Lancet Commission: Stem cells and regenerative medicine
In this Commission, we argue that a combination of poor quality science, unclear funding models, unrealistic hopes, and unscrupulous private clinics threatens regenerative medicine's social licence to operate. If regenerative medicine is to shift from mostly small-scale bespoke experimental interventions into routine clinical practice, substantial rethinking of the social contract that supports such research and clinical practice in the public arena will be required. For decades, stem cell therapy was predominantly limited to bone marrow transplantation for haematological diseases and epidermis transplantation for large burns. Tissue engineering and gene therapy faced huge challenges on their way to clinical translation—a situation that began to change only at the end of the 1990s. The past 10 years have seen an exponential growth in experimental therapies, broadly defined as regenerative medicine, entering the clinical arena. Results vary from unequivocal clinical efficacy for previously incurable and devastating diseases to (more frequently) a modest or null effect. The reasons for these widely different outcomes are starting to emerge. At this stage in their evolution, these experimental therapies (which include, but are not limited to, cell and gene therapy, tissue engineering, and new generation drugs) are necessarily financially expensive. Rigorous and costly clinical-grade procedures have to be followed in the development of medicinal products (involving cells, genetically manipulated cells, viral vectors, or biomaterials with or without cells), often produced in a very limited run. The cost of developing sufficiently high-quality trials means that only wealthier countries are able to fund them. Although public investments in this field are massive internationally, they do not carry guaranteed commercial returns. Compared with conventional drug development, such products follow a highly uncertain route to market. Furthermore, new therapies expose patients to risks, some of which are difficult to predict even with inbuilt safeguards. Despite the relatively small number of clinical successes, optimism and excitement about the potential effect or implications of this field remain great. This enthusiasm has led to gaps between people's expectations that new therapies should be available, often inflated by media reports, and the realities of translating regenerative technologies into clinical practice. The same environment is also permissive of one-off compassionate applications and poorly regulated trials. Indeed, the number of poorly regulated clinics has grown; clinics that appeal to desperate patients and their families, who, in the absence of reliable clinical knowledge from trials, cannot be adequately informed to assess the risks and benefits. These ethical and governance issues pose a challenge to scientists in engaging with the public, the press, and decision-making bodies in different national health systems. Political agendas might not coincide with the public good. In poorly regulated states, the authorisation of a novel therapy might be politically attractive, even when efficacy is unconfirmed, and the cost to taxpayers means other patients are deprived of established and effective therapies. These challenges are difficult to address and solve. We recommend a solution that lies in a coordinated strategy with four pillars: better science, better funding models, better governance, and better public and patient engagement.