfer is conducted by a range of national, international and regional actors in a multidisciplinary and multidimensional manner [3,4]. Notable examples are: the International Society for Stem Cell Research (ISSCR) [103], the ISCF [102] together with the International Consortium of Stem Cell Networks [5], as well as the Inter-State Alliance on Stem Cell Research [6], the EU [104] and finally, the Organization for Economic Co-operation and Development [105]. By asserting legitimacy pressures, these ‘policy agents’ serve as mediators of crossjurisdictional policy transfer and innovation by promoting transnational governance [4] while simultaneously urging jurisdictions to engage in normative action. The power of these institutions in fostering scientific progress by promoting best practices and policy innovation should not be underestimated. Given that socio–cultural, historical and political contexts greatly shape both the debates and policy outcomes, best practices developed by these actors are also promoting prospective policy evaluation, as they in turn build on the knowledge and experience of other institutions and jurisdictions in developing and implementing policy frameworks [7].

Professional organizations, such as the ISSCR [103], provide an institutional foundation for the development and dissemination of best practices. ISSCR has been fostering global governance and international cooperation in stem cell research and clinical translation since its inception [106] through the adoption of guidelines seeking to promote responsible, transparent and uniform practices worldwide [107]. Furthermore, a global governance and educational tool was promoted with ISSCR’s initiative ‘A Closer Look at Stem Cell Treatments’ [105], which targeted the complex problem of unproven stem cell interventions marketed around the world (‘stem cell tourism’). Additionally, a global, prospective and ethical framework has also been promoted by the Canadian Stem Cell Foundation, which in 2009 launched the ‘Stem Cell Charter’ [8]. Founded on the values guiding the protection of human rights, the Charter articulates five principles advocating responsible stem cell science. These principles are:

• ▪ Responsibility to maintain the highest level of scientific quality, safety and ethical probity;

• ▪ Protection of citizens from harm and the safeguarding of the public trust and values;

• ▪ Intellectual Freedom to exchange ideas in the spirit of international collaboration;

• ▪ Transparency through the disclosure of results and of possible conflicts of interest;

• ▪ Integrity in the promotion and advancement of stem cell research and therapy for the betterment of the welfare of all human beings.

International cooperation and transnational education are also the remit of the International Consortium of Stem Cell Networks [5]. Their innovative approach seeks to expand “the concept of national research networks to the international level” with a series of knowledge transfer activities fostering the exchange of best practices [5].

As with other actors, professional organizations employ the power of persuasion as their main tool with regards to policy transfer, given that their authority for enforcement and accountability, including their capacity to impose sanctions, is virtually absent. In fact, despite the globalization phenomena, governance remains almost entirely the role of national authorities [9]. Funding organizations have an essential role to play in fostering international cooperation and promoting scientific integrity while accelerating scientific progress.

The ISCF

Once it was established that the true potential of stem cell research was improving scientific knowledge, as well as the ability to prevent and treat disease, the realization that this could only be achieved through the promotion of international collaboration and funding support led to the launch of the ISCF [102]. The ISCF was established in 2003 under the auspices of the UK Medical Research Council, and was comprised of 21 funding organizations of stem cell research around the world, with the overall objective to promote global good practice.

Areas identified by ISCF members where joint work would be particularly beneficial:

• ▪ Encouraging collaborative research across nations, boundaries and disciplines;

• ▪ Promoting sharing of resources and data, including cell lines, scientific protocols and guidance documents;

• ▪ Fostering training for researchers worldwide in the handling, growing and expansion of human stem cell lines;

• ▪ Identifying key research gaps and addressing them by capitalizing on national strengths;

• ▪ Facilitating transnational collaborations via funding schemes;

• ▪ Considering issues relating to the management of intellectual property in stem cell research and development;

• ▪ Analyzing ethical issues in stem cell research.

To achieve its objectives the ISCF supports three major international initiatives.

The ISCF Ethics Working Party (EWP) is an independent body mandated to review fundamental ethical policies pertaining to stem cell research. The EWP recognizes the complexities of the stem cell field, which is characterized by a vast range of pluripotent stem cell research and potential therapies, which are performed in a context of political and cultural diversity [108]. The ISCF-EWP aims to identify the different national ethical–legal and policy landscapes [10], in order to facilitate international dialogue on fundamental ethical issues, and to foster shared ethical principles so as to guide the conduct of stem cell research and policy making. As the ISCF-EWP fulfills this mission, via monitoring, horizon scanning and analyzing ethical issues and policy frameworks regarding stem cell research and stem cell-based therapies, the EWP continues to prospectively identify issues that are in need of ethical deliberation and further policy guidance.

The ISCF-EWP work program is designed to be prospective and responsive to the dynamic nature of policy and regulatory environments, as well as the rapid pace of scientific developments. As such, it has focused on analyzing substantive requirements and procedural safeguards in the regulation of stem cell research [11], the use of monetary payments for the procurement of oocytes for stem cell research [12], as well as ethical and regulatory issues surrounding stem cell banking [13]. Moreover, the EWP’s seminal policy statements on the managing of genetic data [14] and the disclosure research results and incidental findings in the context of stem cell research and banking [15] continues to inform scientific practice.

The International Stem Cell Banking Initiative (ISCBI) has been established with the vision of creating a global, interoperable network of stem cell banks, working jointly towards indentifying and harmonizing best practices for banking, characterization and testing of pluripotent stem cell lines [16]. ISCBI’s vision and mission is “to create a solid scientific and ethical framework for international stem cell banking and research” [17]. Important harmonization and standardization work has been carried out by ISCBI. In 2008, ISCBI adopted its first best practices: the ‘Consensus Guidance for Banking and Supply of Human Embryonic Stem Cell Lines for Research Purposes’ [18]. This guidance document seeks to be comprehensive in managing a wide range of aspects involved in a bioresource: from procurement to ethical provenance, governance, banking procedures, quality control, safety testing and international distribution. A set of best practices for clinical-grade pluripotent stem cell lines is currently being developed by ISCBI. The new guidelines will establish an international set of standards for stem cell lines destined to be used in clinical translation as well as clinical trials, and will cover procurement, characterization, testing, maintenance and shipment. It is envisaged that ISCBI will have an important role to play in shaping research and its clinical translation by creating the foundations for stem cell banking [17].

The International Stem Cell Initiative (ISCI) recognizes the importance of scientific consortia in high-quality scientific practice by promoting standardization. The ISCI was created in 2004 with the view of establishing criteria and techniques to support the development and use of human embryonic stem cell lines for medical applications [19]. ISCI groundwork is divided into three initiatives: the ISCI-1 main objective was to systematically define key features of human embryonic stem cells (hESCs) and to establish whether or not hESCs share common features. The ISCI-1 enlisted the work of 17 laboratories (spanning 11 different countries) to analyze 59 independent hESCs and established a globally agreed upon set of criteria for characterizing stem cell lines [20]. ISCI-1 identified “a set of standard markers that could be used to characterize and monitor the behavior of hESCs in future experiments” [109] and established the ISCI Registry [110], which published the results of the work carried out by ISCI projects. This was followed by ISCI-2, which was charged to compare the performance of different media for the culture of hESCs and to study the genetic changes that can occur in hESCs on prolonged passages in culture [21]. Finally, ISCI-3 is entrusted to establish a consensus on quantifiable protocols that can be used to assess the capacity of individual pluripotent stem cell lines (ES or iPS) to differentiate along specific lineages [22].

Conclusion

Foresight and global approach to scientific innovation are two characteristics of major national and transnational stem cell initiatives, alliances, networks and institutions. Indeed, the ‘globalization’ of the stem cell field has shifted the sphere of debate and action from national to the international [23]. Despite the strengthening of international consortia seeking to accelerate scientific progress by promoting collaboration via the sharing of resources and the establishment of best practices, an effective global governance framework is yet to be consolidated. The latter is reflected in the challenges ensuing from the controversial phenomenon of stem cell tourism [24]. Funding consortia, such as the ISCF, have a major role to play as agents both for policy transfer and global governance.