Effective regulatory responses to predatory stem cell markets in Australia and Canada.

The rapid proliferation of businesses engaged in direct-to-consumer advertising of unproven stem cell interventions has raised troubling questions about whether government bodies can regulate this health market effectively. Recent developments in Australia and Canada suggest that such fears are unfounded and that targeted regulatory action can have meaningful effects.

US businesses engaged in direct-to-consumer marketing of perinatal stem cell interventions following the Food and Drug Administration's enforcement discretion era.

BACKGROUND AIMS: The goal of this study was to analyze online marketing representations made by 300 US businesses selling allogeneic perinatal stem cell products. The study was conducted after a period of enforcement discretion by the US Food and Drug Administration (FDA). METHODS: Data mining and content analysis were used to identify, analyze and categorize marketing claims made on the websites of 300 businesses selling perinatal stem cell interventions. RESULTS: The study identified types of perinatal interventions companies advertised, geographic locations of clinics selling such products, types of companies operating in this space, diseases and injuries such businesses claim to treat, prices companies charge for such interventions, brand names of advertised perinatal cell products and identities of suppliers. CONCLUSIONS: A substantial number of US businesses market unapproved perinatal stem cell products for various indications. This widespread commercial activity occurred following the conclusion of a period of enforcement discretion by the FDA and suggests the need for more robust and comprehensive regulatory responses to businesses selling unapproved perinatal stem cell products.

Businesses marketing purported stem cell treatments and exosome therapies for COVID-19: An analysis of direct-to-consumer online advertising claims.

We identified 38 businesses advertising purported stem cell interventions and exosome products for COVID-19. These companies operated or facilitated access to 60 clinics. More than 75% of these clinics were based in the United States and Mexico. Thirty-six of the businesses marketed their stem cell and exosome products as treatments for Long COVID, six advertised them as "immune boosters," five claimed to treat patients in the acute infection phase, and two claimed their products were preventive. The least expensive product cost $2,950, the most expensive was $25,000, and the average listed cost for patients was $11,322. The promotion of these products is concerning because they have not been approved by national regulators and do not appear to be supported by convincing safety and efficacy data.

Regulatory claims made by US businesses engaged in direct-to-consumer marketing of purported stem cell treatments and exosome therapies.

Aim: This study investigated whether US businesses engaged in direct-to-consumer online marketing of purported stem cell therapies and stem cell-derived exosome products made claims concerning the regulatory status of these interventions. Methods: We used data mining and content analysis of company websites to examine regulatory-related representations made by US businesses marketing stem cell treatments and exosome therapies. Results: More than two thirds of such businesses did not make explicit representations about the regulatory status of their marketed products. Businesses that made claims about the regulatory status of the stem cell and exosome products they sold used range of representations concerning the legal standing of these interventions. Conclusion: The absence of information addressing the regulatory status of stem cell interventions and exosome products and the use of what appeared to be inaccurate information concerning the regulatory status of numerous products likely complicates efforts by customers to make informed health-related decisions.

Safety and efficacy claims made by US businesses marketing purported stem cell treatments and exosome therapies.

Aim: Examining websites of US businesses engaged in direct-to-consumer advertising of putative stem cell treatments and exosome therapies, this study investigated the marketing claims such companies make about the purported safety and efficacy of these products. Methods: Data mining and content analysis of company websites were used to identify and analyze safety and efficacy claims. Results: Of the 978 businesses analyzed, less than half the companies made identifiable claims about the safety and efficacy of their advertised stem cell and exosome products. We also explored how companies framed the stem cell and exosome products they promoted. Representations ranged from assertions that such products are unproven and investigational to claims they constituted cures. Most advertising frames fell between these poles. Conclusion: Some businesses include in their marketing representations claims about the safety and efficacy of advertised products. Businesses that did not make such assertions use other techniques to attract prospective clients.

International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products.

The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles. Since its inception, the International Society for Cell & Gene Therapy Committee on the Ethics of Cell and Gene Therapy has opposed the premature commercialization of unproven cell- and gene-based interventions and supported the development of evidence-based advanced therapy products. In the present Guide, targeted at International Society for Cell & Gene Therapy members, we analyze this industry, focusing in particular on distinctive features of unproven cell and cell-based products and the use of tokens of scientific legitimacy as persuasive marketing devices. We also provide an overview of reporting mechanisms for patients who believe they have been harmed by administration of unapproved and unproven products and suggest practical strategies to address the direct-to-consumer marketing of such products. Development of this Guide epitomizes our continued support for the ethical and rigorous development of cell and cell-based products with patient safety and therapeutic benefit as guiding principles.

An International Society for Cell & Gene Therapy working group short report on the future of expanded access to unapproved cell and gene therapies.

Patient interest in non-trial access pathways to investigational cell-and gene-based interventions, such as expanded access in the USA, is increasing, while the regulatory and business environments for non-trial access in the cell and gene therapy field are shifting. Against this background, in 2022 the International Society for Cell & Gene Therapy (ISCT) established a Working Group on Expanded Access to identify practical, ethical, and regulatory issues emerging from the use (and possible misuse) of the expanded access pathway in the cell and gene therapy field. In this Short Report, the Working Group sets the stage for its future activities by analyzing the history of expanded access and identifying three examples of questions that we anticipate arising as uses of expanded access for investigational cell and gene-based interventions increase and evolve.

Stem cells, cell therapies, and bioengineering in lung biology and disease 2021.

The 9th biennial conference titled "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases" was hosted virtually, due to the ongoing COVID-19 pandemic, in collaboration with the University of Vermont Larner College of Medicine, the National Heart, Lung, and Blood Institute, the Alpha-1 Foundation, the Cystic Fibrosis Foundation, and the International Society for Cell & Gene Therapy. The event was held from July 12th through 15th, 2021 with a pre-conference workshop held on July 9th. As in previous years, the objectives remained to review and discuss the status of active research areas involving stem cells (SCs), cellular therapeutics, and bioengineering as they relate to the human lung. Topics included 1) technological advancements in the in situ analysis of lung tissues, 2) new insights into stem cell signaling and plasticity in lung remodeling and regeneration, 3) the impact of extracellular matrix in stem cell regulation and airway engineering in lung regeneration, 4) differentiating and delivering stem cell therapeutics to the lung, 5) regeneration in response to viral infection, and 6) ethical development of cell-based treatments for lung diseases. This selection of topics represents some of the most dynamic and current research areas in lung biology. The virtual workshop included active discussion on state-of-the-art methods relating to the core features of the 2021 conference, including in situ proteomics, lung-on-chip, induced pluripotent stem cell (iPSC)-airway differentiation, and light sheet microscopy. The conference concluded with an open discussion to suggest funding priorities and recommendations for future research directions in basic and translational lung biology.

Adverse events related to unapproved stem cell products and other regenerative interventions: recommendations for more robust regulation of the direct-to-consumer marketplace.

Tweetable abstract Adverse events continue to occur in the direct-to-consumer market for unapproved regenerative interventions and the US FDA alone cannot adequately address the problem. Other public health strategies are needed to provide better patient protection.

The American stem cell sell in 2021: U.S. businesses selling unlicensed and unproven stem cell interventions.

In March 2021, 1,480 U.S. businesses operating 2,754 clinics were found selling purported stem cell treatments for various indications. More than four times as many businesses than were identified 5 years ago are selling stem cell products that are not FDA-approved and lack convincing evidence of safety and efficacy.

Ethical issues and public communication in the development of cell-based treatments for COVID-19: Lessons from the pandemic.

The significant morbidity and mortality of coronavirus disease 19 (COVID-19) prompted a global race to develop new therapies. These include interventions using cell- or cell-derived products, several of which are being tested in well-designed, properly controlled clinical trials. Yet, the search for cell-based COVID-19 treatments has also been fraught with hyperbolic claims; flouting of crucial regulatory, scientific, and ethical norms; and distorted communication of research findings. In this paper, we critically examine ethical issues and public communication challenges related to the development of cell-based therapeutics for COVID-19. Drawing on the lessons learned from this ongoing process, we argue against the rushed development of cell-based interventions. We conclude by outlining ways to improve the ethical conduct of cell-based clinical investigations and public communication of therapeutic claims.

ISSCR's Guidelines for Stem Cell Research and Clinical Translation: Supporting development of safe and efficacious stem cell-based interventions.

The ISSCR's revised Guidelines for Stem Cell Research and Clinical Translation reflect the organization's commitment to opposing premature commercialization of stem cell-based interventions and supporting the development of products that meet stringent ethical, scientific, and regulatory standards. The Guidelines contain five important new recommendations concerning clinical translation of stem cell products.

ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update.

The International Society for Stem Cell Research has updated its Guidelines for Stem Cell Research and Clinical Translation in order to address advances in stem cell science and other relevant fields, together with the associated ethical, social, and policy issues that have arisen since the last update in 2016. While growing to encompass the evolving science, clinical applications of stem cells, and the increasingly complex implications of stem cell research for society, the basic principles underlying the Guidelines remain unchanged, and they will continue to serve as the standard for the field and as a resource for scientists, regulators, funders, physicians, and members of the public, including patients. A summary of the key updates and issues is presented here.

Ethical issues concerning a pay-to-participate stem cell study.

In our critique of a pay-to-participate study, we address how the failure to disclose study-related payments appears to have violated STEM CELLS Translational Medicine's editorial policies concerning conflict-of-interest and financial disclosure. Our analysis also identifies broader ethical issues and scientific concerns related to pay-to-participate studies conducted by businesses with a record of selling purported stem cell treatments before determining whether the products they sell are safe and efficacious. Authors of peer-reviewed articles have a responsibility to comply with journal policies and disclose financial conflicts of interest to editors, reviewers, and readers. Authors should also disclose when stem cell interventions being tested in clinical trials have already been sold on a direct-to-consumer basis as "stem cell treatments" by authors' affiliate institutions. Financial conflicts of interest and other forms of possible bias must be disclosed to put clinical studies in context and facilitate the critical assessment of research methods, findings, and conclusions. The apparent failure to comply with journal editorial policies and disclose such financial conflicts warrants careful investigation.

Crowdfunding, stem cell interventions and autism spectrum disorder: comparing campaigns related to an international "stem cell clinic" and US academic medical center.

BACKGROUND AIMS: Studies examining crowdfunding campaigns for stem cell interventions have typically focused on campaigns seeking funds to send individuals to businesses marketing unlicensed and unproven stem cell products. However, some crowdfunding campaigns identify academic medical centers as destinations for individuals seeking access to stem cell products provided either in clinical studies or on an expanded access basis. This study examines crowdfunding campaigns seeking funds to enable children diagnosed with autism spectrum disorder access to stem cell interventions. METHODS: This study compares and contrasts crowdfunding campaigns, identifying an international stem cell clinic marketing a purported umbilical cord blood-derived stem cell treatment for autism spectrum disorder, with campaigns soliciting donations intended to help children with autism spectrum disorder either participate in clinical studies or obtain expanded access to stem cell products provided at an academic medical center in the US. RESULTS: Campaigns connected to both sites contained inaccurate claims. However, campaigns identifying the international clinic as the intended destination site made stronger claims about efficacy and were more reliant upon testimonials than campaigns listing the US-based academic medical center as the planned clinical site. Acknowledging these important distinctions, clinical studies and press releases associated with the academic medical center played an important role in lending the perception of credibility to the putative stem cell treatments marketed by the international clinic. CONCLUSIONS: The study's findings emphasize how important it is for researchers at academic medical centers and comparable research facilities to avoid engaging in stem cell hyperbole; highlight the preliminary nature of early clinical studies; ensure that any claims about safety and efficacy are based upon robust and reliable evidence; and promote responsible science communication by exercising restraint when crafting press releases, conducting media interviews and otherwise publicizing clinical research findings.

Is right to try being tried? Using crowdfunding data to better understand usage of nontrial pre-approval access pathways.

Aim: The US FDA has two nontrial pre-approval access pathways: expanded access (EA) and right to try (RTT). Reports of successful RTT use are scarce, and the FDA has not yet published RTT usage data, yet proponents tout its utility. In the face of this discrepancy and a lack of transparency of usage statistics, our aim is to add to the limited understanding of RTT usage. Materials & m ethods: We searched crowdfunding campaigns referencing 'expanded access', 'right to try' or 'compassionate use' since 2018. Results: We identified 26 EA campaigns, 29 RTT campaigns and two referencing both. Twenty one EA campaigns described being approved to receive access to the requested experimental medical product versus one RTT campaign. Conclusion: RTT is associated with poor understanding of nontrial pre-approval access. These campaigns suggest RTT is not offering a practical alternative to EA. Cost remains a significant barrier to these patients.

Preying on Public Fears and Anxieties in a Pandemic: Businesses Selling Unproven and Unlicensed "Stem Cell Treatments" for COVID-19.

In the midst of a global public health emergency, some businesses are taking advantage of widespread fears by marketing purported stem cell treatments for COVID-19. Such businesses target prospective clients with misleading claims, expose patients to potentially risky stem cell-based products, and undermine efforts to develop evidence-based treatments for COVID-19.

Challenging misinformation and engaging patients: characterizing a regenerative medicine consult service.

Aim: To address the unmet needs of patients interested in regenerative medicine, Mayo Clinic created a Regenerative Medicine Consult Service (RMCS). We describe the service and patient satisfaction. Materials & methods: We analyzed RMCS databases through retrospective chart analysis and performed qualitative interviews with patients. Results: The average patient was older to elderly and seeking information about regenerative options for their condition. Patients reported various conditions with osteoarthritis being most common. Over a third of consults included discussions about unproven interventions. About a third of patients received a clinical or research referral. Patients reported the RMCS as useful and the consultant as knowledgeable. Conclusion: An institutional RMCS can meet patients' informational needs and support the responsible translation of regenerative medicine.