CEU’s CELAB Hosts Workshop on Ethical and Legal Challenges of Stem Cell Therapy

The Centre for Ethics and Law in Biomedicine (CELAB) hosted a two-day workshop on Stem Cells from Bench to Bed, from Procurement to Application: Ethical and Legal Challenges at CEU on May 18-19. The event was organized by Professor Judit Sandor, of the Departments of Gender Studies, Legal Studies, Political Science, and the Doctoral School of Political Science, Public Policy, and International Relations, and director of CELAB, Marton Varju, research associate at CELAB, and Jasper Bovenberg, research fellow at the Legal Pathways Institute for Health and Bio-Law, Netherlands, as part of the EUCelLEX 7th Framework Project. The workshop brought together scientists, lawyers and philosophers from a number of countries, including stakeholders in the EUCelLEX project. The focus of discussion was to identify the regulatory and legal issues that have arisen in light of recent breakthroughs in stem cell research.

The first session of the workshop was opened by Andras Dinnyes, director of BioTalentum Ltd.  Dinnyes presented research on the technological advances that have been made in developing patient specific induced pluripotent stem cells (iPSCs). The use of patient-derived iPSCs has three main advantages. Firstly, they allow for the modeling and investigation of diseases specific to the patient. Secondly, they provide a platform for investigation the specific drug reactions of the patient in vitro. Thirdly, they serve as an unlimited source of compatible cells for cell replacement therapies to treat degenerative diseases.

Dinnyes’ presentation was followed by a talk by Abdoelwaheb El Ghalbzouri, assistant professor at Leiden University and advisor at Biomimiq. Ghalbzouri spoke of current research on the tissue engineering of living cells to develop biological substitutes for skin tissue replacements. An example of this is human skin equivalents (HSEs). Ghalbzouri claimed that in vitro HSEs are able to capture most of the in vivo characteristics of human skin. The development and use of HSEs potentially has a number of benefits. In addition to generating skin tissue for therapeutic purposes, they provide a real alternative to the use of animal experimentation for identifying the safety of pharmacological and cosmetic ingredients. However, in order for HSEs to achieve these benefits, Ghalbzouri emphasized the need for further research on the development of in vitro systems modeling skin healing, skin ageing and specific skin diseases.

The final presentation of the first session was delivered by Anna Veiga, director of the Stem Cell Bank Centre for Regenerative Medicine in Barcelona. She summarized various models of regenerative medicine and contemporary European challenges.

Pro-Rector for Social Sciences and Humanities & Hungarian Affairs Laszlo Kontler speaks at stem cell workshop at CEU. Photo: Kinga Lakner

Session two was opened by Robert Vries, managing director of Hubrecht Organoid Technology Foundation and Living Biobank. Vries discussed research currently being carried out at the Hubrecht Organoid Technology Foundation (HUB) on organoid technology. An organoid is an in vitro culture system, derived from stem cells that allow for the genetically and phenotypically stable expansion of cells that faithfully represent in vivo cells.  HUB has generated a large collection of patient organoids from a variety of organs and diseases. In particular, their research has indicated that intestinal organoids are an invaluable tool for studying cancer, cystic fibrosis and inflammatory bowel disease. The specific benefits of the therapeutic use of organoids include their patient-specific application in drug-development and diagnosis.

Following Vries, Emilia Madarasz, member of the Hungarian Academy of Sciences, discussed the limitations of applying tissue stem cells as therapeutic tools. Contrary to previous speakers, Madarasz dramatically emphasized the lack of knowledge and research on the potential side effects and long-term ramifications of therapeutic stem cell use, particularly in the domain of neural regeneration.

The second session ended with a presentation by Istvan Szatmari, senior lecturer at the University of Debrecen, who described the promise of applying dendritic cells (DCs) in cancer immunotherapy. Two difficulties with the application of this research, however, were identified. The first difficulty is ethical: DCs are difficult to manufacture from adult stem cells and so research currently relies on the use of pluripotent embryonic stem cells (ESs). The second challenge is practical: the immaturity of ESs impairs their potential for immunogenicity.

Day two of the workshop focused more closely on the regulatory and legal issues of the procurement and use of stem cells. Session three began with a presentation from Judit Maria Molnar, vice rector of Semmelweis University, focusing on the moral implications of stem cell research. Molnar argued that iPSCs are too easily thought of as an ethically neutral alternative to the use of embryonic stem cells (ESCs). In fact, the use of iPSCs is not free from ethical questions. One ethical concern relates to privacy: iPSCs contain genetic information of the somatic cell donor which needs to be appropriately protected and managed. A second concern relates to permission: it is questionable whether researchers ought to be allowed to carry out research that uses iPSCs to derive germ cells or to grow human organs inside of animal bodies.

The second presentation of the session was delivered by Rosario Isasi, research associate at McGill University, who compared a number of international regulatory frameworks on regenerative medicine. Current regulatory challenges arise from the attempts of some jurisdictions to integrate emerging technologies into existing frameworks, originally designed for the regulation of pharmaceuticals and medical devices. Other jurisdictions have limited guidance, relying on case-by-case approaches. This is often seen as an advantage to researchers, allowing for accelerated licensing.  In view of this international variance, Isasi ended her talk by emphasizing the importance of international harmony in regulation.

The third and final presentation of the session was given by Balazs Sarkadi, head of the Membrane Biology Research Group at the Hungarian Academy of Sciences. He focused on the use of commercially available stem cell based medicinal products as regulated by the European Medicines Agency (EMA). The EMA takes a risk-based approach to regulation, but the development of new products requires regular updating of the guidelines. Sarkadi explained how the Committee for Advanced Therapies (CAT) based within the EMA is currently working on guidelines specifically relating to unapproved stem cell therapies and ‘stem cell tourism’.

The final session of the workshop continued with the theme of regulation and delivered further insights into current advances in the field.  Katalin Rajczy, director of the Hungarian Stem Cell Donor Registry and Hungarian National Blood Transfusion Service, began the session by speaking on the current challenges of the umbilical cord blood banking.

The session concluded with a presentation from Antal Nogradi, head of the Laboratory of Neural Regeneration at the University of Szeged, who spoke on the use of clonal stem cells in diseases of the nervous system. Nogradi illustrated that clonal stem cells have been found to produce significantly improved outcomes in the treatment of spinal cord injuries.

The workshop ended with a panel discussion on the regulation of stem cell research and regenerative medicine, led by Bovenberg, Sandor and Varju (working party of the EUCelLEX project). The panel noted that discussions throughout the workshop had shown that the potential benefits of stem cell research for therapeutic practice are vast, but that this is impeded by an ill-suited regulatory framework. In light of this, the panel recommended that current regulatory frameworks ought to be broadened, especially in relation to autologous (i.e. non patient-derived) cell therapies. Rather than revising current regulations, it was suggested that hospital exemptions ought to be extended in order to allow for easy access to routine preparations. Where this is not possible, the EU should consider promoting the free movement of patients to the available product – moving towards a safe stem cell therapy tourism. The following discussion emphasized that this recommendation is not without its caveats. Caution is still required, both in order to protect patient privacy and also in terms of forestalling the unknown risks of regenerative medicines.