key: cord-0889419-urgbhwoi
authors: Turner, Leigh
title: Preying on Public Fears and Anxieties in a Pandemic: Businesses Selling Unproven and Unlicensed “Stem Cell Treatments” for COVID-19
date: 2020-05-07
journal: Cell stem cell
DOI: 10.1016/j.stem.2020.05.003
sha: ef1da2abdc6caf0a853768a5eba9d8ae9a1bbaef
doc_id: 889419
cord_uid: urgbhwoi

Abstract 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 cells-based products, and undermine efforts to develop evidence-based treatments for COVID-19.

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), has in a matter of months become a devastating global pandemic and public health emergency (Centers for Disease Control and Prevention, 2020; World Health Organization, 2020) . The relative ease of transmission of the virus, the death, illness, and suffering it has caused, its ability to overwhelm health care systems, and its disruption of social life and economic structures make the disease a source of panic, anxiety, and fear. Tapping into overwhelming public interest in the development of effective vaccines and therapies for COVID-19, some businesses are promoting stem cells-based interventions or exosome products that supposedly treat or prevent COVID-19 or the acute respiratory distress syndrome (ARDS) experienced by some victims of the virus (Knoepfler, 2020) . The purported stem cell treatments these companies sell are unproven, have not been approved by the U.S. Food and Drug Administration (FDA) or other national regulatory bodies, pose risks to patients, and have the potential to undercut efforts to develop evidence-based stem cell treatments and other therapeutic products.

For more than a decade, businesses selling unproven and unlicensed stem cell interventions have claimed to treat individuals with illnesses or injuries for which effective therapies or cures are in fact unavailable. Patients with Alzheimer's disease, chronic obstructive pulmonary disease, amyotrophic lateral sclerosis, spinal cord injuries, and many other diseases and injuries have all been the focus of clinics that use aggressive marketing tactics to exploit hope, desperation, and vulnerability (Turner and Knoepfler, 2016) . Several businesses selling unlicensed stem cell products have been sued by patients alleging they were defrauded, injured, victims of elder abuse, or otherwise harmed (Horner, Tenenbaum, Sipp, and Master, 2018) .

Lacking convincing evidence to support their advertising claims, clinics instead solicit clients by using such tokens of legitimacy as scientific-seeming rhetoric and references to published pre-clinical and clinical studies (Sipp et al., 2017) . Clinics selling purported stem cell treatments or "immune-boosting" preventive therapies for COVID-19 and Covid-19 related ARDS exhibit this familiar pattern of using inaccurate advertising claims to make what they are promoting seem credible and worth purchasing.

Perhaps seeking to avoid attracting the scrutiny of regulatory bodies such as the FDA and Federal Trade Commission (FTC), some of these businesses make vague claims on their websites about stem cell treatments for COVID-19. A few businesses have posted to their websites videos of physicians expressing enthusiasm for the supposed promise of stem cell interventions for COVID-19. The sites encourage prospective customers to complete an online form or call and arrange a consultation if they want to learn more about what the clinics are selling. Other companies are less circumspect. Their advertising claims provide insight into how clinics promoting unproven and unlicensed stem cell products are using the pandemic as an opportunity to profit from fearful patients.

For example, a Colorado-based business is advertising "Mesenchymal Stem Cell Exosomes" as a "Viral Inhibitor and Immune System Booster" (see Supplementary materials for a summary list of online sources). The clinic's website states that the "Stem Cell Center now has a single visit Stem Cell Exosome IV treatment for patients that need to boost their immune system and have a powerful viral inhibitor. This treatment is for those who do not have Covid-19 but for those who want additional defense against the virus." The company claims that individuals with autoimmune disease, COPD, lung disease, ARDS, or who are more than sixty years old and have underlying health conditions "may benefit" from the procedure. "Our goal," the business claims, "is to give our patients peace of mind knowing that they've done everything possible to protect themselves and their family." Individual patients are charged $3,000 for the procedure, two family members are charged "$2,700 per person," and three or more family members are charged "$2,200 per person."

A company with clinics located in Pennsylvania and Delaware issued a press release claiming the business is "Now Offering Mesenchymal Stem Cell Treatments to Support Lung Health During COVID-19" (https://www.einnews.com/pr_news/512455640/pa-greenwellness-is-now-offering-mesenchymal-stem-cell-treatments-to-support-lung-healthduring-covid-19). "In the wake of a global health crisis," the company claims, it "has adapted its signature wellness injection to aid in lung health, restoration of damage and an overall reduction in inflammatory responses." Referencing a small clinical study conducted in China in which mesenchymal stem cells were administered to subjects diagnosed with COVID-19, the CEO of the company is quoted in the press release as stating, "This goes to support the wide range of healing and restoration that can be provided by MSC therapy.

While this isn't a cure or a vaccine against this new coronavirus, this technology may have the ability to reverse lung damage in patients and improve their overall health, which puts them in a much better position if they should find themselves with a COVID-19 infection."

In Arizona, a "regenerative medicine clinic" is advertising "stem cell therapy" as a "precautionary measure" for preventing Covid-19. The company's website states, "the anti inflammatory and healing properties of stem cells can help patients form a formidable barrier against the virus. This is especially true for patients who are less equipped to fight off infections due to a weaker immune system, other illnesses or aging." The clinic's website adds, "fortifying the lungs with umbilical cord tissue that contains millions of potent stem cells is a great way for patients to boost their ability to fight off virus and other related illnesses."

A Florida-based business selling purported stem cell treatments for COVID-19 offers conflicting messages, cautioning it is not claiming its stem cell products can treat or cure COVID-19 or any other infection or disease, while also stating in a section of its website entitled "Stem Cell Therapy And COVID-19," "Lung function and inflammation have been the main concern with the coronavirus. The damage to lung tissues can be fatal, and stem cell therapy has been shown to help repair the damage. According to our protocols, we can inject stem cells directly into the area of concern. Researchers have typically been injecting the stem cells directly into the lungs. Stem cells injected directly into the lungs have been shown to improve the immunity in the lungs and reduce the risk of pulmonary failure caused by inflammation." The company's website notes, "It's possible that your body needs an extra boost to help your immunity. To help our patients stay as healthy as possible, we are offering an array of immune boosting IV infusions. We also offer our existing stem cell therapy packages including IV exosomes." The business encourages potential clients with questions to call "and schedule a free phone conversation with one of our Regenerative Medicine Doctors."

Finally, a California-based "anti-aging clinic" is using YouTube videos to promote "stem cell exosome" products that it ships to the homes of clients. Rather than traveling to the clinic, clients instead receive "mesenchymal stem cell exosomes" delivered on dry ice, a vaporizer, mask, and additional equipment that they are then supposed to use to self-administer the nebulized product at home. The clinic's spokespersons claim the "stem cell exosome vapor treatments" promote lung tissue regeneration, strengthen the lungs and immune system, reduce inflammation, and "interrupts virus multiplication."

Not all U.S. companies advertising purported stem cell-based interventions for COVID-19 or COVID-19-related ARDS administer these products to patients at U.S.-based clinics. A business in Colorado that processes and distributes umbilical cord-derived stem cells is transporting its allogeneic stem cell product to a facility in the Caribbean. The company states, "We presently supply our Mesenchymal Stem Cells to" a clinic "in the Cayman Islands for treatment of inflammatory conditions. We are pleased to be positioned to offer stem cell therapy for Coronavirus infection. While there are several factors related to the possible extent of this global infection, stem cell therapy represents a therapeutic option to fight the virus and increase survival, while effective vaccines are being developed." At least one other U.S.-based company engaged in processing and distributing umbilical cord tissue-derived "mesenchymal stem cell products" is also preparing for marketplace entry by promoting itself as a supplier of allogeneic cell-based therapies that might be helpful in treating individuals diagnosed with COVID-19.

Other businesses are promoting biobanking of stem cells as a potential therapeutic insurance policy for COVID-19. These companies encourage healthy prospective clients to store their autologous stem cells for possible future therapeutic use in the event of subsequent diagnosis with COVID-19 or COVID-related ARDS. Some businesses advertise both stem cell interventions for COVID-19 and banking of stem cells for future use. For example, the Facebook page of a clinic in Alabama states, "We have the option of providing patients with immediate (point of care) production of SVF (stem cells produced from your own fat used the same day) and/or the option of having mini liposuction and then banking your own adipose stem cells for expansion into very high numbers (similar to China).

These stored 'personal stem cells' will allow you to have cells available urgently should you contract a potentially lethal virus and become eligible for 'right to try' access to your cells.

Having a frozen line of one's own personal mesenchymal stem cells could prove life-saving should someone become a victim of the current viral pandemic."

Many of the businesses advertising supposed stem cell therapies or exosome treatments for COVID-19 are using press releases and their websites to connect their products to news media reports and press alerts that enthusiastically describe "cures" and breakthroughs" in China following the administration of stem cells to individuals who were diagnosed with COVID-19. The title of one such article states, "Chinese Doctor Claims He Has Found 100% Cure For Coronavirus" (https://www.albawaba.com/editors-choice/chinese-doctorclaims-he-has-found-100-cure-coronavirus-1345690). Another article is entitled, "Chinese doctor claims he made a breakthrough in coronavirus pandemic with stem cell injectionshaving 100% success rate after treating nine mostly elderly patients" (https://www.dailymail.co.uk/news/article-8116881/Doctor-claims-breakthrough-stemcell-injections-treat-coronavirus.html). A third article is titled, "Coronavirus: critically ill Chinese patient saved by stem cell therapy, study says"

(https://www.scmp.com/news/china/society/article/3053080/coronavirus-critically-illchinese-patient-saved-stem-cell). These uncritical news media reports are used as "evidence" that the "mesenchymal stem cell treatments" or "exosome therapies" these clinics are selling will benefit their clients.

Hyping of pre-clinical and clinical findings is a longstanding problem in the field of stem cell research (Caulfield, Sipp, Murry, Daley, and Kimmelman, 2016 covid-19-and-stem-cells) have all expressed concern about clinics selling unproven stem cell interventions for COVID-19. These bodies rightly that note there are no approved and evidence-based stem cell therapies for COVID-19 and businesses should not sell unproven and unapproved products as treatments. Statements from these organizations matter.

However, in terms of their ability to directly regulate conduct, these scientific communities typically are confined to expelling members that do not meet their standards for responsible conduct. They have no broader regulatory authority to investigate businesses selling unapproved stem cell interventions. Their warnings are important but ultimately law enforcement agencies and regulatory bodies are responsible for taking action against noncompliant businesses and clinicians.

Despite commendable efforts by various scientific societies to criticize deceptive advertising of stem cell products for treatment or prevention of COVID-19, at least two organizations are engaging in activities that risk propagating the misrepresentation that there are evidence-based stem cell therapies now available for COVID-19.

For example, the American Academy of Stem Cell Physicians, an organization with many members drawn from participants in the direct-to-consumer stem cell "industry," recently submitted to World Health Organization Director Dr. Tedros Adhanom Ghebreyesus a letter containing a recommended treatment protocol for individuals diagnosed with COVID-19 (https://www.prnewswire.com/news-releases/the-american-academy-of-stemcell-physicians-recommends-a-treatment-protocol-for-covid-19-to-the-who-301026685.html). The Academy's list of recommendations includes administering to hospitalized patients diagnosed with COVID-19 umbilical cord blood and "nebulizer with Amniotic fluid derived Exosomes." The letter provides no scientific evidence supporting the use of these products in the care of individuals with COVID-19.

Another organization, the American Society for Interventional Pain Physicians, issued a statement in which the Society claims it is "asking authorities to approve expanded umbilical cord stem cell infusions for treatment"

(https://files.constantcontact.com/a496a007601/1e9e53f1-c9af-4f53-913d-871dd86edc4c.pdf). In an accompanying article, members of the Society call for compassionate access to such products in the care of patients with COVID-19 (Atluri,

Manchikanti, Hirsch 2020).

The two associations claiming birth tissue-derived stem cell products are safe and effective treatments for COVID-19 lack the public standing and reach of societies such as ISSCR and

ISCT. Nonetheless, their public messaging risks spreading the misrepresentation that a substantial body of evidence already supports the safe and efficacious use of stem cell products in the care of individuals with COVID-19.

There are legitimate scientific reasons to pursue clinical research testing the safety and efficacy of various stem cell products in the care of individuals with COVID-19 (Khoury, M. Cuenca, J., Cruz, F., Figueroa, F., Rocco, P., Weiss, D. 2020 already begun reviewing such studies and clearing them to commence recruiting study participants. To provide proper oversight of submitted clinical studies and the investigational products they are designed to test, the FDA will need to be able to exercise its regulatory authority free from political pressure and other attempts to influence its review and approval processes (Thomas, K. 2020) .

Some studies testing stem cell products for COVID-19 lack blinding, randomization, and a control arm, have small sample sizes, are conducted at a single clinical site, suffer from additional limitations, and are unlikely to generate high-quality safety and efficacy data. An additional concern with such poorly designed or very preliminary studies is that despite not having the capacity to generate robust evidence they could lead to patients with COVID-19 seeking access to unproven stem cell products on a Right-to-Try basis. In contrast, other studies are well-designed, multi-center randomized controlled trials that should generate valuable data concerning whether particular stem cell-based products can be used to treat individuals with COVID-19. Funding agencies are also providing support for stem cell research related to COVID-19. For example, the California Institute for Regenerative

Medicine approved $5 million in emergency funding that will be used to support research intended to develop therapies for COVID-19 (https://www.cirm.ca.gov/aboutcirm/newsroom/press-releases/03272020/stem-cell-agency-board-approves-5-millionemergency).

The Acknowledging the serious challenges currently facing the FDA and FTC, state oversight bodies, and their counterparts in other countries, regulatory bodies and law enforcement authorities tasked with addressing pandemic-related fraud and other forms of noncompliant activity should be alert to additional businesses peddling purported stem cell therapies and exosome treatments for COVID-19 and COVID-related ARDS. Such companies make misleading claims, expose patients to potentially risky products, promote false hope and might lead some individuals to place less emphasis on physical distancing and sheltering in place measures, and administer unproven stem cell interventions that likely will result in the subsequent exclusion of recipients from well-designed and competently conducted clinical studies.

Regulatory bodies such as the FDA and FTC must make challenging resource allocation decisions when deciding whether to investigate particular businesses. The commercial and clinical activities of businesses selling purported stem cell treatments and preventive measures for COVID-19 constitute sufficient risks to patient safety, public health, and truthfulness in advertising and commerce to warrant further investigations and enforcement actions. Patients need evidence-based therapies, preventive measures, and supportive care for COVID-19 rather than unproven and unapproved products marketed as effective treatments.

Coronavirus (COVID-19)

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Unproven Stem Cell Therapy Gets OK for Testing in Coronavirus Patients. The New York Times

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Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics

Current Status of Cellbased Therapies for Respiratory Virus Infections: Applicability to COVID-19

Cell-Based Therapies for COVID-19: Proper Clinical Investigations are Essential. Cytotherapy. Pre-proof published online

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