The Stem Cell Market and Policy Options: A Call for Clarity

The field of regenerative medicine is widely viewed as having the potential to improve treatment options for a broad range of conditions. Stem cell research in particular has been celebrated for its considerable clinical promise. Although measured enthusiasm surrounding this area of research is warranted, it must be balanced by patience and set in the context of a long-term perspective that is cognizant of the many steps required to bring safe and efficacious therapies to market. Creating therapeutic applications of stem cell technologies is an intricate process involving complex biology. It will require careful scientific investigation and evaluation under responsible ethical frameworks and regulatory standards in order to safely maximize their potential. Alongside the many promising avenues of responsible research currently underway in countries throughout the world, a global market has emerged where a wide range of putative stem cell-based interventions are sold on a direct-to-consumer basis and marketed over the internet.1,2,3,4 In this paper, we discuss a number of concerns associated with this market that stem from a lack of clarity in several key areas, and propose approaches for how they might be remedied. Although we are not the first to identify many of these concerns, their persistence demonstrates the need for clear and concise actions. The market for unproven stem cell-based interventions engages varied interests and crosses different regulatory, research, and clinical domains. We draw on the considerable body of work in this area to highlight the contributing factors to this problem and to facilitate actions to ameliorate some of the most concerning issues. Engaging the different groups and entities that are involved in this space, and clarifying and coordinating their actions, will be critical to the success of policy efforts aimed at mitigating the risks of this market while promoting responsible progress in stem cell research.5 Numerous issues and concerns with the market for unproven stem cell-based interventions have been identified. Many for-profit clinics selling unproven stem cell-based interventions directly to patients take advantage of the hyperbole surrounding stem cell research6,7,8 to advertise their products and services. In many cases, interventions are sold that have no established biomedical or scientific basis (eg stem cell-based treatments for autism). In other instances, the interventions offered may be rooted in basic scientific findings and preliminary clinical experience, but currently have insufficient formal clinical testing to justify widespread clinical use (eg adipose derived stem cells for treatment of orthopedic injuries). At times, it appears that uncontrolled and non-standardized products are being administered, without credible evidence that the products contain active stem cells or have demonstrated any regenerative effects. In addition to other concerns (eg potential fraud and financial loss), when these unproven interventions are advertised and administered without an adequate evidence base, they risk causing serious injury to patients and violating professional and legal standards.9,10,11 For example, recent reports of adverse results include lesions of the spinal cord12 and retinal detachments following intraocular injection of adipose-derived stem cells.13 A comprehensive analysis of reported adverse events from patients who received unproven stem cell-based interventions published in 2018 details 35 cases of acute or chronic complications or death, emphasizing the potentially serious consequences of these unproven interventions.14 Early research investigating this global online direct-to-consumer marketplace for purported stem cell interventions revealed a preponderance of clinics in China, India, and Mexico.15,16 More recent research documents a growth of the market in such countries as the United States, Canada, Australia, and Japan.17,18,19,20 For example, one empirical study of the US direct-to-consumer marketplace for unproven stem cell interventions found over 350 businesses marketing putative ‘stem cell treatments’ for a wide range of diseases and injuries, and a recent update describes 716 clinics operating in 45 of the 50 US states.21 The risks associated with different supposed stem cell-based interventions available on the private market vary tremendously and depend on numerous factors including the source and type of cells used; the quality of harvesting and processing procedures and facilities; levels of procedural reproducibility and quality control; the manner and site of cell administration; the training and expertise of the health care team and the degree and quality of post-procedure care and follow-up. Leading scientific bodies such as the International Society for Stem Cell Research (ISSCR) have made important strides in developing voluntary guidelines for stem cell research and clinical translation pathways.22 However, as the global market for stem cell interventions continues to expand and diversify, it is increasingly difficult to draw sharp lines between what may constitute responsible and ethical instances of medical innovation,23,24 and activities that are clearly unethical because of the inappropriate personal financial burden they may create for the patient, the risks they pose, the uncertainties about their risks, or the lack of any potential benefits. This murkiness and the growing difficulties associated with identifying clear ‘red flags’ of problematic commercial activity creates challenges for prospective patients, health care providers, and regulators alike. We suggest that there is a need for policy makers and stakeholders to focus on achieving informational clarity about stem cell interventions in three key and interconnected areas, each of which carries different responsibilities for those involved: (i) with regulation that is clear and comprehensive, as well as consistently and robustly enforced; (ii) with scientific and clinical transparency, and (iii) with patient communication and engagement strategies that prioritize informed decision-making, accurate representations, and realistic expectations. Improvements in each of these domains depends on progress in the others. Effective regulation requires scientific and clinical precision. Similarly, truly informed decision-making by patients demands a clear understanding of scientific and clinical realities, while responsible scientific and clinical progress is facilitated by clear and consistent regulation that oversees the production of a high-quality product, thus improving reliability, patient confidence, and decision-making. We situate our analysis and recommendations largely in the Canadian and US contexts. In both countries, we see opportunity for timely, strategic interventions to restrict proliferation of the most egregious and concerning forms of this market. We also note however that the global nature of this market demands an important role for international cooperation and coordination.