Online seminars as an information source for direct-to-consumer stem cell therapy

Abstract

Aim:

To attend stem cell (SC) seminars hosted by US-based direct-to-consumer SC businesses either in person or via online ‘webinars’ to determine accuracy and regulatory oversight of the advertised SC therapies.

Methods:

The therapeutic claims, costs, risks, scientific evidence in support of a therapy and any regulatory oversight were collated using pre-established checklists. Participation consisted of one live attendance of a seminar, and following COVID-19 restrictions, review of seven recorded presentations available on the internet from SC businesses.

Results & conclusion:

None of the SC therapies advertised by direct-to-consumer clinics reviewed were supported by proper clinical evidence nor substantiated by peer reviewed literature.

Background

Stem cells (SCs) hold promise to treat a variety of diseases because of their regenerative potential to replace or repair many organs or tissues. SCs are unique in that they can either self-renew or differentiate to form more than one terminal cell type found in the human body. Although innovative SC therapies are at the forefront of research, it is important for such treatments to be first carefully assessed through rigorous scientific investigation and to be approved by regulatory agencies to ensure safety and efficacy before translation into clinical practice.

For a medical product to be licensed in the USA and marketed as an approved therapy, it must first demonstrate safety and efficacy in a series of controlled clinical trials as part of a Biologics License Application (42 US Code § 262) [1]. The US FDA evaluates the safety and efficacy of new biologics or Biologics License Applications by reviewing their preclinical and clinical trial results before approval for commercialization is granted, making the therapy ‘approved’ or a ‘licensed’ biologic. In fact, we have argued that the FDA should add a requirement that the intended biologic product be validated in preclinical (animal) testing before testing in humans is allowed [2,3]; currently, this is not a requirement.

Currently, there are 22 licensed ‘biologics’ or products on the FDA’s ‘Approved Cellular and Gene Therapy Products’ website [4] (visited 21 September 2021). However, five are genetically modified T-cell products, three are gene therapies and one is a human protein. Of the remaining 11, seven are blood derived progenitors, three are skin progenitors and one is derived from cartilage progenitors (chondrocytes). None are bonafide SC-derived products generated from induced pluripotent SCs, fetal SCs or embryonic stem cells, although biologics derived from such sources have been or currently are being tested in FDA-regulated clinical trials.

It is important to note that FDA-regulated clinical trials are not the same as approved or licensed therapies. A FDA-regulated clinical trial indicates a therapy is to be tested in patients who fit the inclusion criteria set out in a trial protocol. The data from the trials of the new therapy are reviewed by the FDA and the therapy then either becomes an approved, licensed therapy or not, as determined by the FDA. An SC provider wishing to administer experimental SC therapies as part of a clinical trial must apply for an investigational new drug (IND) application with the FDA, who then grants (or does not) the IND for a clinical trial. This process includes FDA review of preclinical data, the study plan/protocol and patient informed consent document(s) and requires additional approval of relevant patient materials by a certified institutional review board (IRB). IRBs are concerned with the welfare of patients. Before a clinical trial may begin, the IRB reviews and approves (or not) the study and patient materials [5]. The direct-to-consumer (DTC) SC businesses discussed in this article are all in the USA and may be attempting to circumvent these regulations by delivering non-FDA-approved SC treatments or circumventing ‘minimally manipulated’ guidelines [6]. The criteria in 21 CFR 1271.10(a)(1) and 21 CFR 1271.10(a)(2) for ‘minimal manipulation’ and ‘homologous use’ by the FDA may be circumvented by many SC clinics and is often used as a technique to avoid regulatory oversight [7–9].

As a response to patient demands for innovative SC therapies, commercialization of unapproved SC therapies by private, for-profit clinics, has quickly proliferated. Unapproved SC therapies offered by these clinics may lack scientific evidence of safety and efficacy (and therefore, have not been approved or obtained premarketing authorization by the FDA). Such providers may be exposing patients to serious physical harm and financial distress, falling short of their medical responsibility to the public (for reviews, see [10,11]). This raises legitimate ethical concerns. One example is a La Jolla clinic that had operated under the name of ‘StemGenex’ and disclosed its revenue from 2017 to be an estimated US$8.2 million, as the clinic was recommending more than one treatment for their patients and charging per treatment [12]. StemGenex is an example of a clinic that was ‘registered’ or listed on ClinicalTrials.gov website, a website that does not review the validity of the registration claims [13,14]. The FDA warned StemGenex that it was illegally marketing an unregulated SC product [15]. The clinic filed for bankruptcy following a class-action lawsuit brought by former patients for the clinic’s misleading advertisement and marketing claims. Another such example is a Florida clinic that registered its unauthorized clinical trial on ClinicalTrials.gov to provide SC therapy for macular degeneration. Three patients became permanently blind following such treatment. This horrific episode is described in an article published in the Washington Post [16] as representing “one of the most egregious examples of patient injury involving a stem cell clinic” [17].

Methods

This study reports on primary data collection of SC therapy claims made by private, DTC SC businesses during their presentation talks to potential patients. Eight DTC SC businesses were randomly selected through a YouTube and Google search using the terms ‘stem cell treatments’, ‘stem cell interventions’, ‘stem cell therapies’, ‘stem cell seminars’, ‘stem cell webinars' and 'stem cell presentations’. Seven of the businesses were SC clinics and one business was not classified as a clinic but was included in our analysis as it directly sold to consumers products for which the business made SC claims. All businesses were located in the USA.

Participation for this analysis consisted of one live attendance of a seminar, independent audio and visual attendance of two recorded video webinars and four recorded seminars, and one video recording that was not titled as a ‘seminar’ or ‘webinar’ but was identified as a camera recorded talk by a clinic member to an audience and posted on the internet for further reach to potential patients [18]. Letters were assigned for all eight businesses in this analysis to anonymize their identities and to protect the authors from frivolous lawsuits. All recordings were posted online between the years of 2016 and 2020 and the live attendance took place in 2020.

A seminar checklist was developed as a data collection tool to support the gathering of essential information such as medical conditions treated, cost of advertised interventions, source and type of cells offered, number of treatments said to be typical, number of cells injected per intervention, route of administration, assurance of cell quality, mention of the FDA or any regulatory oversight, mention of supporting clinical evidence, reported adverse or side effects, reported clinical benefits and safety claims.

Additionally, the SC business websites were reviewed to note any further claims or information provided to patients. For example, some clinic websites contained a list of references to serve as evidence of safety and efficacy of the advertised SC therapies. The list of references was reviewed to assess credibility of source, phase of reported studies and whether there is a match between the cell source and therapeutic area with the business’s advertised cell source and therapeutic area(s) treated.

Some of the clinics mentioned in this study treat conditions using interventions other than SC treatments, which we did not list in this article. For purposes of this article, only conditions treated by the clinics’ interventions involving SCs or derivatives of SCs were reported.

Results

Checklists

A total of eight checklists were completed. Seven checklists were completed for seven clinics, and one checklist was completed for one business that was not classified as a clinic but sells directly to consumers products for which the business made SC claims. The eight businesses were spread across the USA: California, Florida, Illinois, Michigan, Nevada, New York, Ohio and South Carolina. Letters were assigned to each business as follows: ‘A’ for the business not classified as a clinic, ‘B’, ‘C’, ‘D’, ‘E’, ‘F’, ‘G’ and ‘H’ for the seven clinics.

Categories of checklist responses

We classified the responses within the SC checklist that was used to collect data into the following six categories.

Medical conditions treated

Business A claimed that their advertised skin patches work to cure infections in dogs, bears, horses and people. The presenter’s relative was walked to the front of the room as an example of someone who had benefited tremendously from the advertised patches. Although the relative did not speak to the audience himself, he stood while the presenter explained that he had been diagnosed with Alzheimer’s disease and prescribed many medications, but the patches had led to improved memory, being taken off all his medications and having the ability to walk again. The presenter explained to the audience that their marketed patches are said to improve, if not completely cure, Alzheimer’s disease, insomnia, anxiety, depression, stress as well as lead to hair growth. The patch was said to ‘activate and mobilize the body’s SCs’.

As for the seven clinics (businesses B–H), the presenters and their respective clinic websites mostly targeted their interventions toward orthopedic conditions. Although some businesses also made claims that their treatments can also be offered for anti-aging, preventative measures, general rejuvenation and wellness, autoimmune diseases, chronic fatigue, male hormone replacement, hair loss and other various conditions. See Table 1 for medical conditions treated by each business.

Table 1. . Medical conditions treated by business.

Business/ clinic	Regenerative therapy	Arthritis joint pain	Spine medicine	Autoimmune diseases	Chronic pain and injury	Anti-aging or Alzheimer’s	Preventative measures	Hair loss	Male hormone replacement
A	x					x	x	x
B	x	x			x	x
C	x	x	x		x		x
D	x	x			x
E	x	x		x	x	x	x
F	x	x	x		x
G	x	x			x			x	x
H	x	x	x	x	x

Treatment cost

Business A offered a bundle price of less than US$200 for 30 patches or approximately US$90 for individual patches, and various other similar numbers for different patch types. Three of the seven clinics made their intervention costs available. For the four of the seven clinics that did not disclose a price in their presentation, their clinic websites were reviewed for any mention of costs, but treatment costs were not identified.

For the three clinics that indicated the price upfront, their prices ranged from US$4000 to 12,000 for their marketed interventions. One business charged by the ‘body part’ and offered a ‘multiple body part discount’, in addition to a seminar discount to those who have attended the seminar. Although cost was said to be based on body part, the various possible disease indications for body parts were not distinguished in relation to cost. Another business charged by the joint and by source of cells, offering a US$200.00 off per joint if an attendee of the seminar stayed for a consultation and paid a US$500 deposit on the day of seminar attendance. A third business did not mention cost during the presentation and cost on their website was not identified, but the speaker stated that their interventions cost anywhere from US$4000 to 12,000 in response to a question from an audience member about cost.

Source & type of cells

Table 2 presents each business's source and type of cells as reported by the clinic. This category more directly applies to seven clinics (businesses B–H), as business A sells patches which are said to activate and mobilize the user’s own SCs; therefore, ‘cell source’ is not directly applicable to business A or the source should be considered ‘autologous’.

Table 2. . Source and type of cells by business/clinic.

Business	Cell source	Cell type
Business A	Autologous stem-cell activating skin patch	Unknown
Clinic B	Allogenic	Human umbilical cord
Clinic C	Autologous and allogeneic	Umbilical cord, bone marrow and adipose
Clinic D	Autologous	Bone marrow
Clinic E	Allogenic	Umbilical cord
Clinic F	Autologous	Bone marrow
Clinic G	Allogenic	Umbilical cord
Clinic H	Autologous and allogeneic	Umbilical cord, adipose

Businesses B, C, D, F, G and H advertised direct SC therapies, where the offered interventions involved some form of injection of SCs directly into the patient. Business E, on the other hand, advertised ‘exosome’ therapies that are derived from SCs. As quoted by business E’s clinic website: “Our therapy uses exosomes excreted from mesenchymal stem cells derived from the umbilical cord, not the actual stem cells, as research has shown greater beneficial outcomes from exosome over stem cells with minimal risk. Exosomes used in our clinic are obtained from human umbilical cord stem cells.”

All seven clinics reported using allogeneic, autologous, or a mixture of both as sources for their SCs. Some clinics, such as business C, reported processing cells in house and even combining their injection with platelet rich plasma. The presenter stated: “We concentrate them, and we activate them using platelet rich plasma therapy and then we re-inject them. It’s safe, it’s controlled, we have full control of the environment and to date I have never had a complication in doing this for 10 years because we regulate it and it’s all done in house.” The speaker or the clinic website did not mention how the harvesting of cells in house was regulated.

Business B claimed that the cells they inject into their patients (derived from the umbilical cord), are provided by an FDA-regulated lab. However, the treatment being offered was not said to be regulated or approved by FDA. The presenter stated: “The FDA does not approve nor disapprove natural treatments. They approve food, drugs, and medical procedures. The FDA does regulate how these cells are housed and processed.”

Number of treatments typical, number of cells injected & route of administration

Table 3 presents the number of typical treatments, number of cells injected and route of administration as specified by business A and clinics B–H or otherwise unspecified. Regarding Business A, their marketed patches are nontransdermal, worn in 12-h cycles (12 h on/12 h off), and are said to work ‘through high vibration frequencies’ as indicated by the presenter. The website stated: “The patch duplicates young stem cells and deploys existing stem cells through epigenetics which works with our internal organs.”

Table 3. . Treatments typical, number of cells injected and route of administration by business/clinic.

Business/clinic	Treatments typical (n)	Cells injected (n)	Route of administration
Business A	Multiple	Not applicable	Transdermal-like patch
Clinic B	1	1.1 million	Injection (method of injection was unspecified)
Clinic C	Unspecified	Up to 500 million	Intravenous injection for orthopedic conditions (route of administration for other conditions was unspecified)
Clinic D	2–3	Unspecified	Injection (method of injection was unspecified)
Clinic E	Unspecified	Unspecified	Intravenous injection for systemic illnesses; intra-articular injections for joint therapy
Clinic F	Unspecified	Unspecified	Injection (method of injection was unspecified)
Clinic G	Unspecified	10–30 million	Intravenous injection
Clinic H	1–2	10 million	Intravenous injection, inhalation

Assurance of cell quality, FDA regulation, safety claims, clinical benefits & adverse/side effects

Table 4 presents statements made by the presenters or identified on the business websites in relation to the marketed intervention’s assurance of cell quality claims, mention of FDA, safety claims, clinical benefits and adverse/side effects. None of the clinics reviewed in this article were offering SC therapies that were FDA approved nor being investigated under an IND application.

Table 4. . Assurance of cell quality, US FDA regulation, safety claims, clinical benefits and adverse/side effects.

Theme/example quotes	Businesses (n)
The business mentioned FDA regulation of the marketed intervention and/or assurance of cell quality either during presentation or on own website: – “While stem cell therapy is overseen and regulated by the FDA it is NOT completely FDA approved. It’s speculated that stem cell therapy will be FDA approved in time, but as of now it’s only regulated by the FDA. Stem cell therapy is 100% legal to practice in the United States as long as the stem cells are gathered from a legal source, and the clinic administering the therapy follows proper medical procedures.” – “FDA allows for minimal manipulation [12] to happen during the transplantation phase.” – “The FDA does not approve nor disapprove natural treatments. They approve food, drugs, and medical procedures. The FDA does regulate how these cells are housed and processed.”	5
The business mentioned adverse/side effects of the marketed intervention: – “Small percentage of patients experience flu-like symptoms that last no longer than 24–48 hours. I personally never had that happen in my clinic, but that the lab does say that.” – “There may be mild soreness in the joint for up to a week after the procedure. Heavy exertion should be avoided during this period.” – “Patients experience minimal discomfort during the procedure, it’s a small injection that they can actually get up and walk out of the appointment that same days. There’s no sedation and no down time and the symptoms can begin to improve within 1 to 2 months of the treatment.”	7
The business mentioned clinical benefits obtained by the marketed intervention: – “The patch duplicates young stem cells and deploys existing stem cells through epigenetics which works with our internal organs.” – “15% see results within 24 hours. 60% see results by 8 weeks. Most of the tissue growth occurs from 3 to 8 months. Improvements can take up to one year.” – “Patients typically have 30% to 50% improvement from baseline.”	8
The business made safety claims for the marketed intervention: – “Stem cell therapy does not alter the DNA of other cells. Only carcinogens and viruses are able to negatively alter the DNA.” – “Stem cells hold the promise of treatment and cures far more than 70 major diseases that affect millions of people.” – “There’s no safety concerns or adverse effects that we've seen … I’ve never seen a rejection. I’ve never seen allergic reaction from them so they’re safe.”	7

The safety and marketing claims for the marketed interventions were typically discussed by the presenter after an emphasis on side effects of standard therapy such as open surgery. One business depicted the pharmaceutical industry as the ‘monster’ that is in control of hindering the approval of ‘natural’ therapies. The presenter offered reference to a movie called, The Good, The Bad, and The Ugly, labeling medications as ‘the ugly’, surgery as ‘the bad’ and mesenchymal SCs as ‘the good’.

All presenters claimed that a lot of research on SC therapy had been done for years, proving its effectiveness and safety. Some clinics included a list of studies on their websites, which were reviewed for purposes of this article. Referenced studies identified on some clinic websites tended to be preclinical and early phase trials needing further evidence, and some clinics listed studies for therapeutic areas that did not match the therapeutic area for which the clinic is advertising the SC therapy.

All clinics made definite, quantitative medical claims; none discussed side effects or adverse events other than some general discomfort following the procedure. All clinics presented patient testimonies or have patient testimonials available on their website or YouTube channel.

Finally, six businesses either confirmed in the presentation or on their website that their marketed interventions were not covered by insurance. The following are examples regarding insurance:

If you want quality healthcare, your insurance is not going to cover it. There is no insurance coverage for natural therapy.”

“Stem Cell Therapy is NOT yet covered by most medical insurance companies. It's thought that insurance companies will start covering SCT once more studies show results for different medical ailments. Talk to your medical insurance company to get your exact policy regarding SCT treatments.

Mention of supporting clinical evidence/ preclinical data for efficacy

Five of the seven businesses listed some studies on their websites for potential customers to refer to in order to gain knowledge on clinical evidence of SC therapies. The referenced studies seemed to be early phase trials, small sample size studies (such as a 5 year follow-up of three patients) and case reports. One business referenced a few early phase studies but mostly a long list of what appeared to be general information about SCs such as the definition of ‘blood SC’ by National Cancer Institute and a Wikipedia page on ‘regeneration in humans’.

Another business offering umbilical cord SC therapies for orthopedic diseases referenced a long list of early phase studies for embryonic, bone marrow, adipose and other source of SCs for a wide array of medical conditions, from obesity to various heart diseases, HIV-1 infections, spinal cord injuries and more. There were no therapeutic or cell source matches between the referenced studies and their marketed SC therapy.

The following quotes were pulled from some of the referenced studies mentioned on a couple of business’s websites. These quotes are being included as examples to demonstrate the early phase studies that some SC businesses cite as proof of research for patients to reference when considering the clinic’s marketed intervention.

Undoubtedly, a great deal of progress is required at both basic and clinical research fronts before these cells can be used routinely in the clinic for treating patients with osteoarthritis.”

“Although a growing interest for biological alternatives of treating knee pathology has been observed in the past few years, there still remains a paucity of high-quality studies.

Discussion

This article reports on primary data collection, which combines analyses of websites and presentations by SC businesses. The goal was to build on the few published SC seminar reports as well as the various published analyses of SC clinic websites available to date [11,19]. Consistent with these works, we found that the portrayal of SC therapies by DTC SC clinics may be overly optimistic and not properly supported by clinical evidence or substantiated by peer reviewed literature. The referenced data seemed to be early phase trials, small sample size studies, case reports and basic definitions of SCs.

This study examined whether a comprehensive review of information presented at such various SC seminars confirm consistent findings with the single seminar reports available to date. “I believe that such stem cell clinic marketing poses a significant threat to public perception and understanding of the legitimate stem cell translational medicine field,” says cell biologist Paul Knoepfler in a report sharing his first-hand experience attending an ‘educational’ SC seminar in which he described as “the stem cell hard sell” [20]. Similar observations and conclusions were also found in another seminar report titled ‘I Went to a Stem Cell Sales Pitch Seminar and I feel Like Buying a Time Share’ reported by Jonathan Jarry, McGill University’s Office for Science and Society [21]. An investigative reporter for CBS Los Angeles, David Goldstein, filmed a seminar where the ‘institute’ told the reporter that the treatment was FDA approved [22]. This is in an environment where the approximately 50% of the public believe that they have a right to try unregulated therapies [23].

Our observations confirm Knoepfler’s sense that he expressed in the following statement: “While I do not know what other stem cell clinic infomercial seminars are like first-hand, my sense from watching clinic marketing videos, including those on YouTube, is that the one I attended was fairly representative of what goes on at such customer recruitment events” [20]. Knoepfler reported first-hand his experience attending an SC seminar in which he described as having felt more like “attending a persuasive entertainment show or something on a television shopping network than an educational seminar.” Specifically, the medical claims made by the speakers at the seminar included: SCs are like a relative or an uncle in a family who is known as ‘Mr. Fixit’ to mean he/she can fix anything, and implying SCs have the power to do so; no observed side effects to the offered therapy, as well as a report of 50% improvement or better in 90% of their patients; and speaker describing their therapy as being similar to a ‘new car’ indicating no risk of immunorejection.

We have noted key observations among the SC presentations in this study. First, common recruiting strategies are used in which regular presentations are hosted by the SC clinics where the promise of SC therapies are hyped up with the strong implication that they have been well researched and proven. Oftentimes, outright safety claims are made stating that the marketed therapy is ‘safe’ with ‘no side effects’ other than common minor post procedure symptoms. None discussed any major side effects of SC therapy. Second, the risks of standard therapies are emphasized and contrasted with the ‘safety’ and convenience of SC therapy. Third, assurance of cell quality and safety of allogeneic cell sources is often discussed using the argument that the cell injections are obtained from FDA-regulated labs, or, if regulated labs are not mentioned, obtained from hospitals that ‘screen and test’ the donated cells for safety. However, the regulation of the actual SC therapy being offered is often not discussed or said to be allowed under FDA’s minimal manipulation guidelines. The assurance and safety of autologous cell sources is usually discussed by using the argument that they are the patient’s own cells and pose no risk for infection or rejection. Finally, the fourth observation relates to the common responses as to why insurance companies do not yet cover SC treatments. Often, the reason given is quality care is not covered, or insurance companies take a long time to ‘get on board’. But one business implied that ‘big pharma’ hinders the approval of ‘natural therapies’ under insurance plans.

Under very limited exceptions, where SC therapies are minimally manipulated and for homologous use, the treatments in question may be exempt from FDA oversight. However, due to the abuse and misinterpretation of what constitutes ‘minimal manipulation’ and ‘homologous use’ of cells, the FDA released guidance to clarify this criterion. Homologous use as defined by the FDA, means “the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor (21 CFR 1271.3(c)), including when such cells or tissues are for autologous use” [24]. For example, treating a burn wound by removing skin and transplanting it to cover the wound area is considered homologous use by the FDA. However, removing fat tissue from a patient’s thigh, isolating adipose SCs from the sample, then injecting these cells into an elbow that is experiencing joint pain is a procedure that shifts the biological tissue from location A to location B and purpose 1 (energy storage or insulation) to purpose 2 (pain relief). Such a procedure could be infringing on the FDA Industry Guidance since it is isolating cells from structural tissue to produce a cellular therapy for another tissue or function.

Business E was unique in their communication on their marketed interventions among the other clinics we reviewed as they marketed their intervention as an ‘exosome treatment’. The exosomes were said to be derived from SCs. As quoted by business E clinic’s website: “Our therapy uses exosomes excreted from mesenchymal stem cells derived from the umbilical cord, not the actual stem cells, as research has shown greater beneficial outcomes from exosome over stem cells with minimal risk. Exosomes used in our clinic are obtained from human umbilical cord stem cells.”

Exosomes are believed by some to have a lower risk profile than direct SC therapies, given their lack of ability to replicate; but exosomes also remain unproven as treatments and need to be carefully studied for their safety and efficacy. The FDA has not approved any exosome products for any use according to a public safety notification on exosome products by the FDA published in December 2019. In this same announcement, the FDA warned consumers about unapproved exosome products without any clear medical benefit [25].

In 2019, the FDA also issued a warning specifically about SC therapies. In its warning, the FDA advised anyone considering SC therapy to ask if the marketed treatment has been reviewed by the FDA, request facts and ask questions regarding signing a patient consent form, IND applications and IRB involvement [26]. Many US SC providers advertise interventions that are unapproved by the FDA, and recruit patients by listing their studies on ClinicalTrials.gov as ‘pay-to-participate’ studies. Pay-to-participate may exploit study subjects, as well as hinder fair selection of subjects for a robust clinical trial design that emphasizes inclusion/exclusion criteria for enrollment [27]. Further, someone considering SC therapy should note that simply because the SCs are their own cells does not mean the treatment is safe. There remain safety risks with autologous treatments; cells removed and manipulated bear the risk of cell contamination, as also warned by the FDA [26].

Preliminary data on DTC SC clinics include online content analysis of SC clinic websites, such as one conducted in 2016 which identified 570 clinics across the USA engaged in DTC marketing of SC therapies [28]. This analysis identified business locations, web addresses, types of SCs advertised and diseases/illnesses/injuries treated by the SC clinics. Indications for treatments among the identified clinics included a wide range of diseases, such as various neurological disorders, cosmetic applications, orthopedic injuries, degenerative, immunological, and pulmonary conditions, cardiovascular disorders and more. Turner and Knoepfler state that the claims made by the identified clinics “raise significant ethical issues given the lack of peer-reviewed evidence that advertised stem cell interventions are safe and efficacious for the treatment of particular diseases,” and that many of the interventions were not found to fit the criteria set by the FDA regarding “homologous use and minimal manipulation of cells and tissues” [7,28].

To date, studies examining information presented in SC presentations hosted by private SC clinics are uncommon. For that reason, we set out to perform a rigorous, quantitative assessment of an array of presentations to better understand the consistency of claims made among DTC SC clinics. This study is an attempt to determine the level of regulatory oversight of the advertised SC therapies and evaluate the quality and accuracy of information provided to patients via presentations hosted directly by the private SC businesses.

We note that some DTC SC businesses were reported to authorities as using the COVID-19 pandemic as a business opportunity, claiming that SC interventions may strengthen the immune system, prevent or even treat the COVID-19 virus. One business in our review was indicted by the FDA for using the COVID-19 pandemic to bill insurance companies for treatments to prevent the virus (albeit these treatments did not involve SCs). Turner reported on some SC businesses that have claimed to treat or prevent the COVID-19 virus [29]. One issued a press release stating, “Now Offering Mesenchymal Stem Cell Treatments to Support Lung Health During COVID-19.” Another marketed its SC interventions as a ‘precautionary measure’ to prevent the COVID-19 virus, and a third business marketed their SC intervention via Facebook stating in their post, “Did you know that STEM CELLS can be administered intravenously and by inhalation through a nebulizer to treat lung damage caused by COVID-19 and other non-related lung conditions.” In brief, it appears that clinic claims like the ones shown in the results of this article are now being tailored to ‘fit’ the current situation of the COVID-19 pandemic [30].

Our review is not to diminish or undermine the promise and potential benefits of SC therapies being studied and reported on in substantiated peer reviewed literature. Rather, we mean to attract attention to the mushrooming of SC pseudoscience for unproven, unregulated and potentially dangerous DTC SC therapies. We acknowledge the former and ongoing clinical trials which are offering SC therapies that are approved for investigational study by the FDA and IRB.

The original submitted draft of this manuscript included the business names, to permit reviewers to verify our analyses and to inform consumers. Although one reviewer requested that we keep the business names in the published version and we intended to include the name of each business to better educate consumers about the market, we had reservations about potential retaliation. Several publications in this domain do not mention businesses by name (in part to protect from frivolous lawsuits, Turner, personal communication, 2 September 2021). The publisher pointed to their disclaimer whereby “…the data and opinions that appear in the journals are the responsibility of the contributor concerned. Accordingly, the Publisher… accept no liability whatsoever for the consequences of any inaccurate or misleading data, opinions or statements.” We analyzed the situation in a series of comprehensive discussions among ourselves, with the journal and with senior counsel and administrators at UC Irvine. We have identified findings that indicate a generalizable problem. The conclusion having been established, it was not necessary to invite harassing litigation from potentially aggrieved DTC providers. Interested readers can determine, by the use of internet search engines, if these or other similar DTC SC clinic online seminars in their own geographic areas fit into the patterns we describe.

Conclusion

None of the SC therapies advertised by DTC clinics reviewed were supported by proper clinical evidence nor substantiated by peer reviewed literature. SC treatments by all seven clinics did not appear to be FDA approved or being investigated under an IND application, nor covered by insurance. Our findings are consistent with the single seminar report by Knoepfler [20]. The rising number of for-profit SC clinics in the USA advertising unproven and potentially harmful SC therapies necessitates the need for further regulatory measures and precautions in order to reduce or eliminate the risk that DTC SC clinics pose on patients’ health and on the field of SC research.

Summary points.

• Approved clinical trials are not the same as approved therapies. A US FDA-approved clinical trial indicates a therapy is approved to be tested on patients who fit the inclusion criteria set out in the associated clinical trial protocol. The outcome of the therapy offered to all the patients during the clinical trial is reviewed by the FDA and the therapy then either becomes an approved, licensed therapy or not, as determined by the FDA.

• This study examined whether a comprehensive review of information presented at various direct-to-consumer (DTC) stem-cell (SC) seminars concur with findings from the single seminar reports available to date.

• Outright safety claims are made by DTC businesses stating that the marketed therapy is ‘safe’ with ‘no side effects’ other than common minor post procedure symptoms.

• No DTC SC seminars discussed any major side effects of SC therapy.

• None of the SC therapies advertised by DTC clinics reviewed were supported by clinical evidence nor substantiated by peer reviewed literature.

• SC treatments by all seven clinics did not appear to be FDA approved or under formal investigation via an investigational new drug application, or covered by insurance.

• The rising number of DTC for-profit SC clinics in the USA advertising unproven and potentially harmful SC therapies necessitates the need for further regulatory measures.

• Surveying patients who have undergone treatments with private, DTC clinics to gain insight on their experience may compliment the results of this review.