Dubious Stem Cell Clinics

Introduction


Hallmarks of pseudoscience often involve hijacking words and concepts from cutting edge research and then making claims that go far beyond what is warranted by our current level of knowledge. Many charlatans use these claims to market products and services to an unsuspecting public.


In the late Nineteenth Century, the term "Magnetic" was popular and used by many would-be healers (such as D.D. Palmer). Flash forward a century and the word "Quantum" is widely misappropriated by cranks who likely have no idea about Quantum Mechanics (such as Deepak Chopra).

"Stem Cell Therapy" -- a term that many have heard on the news -- is the subject of cutting edge research in laboratories around the world. There has been some real progress in the treatment of certain conditions, such as in the repair of damaged corneas.

Stem cells are the cells that can self-renew and can differentiate into other cells. They are present in many tissues throughout the body. Current research is focusing on the use of stem cells as replacement therapy (to replace damaged or lost tissue), to modify the behavior of other cells, to act as targets of drug therapy, and to generate differentiated tissue for laboratory study of disease models.

There is a myriad of conditions for which stem cell treatment is under investigation. However, as of 2018, the only legitimate stem cell treatments used in clinical practice are in bone marrow transplantation, burn treatment, bone grafting in orthopedics and corneal generation from limbal stem cells in ophthalmology. And of those, only bone marrow transplantation in cancer patients has a consensus from large scale clinical trials. There currently are no other legitimate treatments that are warranted for general use by current science. We simply are not at that level.

George Daley, MD, PhD, a member of the Harvard Stem Cell Institute’s executive committee and past president of the International Society for Stem Cell Research, added,

“we are seeing a growing number [of legitimate clinical trials] but all such uses are experimental ... and there is great skepticism as to whether we have” the scientific knowledge and basis even to “predict that these will be effective.” “It may,” he said, “take decades before there is certainty.” “The only stem cell therapies that have been proven safe and effective,” he said, “are those constituting what is known as bone marrow transplantation for treatment of some cancers.”

However, such limitations do not prevent contemporary snake-oil salesmen from selling dubious treatments to desperate people by making unwarranted claims about stem cell therapies. "Stem Cell" is the new "Magnetic" and "Quantum" in the world of quackery.

As with many scams, it is sold using "sciency" words and riding on the coattails of legitimate science.

"Like snake oil salesmen, clinics claiming astonishing curative results from stem cell treatments often do not have licensed physicians administrating the treatments, no scientific evidence supporting their work, and they rely on testimonials for advertising and promoting the value of their product." 





History of Stem Cells


The presence of regenerative master cells has been hypothesized since the early twentieth century. After World War ll, interest accelerated as the threat of nuclear war raised concerns of dealing with radiation injury.


In 1963, researchers in Toronto discovered bone marrow cells that could replace all the blood cell lines. They found that injecting these cells into lethally irradiated laboratory animals could restore bone marrow function and the production of platelets, red and white blood cells.

Over the next two decades, bone marrow diseases like leukemia were being treated by first destroying the diseased marrow, and then infusing bone marrow stem cells back into the patient to restore normal function.

In 1975, cultured skin cells from a teratoma were used to generate large numbers of cells to provide cutaneous barriers in burn victims.

Research has been ongoing. Embryonic stem cell lines have been created for research purposes. For all intents and purposes, these lines are amortal as they can divide indefinitely and give rise to many specific types of cell lines. They were derived from human embryos.

In the United States, Executive Order 13505 was implemented in 2009 which prohibited the use of federal money for the creation of additional embryonic stem cell lines. As of 2018, 378 embryonic stem cell lines exist for research.

Other methods are being developed to convert adult cells into stem cells.


In 2006 in Kyoto, Japan, Sina Yamanoka successfully transplanted genes from a stem cell into an ordinary adult cell. This caused the adult cell to behave like a stem cell in that it could reproduce seemingly indefinitely and give rise to specialized adult cells. Such induced stem cells were made from fibroblasts with the use of a retrovirus. This process (called “reprogramming”) creates “induced pluripotent stem cells” (see below).

In 2012, Sina Yamanoka won the Nobel Prize for his work.

Since then, other techniques for developing induced stem cells have been researched. Chemical induction has been tried to mimic transcription factors. Protein-induced pluripotent stem cells have been created as well.

In 2013, a small proof of concept trial was published in Lancet entitled “Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomized placebo-controlled trial”. In 10 patients (13 enrolled, 3 excluded), stem cell enriched fat grafts seemed to work better than non-enhanced grafts. This has positive implications for areas such as breast reconstruction and other plastic surgeries.


In 2014, a promising technique called “stimulus-triggered acquisition of pluripotency” was described in Japan. This technique used an acid to induce the production of stem cells. However, the research data was found to have been falsified. The lead researcher committed suicide after the revelation.

In 2015, a study was published in the Lancet by Schwartz et al entitled “Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies”. The study consisted of 18 patients, 9 with macular degeneration and 9 with macular dystrophy. After a mean follow-up of 22 months, 13 of the patients showed microscopic evidence of a response and 10 of the 18 demonstrated better vision. The authors stated,

“The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease. Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement.” 

Research is actively being done in the areas of blood diseases, burns, bone grafting, retinal disease, cornea disease, Parkinson’s Disease, Huntington’s Disease, spinal cord injuries, heart attacks, and Type 1 Diabetes. These studies have so far been in mice and rats. Some phase 2 trials are underway. Proper phase 3 human trials have not been done as of 2018.

As stated above, stem cells have only been proven for clinical use for blood disorders. Promising work is being done in other areas.

It is a exciting field, but nowhere in the science of stem cells can justification be found for the miraculous and outrageous claims being made by the numerous dubious “stem cell clinics” found proliferating all over the world.

 




Types of Stem Cells


We can categorize stem cells by their “potency”, or their ability to differentiate into other cells.



Totipotent stem cells can give rise to all the cells of the body as well as the placenta that supports the body during embryonic development. Thus, they are both embryonic and placental. Totipotent cells are the initial cells of a dividing fertilized egg prior to implantation, collectively called a blastocyst.

Pluripotent stem cells are embryonic. They cannot give rise to placental cells but can differentiate into all the cell lines (called “germ lines”) that make a body.

Germ lines include the endoderm (which forms organ linings), the mesoderm (which forms muscle, bone, cartilage, fat and connective tissue), and the ectoderm (which forms nerves, skin and tooth enamel).

Multipotent stem cells can give rise to all cells within a given germ line but not others. Mesoderm cells cannot differentiate into ectoderm cells, etc.

Unipotent stem cells can only generate one cell type within a germ line.



We can also categorize them by their source of origin.

Embryonic stem cells are harvested from embryos.

Adult stem cells (also known as “somatic stem cells”) can be harvested from the tissues of children or adults. They tend to be multipotent or unipotent. Commonly, “mesenchymal” stem cells (from mesodermal origin) are the adult stem cells used in research (and supposedly in practice – but we’ll get to that later).

Note that “adult stem cells” are not the same as “adult cells”. Adult cells are simply just normal cells. They do not differentiate further and have limited or no ability to divide.







Translational Hurdles


Scientific medicine progresses slowly.


After basic science bench research identifies a potential for a type of treatment, clinical research then proceeds in phases.

These are defined as phases 1 – 4.

• phase I: safety, tolerability, pharmokinetics, pharmodynamics. Usually involves ramping doses.

• phase II: expanded version of phase I, IIa for dosing, IIb for efficacy.

(When drugs fail, they usually fail in phase II.)

• phase III: definitive, hence expensive assessment of efficacy, typically double-blind, necessary for a regulatory submission.

• phase IV: post-launch surveillance, rarer adverse effects detected here.

With few exceptions, the current state of stem cell science is mainly limited to phase 1 and 2 trials.



A 2018 special report in the New England Journal of Medicine states,

“Despite a proliferation of early-phase trials of mesenchymal stem cells, definitive studies regarding the safety and efficacy of such procedures as compared with the standard of care have been lacking.” 

There are many concerns and hurdles to overcome.


Collectively, the problem is “translation”. How can we the actual translate our current understanding of stem cells into usable therapies?

Yeild. One practical problem with translation is low yield. Current methods of obtaining these cells have relatively low yield. It has proved difficult to harvest enough cells for most potential clinical applications. This makes research difficult. Low yield harvesting techniques also will limit wide-spread legitimate use even it such treatments pass phase 3 trials.

Homing. The next translational issue is “targeting”, also known as “homing”. How can we get a stem cell to the exact desired place in the body? If we do manage to get the cells to the desired place, how can we get the cell to behave in the way that we wish? Despite the endless claims on clinic websites, stem cells don’t just “know” what to do as if by magic.

Proving efficacy. Even if we develop high-yielding harvesting methods, and even if we can get the cells to the desired targets, will there be enough positive and measurable effects from the treatment. Many trials have been very disappointing. For instance, trials involving patients with ischemic heart disease have failed to show significant results. Ongoing trials for non-ischemic heart failure have shown more promise but have suffered from discrepancies. As of 2018, stem cell therapy for heart disease has been disappointing.

Safety. Most importantly, we have to prove safety. A huge concern about stem cell treatments is tumorigenicity. Cancer cells are just cells that replicate without restriction, usually to the detriment of the patient. Stem cells can replicate indefinitely as undifferentiated cells. It would seem that a major trick to master would be getting the cells to do their jobs (repairing or replacing aging or diseased tissues) without becoming a cancerous tumor.

Legitimate stem cell researchers concern themselves with these challenges and more.

Today’s plethora of dubious stem cell clinics offer a multitude of unproven, likely useless, expensive and potentially dangerous treatments.

The “doctors” of these clinics do not seem concerned in the slightest about such challenges. 




Stem Cell Quackery – the New “Quantum”

One of the dangers facing the legitimacy of stem cell therapy is the rapid rise of non-legitimate stem cell clinics around the world. As of 2018, the phrase “stem cell” is used to sell dubious and potentially dangerous untested treatments to desperate patients for high prices. The peddlers of these treatments point to the growing and promising field of stem cell research as if it is a body of evidence to support outrageous cure-all claims to the unsuspecting public.

Peddlers of pseudoscience often focus their claims to the mysterious sounding science of the day. For centuries, “magnetic healers” sold treatments using magnetism to heal just about any ailment under the sun. Animal magnetism was a term coined by Franz Mesmer to describe the body’s natural magnetic field and the potential for healing our ailments by its manipulation. Magnetic healing became popular but never proven. The words “magnet”, “field” and “energy” tap the imagination of the public. As most people even today do not really understand the meanings of these words, we tend to be lured by those who claim to not only understand them, but to harness their power to heal. Indeed, the inventor of Chiropractic, D.D. Palmer was a “magnetic healer”.

Other mysterious scientific concepts have become fodder for pseudoscientists. Quantum mechanics is one of our most successful scientific theories about the bazaar atomic and subatomic world. Yet no one understands it, at least not really. Physicist Richard Feynman famously stated, “
If you think you understand quantum mechanics, you don't understand quantum mechanics.”


“Quantum” has been hijacked by pseudoscience peddlers to sell many products, services, books and seminars. A Google search for “quantum healing” reveals over 1.5 million citations. At the forefront of the quantum healing empire is Deepak Chopra, a former endocrinologist. The Wikipedia page for Quantum healing states, “The term was coined by Deepak Chopra. His discussions of quantum healing have been characterized as technobabble - "incoherent babbling strewn with scientific terms" which "drives crazy people who actually understand physics" and "redefining Wrong".

In the Huffington Post, Chopra stated,

“It was only with the advent of quantum physics that scientists began to consider again the old question of the possibility of comprehending the world as a form of mind. Indeed, the quantum theory implies that consciousness must exist, and that the content of the mind is the ultimate reality”. 

Mysterious and misunderstood subjects such as magnetic, energy, quantum spark our imagination. Potential exists in these sciences, but only the experts understand them. Now we add “stem cell” to the list of buzzwords that capture desperate consumers’ attention.

In addition to expensive seminars and treatment programs, “stem cell therapy” has become big business. In 2016, a study conducted by Leigh Turner and Paul Knoepfler found that 351 companies in the United States were producing stem cell products for 510 clinics (more on that below). That’s a lot for a technology that has never been through phase 3 clinical trials (apart from bone marrow transplantation). These clinics appear to be clustered in Southern California, Florida and the north-eastern states.


With the promise of what sounds like a magic technology, these clinics offer treatments for conditions across a wide range including orthopedics, pain management, neurologic problems, immune diseases, respiratory diseases, urologic, sexual, cosmetic, cardiovascular and dermatologic disorders. They advertise treatments for aging, diabetes, hair loss, muscular dystrophy, vision problems, gastrointestinal disorders, Alzheimer’s and autism.

Products are on sale now promoting magical-sounding claims of skin rejuvenation with the words “stem cell” attached to their names. Many products promote plant-based stem cell creams (yes, you read that correctly). One company’s advertisement claims, “(our) cutting edge technology brings an innovative anti-aging skin care line. Plant stem cells are the source of unlimited energy and the key to herbal growth and regeneration”.

Many sites use the language of pseudoscience to make specific-sounding claims, but in reality, are vacuous. Motor City StemCell claims that their products “Control the immune system”, “regulate inflammation” and “provide trophic support”. The operative words here are “control”, “regulate”, and “supports”. Skeptics recognize these as “weasel words”. They do not make specific claims for which the claimants may be held to account. Other weasel words include “boosts” and “enhances”.

When such words are used, often they are accompanied by the Quack Miranda Warning:

“These statement(s) have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.” 

The tactics of selling snake oil have become sophisticated over the years, but the overall strategy has remained the same. Find vulnerable customers (“marks”); make bold claims of a “cure for everything”; claim 100% safety and efficacy; use sciency-sounding technobabble; point to legitimate research as if it supports your claims; promote testimonials from happy customers; charge high fees for unproven or implausible products and services; attack your critics as being closed minded, or in the pocket of “Big Pharma”; repeat.





Stem Cell Tourism


In the early 2000’s, the first reports of unsubstantiated stem cell services emerged in the U.S. and Europe. People were eager to use what they perceived to be cutting-edge science and were frustrated by the slow progress of legitimate science. As there have been few legitimate treatments based on stem cells available, charlatans (looking to exploit the publics’ limited knowledge of the emerging science) began marketing such treatments directly to the public over the (then new) internet.


In 2001, the Bush Administration ended federal funding for the creation of new embryonic cell lines. Federal law enforcement also shut down a couple of stem cell companies in the U. S. and prosecuted the owners. 

A 2006 FBI report stated:

“U.S. District Judge Gray Miller sentenced Lawrence Stowe, 61, a total sentence of 78 months in federal prison to be immediately followed by three years of supervised release. In handing down the sentence, Judge Miller emphasized that Stowe “…took advantage of people dying and offered them hope.” Restitution was also ordered in the amount of $419,358 to be paid jointly and severally with co-defendant Francisco Morales, 54, of Brownsville. Morales was previously sentenced to 60 months in prison.


Stowe, of Moline, Illinois, admitted that beginning in January 2006, he utilized several businesses, Stowe BioTherapy Inc. and The Stowe Foundation to advertise and promote a medical treatment protocol for the treatment of amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease, multiple sclerosis (MS), Parkinson’s, and other neurological diseases. This treatment protocol, which was named “Applied Biologics,” consisted of supplements, vaccines, patient specific transfer factors and ultimately stem cell therapy. Stowe falsely represented to patients that this treatment protocol had been reviewed by all levels of the FDA and was effective in the treatment of ALS, MS, and Parkinson’s. There is currently no cure for these diseases.” 


Regulatory hurdles in the United States and similar nations led the charlatans to set up shop in countries with little to no oversight. With the benefit of the internet, they could send their unsubstantiated claims into the world to attract desperate customers.

“…a second wave of stem cell marketing operations emerged. These businesses, which were often based in developing economies, targeted both local residents and patients from wealthier nations, giving rise to what became known for a time as “stem cell tourism”. Such businesses offered cell-based or tissue-based procedures, sometimes targeting more than 100 different medical conditions, at prices of tens of thousands of dollars per treatment course. Due to vague or non-existent regulation, or lax enforcement, numerous such companies remain in operation in countries, such as Mexico, India, and Thailand.” (from The malignant niche: safe spaces for toxic stem cell marketing



In a 2015 JAMA Neurology article, Bowman, et al, describe the industry:

“Stem cell tourism is a rising Internet-based industry that aims to offer unproven procedures to patients with incurable diseases. This unregulated activity is reaching the neurologist’s office as well as across the world, as patients request information or clearance for such procedures. Herein, we posit the need for medical societies and licensing boards to bring this issue to the forefront of neurology because it has the potential to affect patient care with risk of morbidity and mortality, as well as to undermine public confidence in legitimate stem cell research for incurable neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis.”


A 2016 cautionary article in the New York Times also described the practice.

“A growing number of clinics, often in places like Russia or China, but also in Europe and elsewhere, say on websites that they can treat, even cure, diseases like muscular dystrophy, Alzheimer’s, Parkinson’s, and spinal cord injury as well as strokes, by injecting patients with stem cells that, in theory, could develop into a missing nerve, a muscle or other cells and repair damage from an illness or an injury." 


Reports by injured athletes of seemingly miraculous results have contributed to a growing interest among desperate patients. Estimates are that tens of thousands of patients around the world have had such treatments and that the industry is worth hundreds of millions of dollars.



The clinics, which are unregulated, have websites with glowing testimonials from patients, some of which… have financial interests in the clinics. The clinics often claim to be doing clinical trials, giving a veneer of legitimacy to their work.”

The article describes a gentleman named Jim Gass, a 66 year old lawyer who suffered a stroke and was looking to cure his left-sided paralysis with stem cell injections.

“Mr. Gass, it turned out, had had stem cell therapy at clinics in Mexico, China and Argentina, paying tens of thousands of dollars each time for injections in a desperate attempt to recover from a stroke he had in 2009. The total cost with travel was close to $300,000.” 


Mr. Gass soon developed intractable pain and loss the use of his legs. It was then discovered that he had developed an inoperable tumor of the spine. The tumor cells were composed of “nonhost cells”. In other words, the tumor did not come from his own cells. They were somebody else’s.

His case was reported in the July 14th, 2016 edition of the New England Journal of Medicine. It states:

“…the infusions were described as consisting of mesenchymal, embryonic, and fetal neural stem cells. Progressive lower back pain, paraplegia, and urinary incontinence subsequently developed. Magnetic resonance imaging (MRI) revealed a lesion of the thoracic spinal cord and thecal sac; a biopsy specimen was obtained.Neuropathological analysis revealed a densely cellular, highly proliferative, primitive neoplasm with glial differentiation. Short tandem repeat DNA fingerprinting analysis indicated that the mass was predominantly composed of nonhost cells.” 


The pathology and MRI images can be viewed here. Mr. Gass became paralyzed from the waist down.


Another case that received media attention was that of hockey legend, Gordie Howe.



Known as “Mr. Hockey”, he was a beloved player for the Detroit Red Wings. In 2014, at age 86, Mr. Howe suffered a debilitating stroke leaving him paralyzed on the right side. 

He survived. But after suffering a setback, he and his family travelled to Tijuana, Mexico to receive stem cell treatments from a clinic called Santa Clarita, which is run by another company called “Novastem”. The cells were produced by a California company called “Stemedica”. The cells were donated free of charge by Stemedica. . 

David Gorski, MD, reports that Stemedica has registered a clinical trial for stem cell therapy for stroke . However, Novastem was not listed as a participating center in the clinical trial. Novastem’s website claims to treat many ailments such as stroke, traumatic brain injuries, heart disease, arthritis and even aging.

After receiving his treatment in Tijuana, conflicting stories emerged about Mr. Howe’s progress. His daughter claimed that he was walking independently within days. His son stated that he was taking some steps and working on speech. The Detroit media reported on his remarkable response.

It is unclear if he was actually improving beyond what one might expect given enough time after a debilitating stroke. Gordie Howe died at age 88, within two years of his stroke.

With highly publicized cases like Gordie Howe’s, demand for stem cell therapy increased.

The evidence for it has not.




Dubious U.S. Stem Cell Clinics (and how they get away with it)


In the years following 2010, more and more so-called stem cell clinics have begun advertising within the United States. The actual number is changing. A quick Google search for stem cell clinics in the United States yields millions of hits for what is likely thousands of clinics.

In a 2016 study entitled “Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry” by Leigh Turner and Paul Knoepfler, they found “351 U.S. businesses engaged in direct-to-consumer marketing of stem cell interventions offered at 570 clinics.

This is big business. Clinics typically charge between $2,000 to $100,000 for treatment for a range of ailments that are limited only by one’s imagination. They target desperate patients who may have to spend their retirement savings or tap the generosity of friends and family to fund their miracle treatments.

In the United States, clinics are supposed to adhere to the regulations that define how products and services are to be used.

A review of the federal regulations concerning biologic products appeared in the March, 2018 New England Journal. (Note: HCT/P refers to “human cell and tissue products,” a defined subset of which are regulated as biological drugs by FDA)

The decision regarding which regulatory pathway a given product must follow rests in part on whether the product meets or does not meet the criteria of the regulations promulgated under the Code of Federal Regulations part 1271 of Title 21, which have been in place since 2005.

In brief, products that are regulated solely under Section 361 generally are those that :

·         do not undergo substantial processing (minimal manipulation),

·         are used in a manner in the recipient that is similar to that in the donor (homologous use),

·         are not combined with another drug or biologic product, and

·         do not have a systemic effect, unless they are designed for autologous transplantation, first- or second-degree–related allogeneic transplantation, or reproductive use.

 Examples include corneas and heart valves. Such cells and tissues are subject to FDA regulations only to prevent the transmission of communicable diseases.

All other HCT/P products are regulated as drugs, biologics, or devices and require appropriate regulatory submissions for the conduct of clinical trials and marketing.”

 

One key to the industry’s growth has been the exploitation of a once obscure provision in the federal code, CFR 1271.15(b), known as the “same surgical procedure” exception:

“You are not required to comply with the requirements of this part if you are an establishment that removes HCT/P’s from an individual and implants such HCT/P’s into the same individual during the same surgical procedure”

So, if stem cell clinics use products that are “minimally manipulated”, are extracted and given back to the same patient, are not combined with drugs and do not have a “systemic effect”, then the FDA will not regulate the products and services as “drugs”. The FDA’s only oversight is the prevention of infections from the procedures. Some of the stem cell procedures provided by U.S. clinics are then exempt from FDA regulations. Many are clearly not.

Many clinics advertise commercially available products that clearly do not come from the patient and have been processed. 

“MotorCity StemCell” claims

“OUR CELLS ARE BETTER THAN YOURS! Amniotic derived MSC are preferable to adipose based tissue for musculoskeletal regeneration.”

They buy a commercial product from a company that claims to prepare amniotic mesenchymal stem cells from volunteer expectant mothers. Clearly, this does not qualify for an FDA exemption.


Since there are FDA rules against such treatments, typical U.S. clinics have developed various modus operandi.

Many use something we may call the “Clinical Trial Ruse”. Taking a page from Stanislaw Burzinski, some U.S. stem cell clinics operate under the guise of conducting clinical trials. Many register such trials on ClinicalTrials.gov. They then charge desperate patients to participate in their “studies”.

An article in Forbes by Stephen Salzberg describes the practice:

"In recent years, companies offering questionable stem cell therapies got the bright idea that they could describe their treatments as clinical trials, register them on ClinicalTrials.gov and thereby get some free advertising. Most stem cell treatments are not FDA-approved, and many have little or no data supporting their effectiveness, but clinics can still register their "trials" on the NIH site, making it appear that they are supported and endorsed by the government."

"What's especially worrisome is that some stem-cell treatment clinics charge patients very high fees to participate in their "trials." Some patients (perhaps most) don't know that legitimate clinical trials virtually never charge fees."

"Most patients think, mistakenly, that if a clinic offers stem cell therapy, it must have been approved by the FDA. That's not true–clinics offering these therapies don't have FDA approval, and they argue that they don't need it (which might be correct, 
but that's a topic for another day)."

"Patients also assume that trials listed on ClincialTrials.gov must have been approved by some government agency, but that's not true either. The site is a clearinghouse that uses the honor system, nothing more, to ensure that trials listed there are legitimate. If you read its disclaimer (but who does?), you find that studies listed on the site are not necessarily funded by NIH or approved by the FDA. What these stem cell clinics are doing is not a clinical trial, and advertising their services through ClinicalTrials.gov is reprehensible. For now, if a doctor or clinic tries to charge you to participate in a clinical trial, your best course may be to find another trial–and another doctor."

 

Stem cell researcher and author of The Niche blog, Paul Knoepfler, is also concerned about the misuse of ClinicalTrials.gov.

“Dubious stem cell clinics are taking advantage of this loophole to get an air of legitimacy and often use their listing in Clinicaltrials.gov as a marketing tool to convince their potential customers that their trials are approved by the federal government (see hypothetical example below of such a web marketing approach), which at best is misleading.

Another level of strangeness to this situation is that although Clinicaltrials.gov is intended primarily to be a database for trials of experimental new drugs (keep in mind that stem cells products often are biological drugs), the dubious clinics–despite listing their “trials” on the site–claim that their stem cell products are not drugs.”


Leigh Turner wrote in 2017,

“Numerous US businesses that engage in direct-to-consumer advertising of stem cell interventions that are not US FDA-approved also recruit clients by listing ‘pay-to-participate’ studies listed on ClinicalTrials.gov. Individuals considering enrolling in such studies and NIH officials responsible for overseeing the database need to be aware that some businesses are using the registry to promote unapproved stem cell interventions that study subjects are charged to receive. Inclusion of such studies in ClinicalTrials.gov reveals that the database needs better screening tools. In particular, screening should evaluate whether studies submitted to the registry have been reviewed and permitted to proceed by the FDA in the case of clinical studies requiring FDA clearance in addition to institutional review board approval.

 With a few exceptions, clinics cannot make specific medical claims that contradict established fact. As a strategy to appear scientifically accurate, they will make matter-of-fact statements about stem cells and the about certain medical conditions.

For instance, the company “U.S. StemCell Clinic” states,

Orthopedic conditions are ailments and disorders in muscles, ligaments, and joints

and

“According to research, stem cells have self-renewal qualities which aid in the reproduction of cartilage and bone tissue cells, the restoration of joint function, and the reduction of pain.”


These statements are true. 

They then make the unsubstantiated claim,

This mean that stem cell transplants could be used to treat some of the most common orthopedic symptoms.”


Clinics therefore use “weasel words” to skirt around making actual claims while maintaining the appearance of promising the world. Notice the word “could” is conveniently inserted into the statement. No actual claim is made.

As mentioned above, infamous weasel words include “support”, “enhance”, “treat”, “help” and “boost”.

“Amirastem” uses phrases such as, “have the potential” , “may” and “can” – as opposed to “are known to”, “cures” or “does”.

Your own Stem Cells have the potential to regenerate all kind of cells of the body.  Scientists have developed the technology to differentiate Stem cells into neural cell, blood cells, skin cell and hair cells. These cells may be used to replace the old cells of body with new and young cells to treat the aging related diseases.”

and

stem cells treatment involves administration of concentrated cells in the targeted area, wherein they can colonize in the damaged area, adapt the properties of resident stem cells and initiate some of the lost functions that have been compromised by the disease or injury.


Next, clinics heavily advertise testimonials by seemingly happy patients. They offer these testimonials as their main source of “evidence”. As we know, testimonials are not evidence, but they are convincing. A known advertising technique is the promotion of celebrity testimonials.

The home page for “StemGenex” prominently features video testimonial by the wife of “Happy Days” star Donny Most (who played Richie Cunningham’s buddy, Ralph Mouth). Mr. Most has Parkinson’s Disease and his wife claims that he made progress after stem cell treatments.

By quoting people in testimonials, they give the impression that they are making scientifically valid statements. They are not.

Another common ruse (and dead give-away for pseudoscience) is the “cure for everything”. However, many U.S. stem cell clinics are careful enough not to claim actual cures. They simply state what ailments for which they offer treatments, and then claim that the treatments are “beneficial” in some way. Apparently, “beneficial” means whatever the people in the testimonial videos say.


One Michigan clinic called "The Knee Institute & Regenerative Medicine" claims the following:


Wow. Sounds almost too good to be true!

Clinics will boast about actual research being conducted by legitimate scientists. Most websites include links to articles on PubMed or scientific journals that usually describe basic science research or Phase 1 and 2 trials. None of the legitimate research referenced by these sites actually support the practices advertised or the outrageous claims made.

Some will try to baffle their potential marks with quasi-sounding claims to legitimate data. For instance, as of 2018 “The Knee Institute” claimed,

If you search www.pubmed.gov you will find 3,572 articles regarding Stem Cell Therapy. If you have any further questions, write them down for your FREE consultation and our nurse case manager will answer them for you.

Actually, as of 2018, if one were to type “Stem Cell Therapy” into Pubmed, the result yields over 14,000 citations and the reader is given over 7,000 pages to browse. Stem cell research is a legitimate field of study. The average lay person may feel overwhelmed to find such a plethora of articles. There are no legitimate articles that support many or all of the bogus claims made by “The Knee Institute”. 

 

As of 2018, the American “Stem Cell” business is thriving and cashing in.

While clinics in unregulated foreign countries depends on the internet, American clinics also lure customers with “free” seminars. These events are often held in fancy restaurants or clubs. You may get a free meal and hear a talk from an “expert” with a white coat and a fancy Power Point presentation. A sign-in list is required at the door on which the marks guests are asked to give their contact and (sometimes) their financial information. Attendees are given the hard sell-job and are told that they may get a big discount if they “act now” and “sign up”.

 

David Brafman, PhD is an assistant Professor in the Department of Bioengineering at Arizona State University who has been performing stem cell-related research for better part of a decade. 

He described his experience at one of these seminars put on by “The Lung Institute” in Arizona:



“I registered early (an hour before the start of the seminar) because according to the registration portal ‘Space is limited – Only 30 seats available.’ The seminar was held in a nice, recently built medical facility in a location in the Phoenix area that was near a retirement community. I had only expected a few other people to be in attendance but was surprised when I had arrived that it was standing room only. By my count, there were over 40 people in attendance and most, if not all, the people in attendance were elderly, many of them had supplemental oxygen, and by my guess suffering from some sort of lung disease. It would seem that these patients were subject to direct advertising methods—or worse—were referred to the clinic by their own physicians. Being there with all these patients also brought home for me in a very direct way just how many people are suffering and looking for hope. I am sensitive to their situations and wish them the best. 

The seminar began with the head of the clinic, Dr. Burton Feinerman, providing an overview of the treatment process. He did not go into specifics but stated that his clinic offered three treatment plans for suffers of lung disease (see attached informational pamphlet). All three options are similar in that ‘stem cells’ are isolated from the patient’s blood, adipose tissue, or bone marrow and delivered back to the body through the use of an IV and/or nebulizer. 

After Dr. Feinerman’s presentation, several patient coordinators shared ‘success’ stories with the audience. Each story had a similar narrative in that a patient suffering from a lung disease came to the clinic because they were out of treatment options. After receiving treatments, the patient’s status improved. In a short period of time, they were able to perform activities that they were previously unable to perform. If it works these patients, it will surely work for you! 

Finally, Elise Myers, the head patient coordinator (and former Bachelor contestant—Celebrity endorsement!), shared the next steps patients needed to take in order to sign up for the treatment. At the end of her presentation, she stated that the next round of treatments were going to begin in May. Unfortunately, they were almost fully booked. However, if patients signed up that day they would receive a $2000 discount (as an aside the treatments offered by the Lung Institute have been reported to be in excess of $10,000). Act now to take advantage of this special opportunity! 

After Ms. Myers’ presentation, Dr. Feinerman took questions from the audience. The majority of the audience members’ questions where about their particular condition and if the treatments offered by the clinic would be effective in their particular cases. Dr. Feinerman’s response was always an unequivocal “yes”.” 

During a Q&A at the end of the presentation, Dr. Brafman identified himself as a stem cell researcher and took issue with the outrageous claims being made. He was accused of not being sympathetic by the presenters, booed by the audience and escorted out of the building.

 

And finally, these clinics make claims about their products that just simply may not be true.

 “Many US stem cell clinics advertise what they describe as adipose-derived autologous adult stem cell treatments. (Because such businesses typically do not make public their clinical protocols or publish peer-reviewed data, little is usually known about exactly what types of cells these clinics administer to patients. Nonetheless, when making marketing claims, these businesses use the rhetoric of “stem cell therapies,” even though many researchers question whether patients are administered actual stem cells.)” Leigh G. Turner




Promotion of Other Quackery

In for a penny, in for a pound.

The people that charge huge fees for unsubstantiated stem cell treatments do not care that their services are likely unhelpful and potentially harmful. Since their ethics (or their beliefs) are not bound by the scientific method, why should they limit themselves to just one form of nonsense?

Just as chiropractors are likely to promote things like “megavitamins”, and as Homeopaths are likely to promote acupuncture, it should come as no surprise that stem cell clinics offer other “alternative” treatments.

“MotorCity StemCell” also promotes IV Nutrient therapy, chelation, nutraceuticals, “ozone treatment” and hormone management. They even sell “Stem Cell Cream”! 

“Stem Cell Cream has the same anti-inflammatory properties as our actual stem cell product but is formulated as a cream. Some people notice almost instant relief from using cream alone”. 

MotorCity StemCell site lists prices. “Stem Cell Cream” costs $300 and “Ozone” costs $350.




“Stem Cell Therapy Plus” sells “Stem Cell Supplements”. These are pills.

Yes, pills.

 

“Stem Cell Supplements are developed based on the merits of stem cells and they are applied for degenerative diseases treatments and to stimulate the formation of all the different tissues of the body: muscle, cartilage, tendon, ligament, bone, blood, nerve, organs, etc. Stem Cell Supplements bring essential anti-ageing, health & beauty benefits by providing necessary elements to the body to improve cellular regeneration, organ rejuvenation and tissue healing.”

 



But where do these “supplements” come from?

Their website states,


“Now the bioactive stem cells treatment is available to the public in high-tech softgel capsule form. Stem Cell Therapy Plus starts with the selection of specific organ stem cells from sheep placenta extracts. These stem cells, when orally ingested via bioactive softgel capsules, are functionally organ specific but not species specific, so they recognize and congregate at the human counterpart of the organ from which they were taken and imprint their vigor upon old, tired, and degenerating cells, stimulating them to function with renewed efficiency. The organ itself then retains its vigor and vitality, thus degenerative diseases or chronic ailments in the organ may be treated.”

 

One would be quite justified in being very skeptical.

 

“San Francisco Stem Cell Treatment Center” offers “Brain Tap Technologies”.

“Self-Mastery Technology (SMT), which is the MindFit Neuro-Trainer, a neuro-re-training to balance the brain. Using precise frequencies of light and sound waves, the patient wears specially designed headphones and glasses during each session, guiding them into a state of relaxation. Once the brain is fully relaxed, it can start to do self-adjustments. This helps the patient to reprogram their physiology and neurology to relieve stress, lose weight, sleep better, and many other benefits.”

 


The same clinic also sells “AQ Skin Solutions”.

“AQ Growth Factor Induced Therapy (GFIT) provides active peptides and proteins topically, which may stimulate the skin to rejuvenate, reducing the appearance of fine lines, wrinkles, scars, acne, and age spots.”






Disastrous Outcomes


Nearly all stem cell companies and clinics claim absolute safety. “No side effects” is a common phrase found on their websites. However, legitimate stem cell research is still in its early stages. Remember that Phase 1 trials look at safety to the extent that it may seem reasonable to advance to Phase 2 trials and beyond. True safety is studied at every step of the way. The true rate of adverse events are usually not known until Phase 4 trials have been done after a drug or treatment has been utilized in the public domain by mainstream doctors.

There is no way that any of these clinics can claim to know that their treatments are safe (let alone effective). Their evidence comes from their own anecdotal experience and the testimonies of their patients. The safety claims made by stem cell clinics are not based on proper science. If stem cell therapy is 100% safe, then we should not be see any disasters following such treatments. In fact, we do.

Indeed, when horrible outcomes happen and are made public, proponents point the finger of blame at factors other than the therapy itself.

Here are a few cases of bad outcomes that a quick online search will find.


In 2001, a 13 year old child with ataxia telangiectasia given allogenic fetal neural stem cell injections into his nervous system in Russia. He received treatments in 2002 and 2004 as well. In 2005, he developed severe headaches. He had a brain tumor originating from the donor stem cells. He underwent brain surgery in 2006. His ataxia telangiectasia was not cured.

In 2009, a woman had a “stem cell face lift” in Beverly Hills with mesenchymal stem cells and a filler called calcium hydroxylapatite for the cost of $20,000. Pieces of bone began to grow in her eyelids and around her face which required extensive plastic surgery to fix.

In 2010, a 18 month old Romanian boy died after having stem cells injected into his brain at a stem cell clinic in Germany. Three months earlier, a 10 year old boy from Azerbaijan nearly died at the same clinic from the same procedure. The doctor was under criminal investigation and “Europe’s largest stem cell clinic” was shut down.

In 2010, South Korean media reported that two patients who had received stem cell procedures in Japan and China had died, and cited allegations that the company “RNL Bio” had lured clients to clinics overseas to skirt domestic laws banning stem cell treatment. The International Cellular Medicine Society (ICMS) cleared the company siting correlation rather than causation.

In 2012, a Florida cardiologist’s license was revoked after two of his patients suffered cardiac arrest and died following the infusion of stem cells. The first patient died in 2009 during the treatment. The second in 2012.

In 2013, the Journal of Clinical Neuroscience reported

“a 27-year-old woman, who, 3 months after a devastating low cervical myelitis, underwent intrathecal mesenchymal stem cell (MSC) infusions. Six hours after the third infusion, she became unconscious, febrile and cerebral MRI showed acute bitemporal and left cerebellar lesions, consistent with an acute disseminated encephalomyelitis. It is likely that this is the first reported patient with neuroinflammatory exacerbation after MSC therapy. This case suggests that, in addition to their malignant potential, autologous MSC expanded in vitro can exhibit immune-activating properties leading to autoimmune exacerbation.”

In 2013, the Yonsei Medical Journal in S. Korea reported on a 41 year old man and his two parents who had undergone fat-derived mesenchymal stem cell infusions. All three developed “artificial” pulmonary embolisms and infarcts (fat emboli that blocked blood flow to the lung tissue, killing portions of the lungs).

In April 2013, the Annals of Plastic Surgery reported a case of a 63-year-old woman who underwent face and neck lift with autologous fat
transfer—called by her physician a “stem cell face lift.” “At approximately 4-weeks postoperative, the patient developed facial swellings, erythema, necrotizing ulcers, and an orocutaneous fistula. New lesions continued occurring up to 16 weeks after surgery.” It was diagnosed as “Necrotizing Metachronous Facial Ulcerations” and likely due to mycobacterial infection.

In 2014, the Journal of Neurosurgery: Spine reported a case of an 18 year old woman who suffered a spinal chord injury and was paralyzed. She was treated with olfactory mucosal stem cells at the site of the injury. 8 years later, she developed back pain and was found to have a tumor made of nose tissue in her spine intertwined with growing nerves. She had more surgery and remains paralyzed. 

As stated previously, in 2016 The New York Times published an article about James Gass, a lawyer who had spinal stem cell injections and later developed a malignant spinal tumor of non-host cell origin.

In 2017, a review in the New England Journal of Medicine looked at clinical trials for stem cell injections into the eyes of patients with macular degeneration. The trials were registered on ClinicalTrials.gov. Clinics in and outside of the U.S. participated. The authors looked at three patients who went completely blind after the procedures. 

                                   

“The patients’ severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients’ visual acuity ranged from 20/200 to no light perception.” 





Conclusion


Stem Cell research is a promising field. There may be a day in the future in which there are many disorders that can be effectively and safely treated with stem cell therapy. That day is not here yet.


However, we currently have many clinics across the world offering treatments under the guise of "Stem Cell Therapy". Their claims go well beyond the current science and are therefore not justified. These treatments are not regulated or endorsed by agencies such as the FDA. The consumer will pay large sums of money -- tens or hundreds of thousands of dollars -- to receive unproven, unregulated "treatments" at their own expense, often under the guise of a "clinical trial". No legitimate research organization charges participants to participate in clinical trials.

These treatments have unknown risks and unproven benefits. They are marketed with fancy websites, testimonials and expensive dinner seminars by providers -- some of whom are actual MD's or DO's and should know better -- with no regard to scientific standards or ethics. They will use scientific-style jargon and promise miraculous cures for just about anything that ails you. This is a scam.

Unfortunately, these charlatans will muddy the waters legitimate research and for future science-based treatments by legitimate providers.

This is truly a "buyer beware" situation.

For now, save your money.



John Byrne, MD




References


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Novella, Steven and MD . "Stem Cell Tourism Comes Home – Science-Based Medicine." Last modified 2018. Accessed 5 Jun 2018. https://sciencebasedmedicine.org/stem-cell-tourism-comes-home/

Parker, Graham, Ph.D., Loring F. Jeanne and Ph.D. . "Protect Stem Cell Science from Stem Cell Quackery Keep the Opportunities, Lose the Opportunists ." Last modified 2016. Accessed 5 Jun 2018. https://www.genengnews.com/gen-articles/protect-stem-cell-science-from-stem-cell-quackery/5820

Barrett, Stephen and M.D. . "The Shady Side of Embryonic Stem Cell Therapy." Last modified 2015. Accessed 5 Jun 2018. https://www.quackwatch.org/06ResearchProjects/stemcell.html. Salzberg, Steven. "Stem Cell Clinics Are Advertising Their Treatments As Clinical Trials. They're Not." Last modified 2017. Accessed 5 Jun 2018. https://www.forbes.com/sites/stevensalzberg/2017/07/24/stem-cell-clinics-are-advertising-their-treatments-as-clinical-trials-theyre-not/#77940ba96b03

Turner, Leigh and Knoepfler Paul. "Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry." Last modified 2016. Accessed 5 Jun 2018. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)30157-6

McGinley, Laurie and Wan William. "Miracle cures or modern quackery? Stem cell clinics multiply, with heartbreaking results for some patients. - The Washington Post." Last modified 2018. Accessed 5 Jun 2018. https://www.washingtonpost.com/national/health-science/miracle-cures-or-modern-quackery-stem-cell-clinics-multiply-with-heartbreaking-results-for-some-patients/2018/04/29/80cbcee8-26e1-11e8-874b-d517e912f125_story.html?utm_term=.f558ec59dd91

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Russo, David. "Columbia Pain Management's David Russo on why patients should beware of stem cell quackery - Portland Business Journal." Last modified 2017. Accessed 5 Jun 2018. https://www.bizjournals.com/portland/news/2017/11/20/patients-should-beware-of-stem-cell-quackery.html.