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Perspective

Perspective
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Stem cell stratagems in alternative medicine

Stem cell research has attracted an extraordinary amount of attention and expectation due to its potential
for applications in the treatment of numerous medical conditions. These exciting clinical prospects have
generated widespread support from both the public and private sectors, and numerous preclinical studies
and rigorous clinical trials have already been initiated. Recent years, however, have also seen alarming
growth in the number and variety of claims of clinical uses of notional ‘stem cells’ that have not been
adequately tested for safety and/or efficacy. In this article, I will survey the contours of the stem cell
industry as practiced by alternative medicine providers, and highlight points of commonality in their
strategies for marketing.

KEYWORDS: alternative medicine n cosmetics n fresh cells n nutraceuticals n stem cell Douglas Sipp
applications n stem cell tourism RIKEN Center for Developmental
Biology, 2–2-3 Minatojima
Minamimachi, Chuo-ku, Kobe,
Alternative medicine is broadly defined as the stem cells, and in recognition of the wide range 650-0047, Japan
set of healthcare practices that falls outside of of assertions made by many such practices that Tel.: +81 783 063 043
Fax: +81 783 063 990
the mainstream of established medical practice range from therapeutic applications to poorly sipp@cdb.riken.jp
in a given country or culture [101] . An equally defined improvements in wellbeing, appearance
important defining characteristic, however, and and vitality.
one that I will use in this article, is reliance on Alternative medicine, and the related realms
speculation, anecdote and appeals to authority, of complementary, holistic and integrative medi-
rather than evidence from rigorously designed cine, encompass a wide range of approaches
scientific experiments to support claims. to healthcare, including practices adapted
Indeed, in an influential editorial, the editors from Chinese, Indian, Native American, and
of the New England Journal of Medicine based European folk medicine, homeopathy, chiro-
their own definition on evidentiary standards, practic medicine, naturopathy, aromatherapy,
calling alternative medicine the set of health- crystal therapy, herbal supplements, nutrient
care practices that has “not been scientifically megadoses, biofeedback, electric and magnetic
tested and [whose] advocates largely deny the therapies, and faith healing. These approaches
need for such testing” [1] , which was echoed in are distinguished from evidence-based medi-
a statement by the editors of the Journal of the cine in that either their therapeutic claims for a
American Medical Association, which went so wide range of conditions have been tested and
far as to repudiate the distinction: “There is no found to be no more effective than placebo, or
alternative medicine. There is only scientifically they have not been subject to any rigorous stud-
proven, evidence-based medicine supported by ies of safety and efficacy [3,4] . Given the diverse
solid data or unproven medicine, for which sci- nature of the approaches categorized as alterna-
entific evidence is lacking” [2] . For the purposes tive medicine, it has proven difficult to develop
of this article, I define ‘alternative medicine’ reliable figures on usage and market size, but it
as any purportedly therapeutic approach that has been estimated that between 30 and 50%
is not validated by, or which does not seek to of all Americans use at least one alternative or
attain, rigorous scientific evidence for its claims complementary treatment, giving a total market
prior to offering them commercially. The areas size of over US$40 billion [5,6] .
of wellness, cosmetics, esthetics and quality of I will argue that untested and under-regulated
life, which are typically subject to less rigorous uses of ‘stem cells’ represent a new and increas-
testing and regulation than medical products, ingly popular class of alternative medicine prod-
fall into the same spectrum of poor evidentiary ucts. The marketing of these nostrums relies on
support, and have here been classed together claims that such products use, mimic, activate
with alternative medicines to illustrate the diver- or enhance stem cell functions for medicinal,
sity of untested claims surrounding the use of cosmetic, anti-aging or other quality-of-life

10.2217/RME.11.13 © Douglas Sipp Regen. Med. (2011) 6(3), 407–414 ISSN 1746-0751 407
Perspective Sipp

purposes. It is important to note that in the of claims regarding the types of cells used,
great majority of instances, it is impossible to methods of delivery and conditions treated.
determine whether the substances that are being A scan of English-language websites reveals
used in these alternative treatments are com- unsupported claims for therapeutic uses of
posed entirely of, or even contain, bona fide stem bone marrow cells  [104] , umbilical cord blood
cells, and that in a great many cases, such as cells [105] , adipose-derived stem cells [106] , olfac-
alleged applications of injected human embry- tory ensheathing glial cells [107] , fetal stem cells
onic [201] or induced pluripotent stem cells [102] [108,109] , embryonic stem cells [110] and, in at least
(which would be associated with a significant one case, induced pluripotent stem cells [102] .
risk of tumor formation), they clearly do not. Cell solutions may be delivered intravenously,
For this reason, I would like to emphasize that or in  situ into tissues including spinal cord,
in using the term ‘stem cell(s)’ in the present ­peritoneum, myocardium and brain.
article, I am referring to claims made by the The range of therapeutic claims varies by
advertisers of such products, and that the true provider, but these tend to cluster around
identity of the material in question is unverified, neuro­logic, metabolic, cardiovascular and auto­
and should be treated as such. immune disorders. One list maintained by the
Alternative medical uses of the stem cell Repair Stem Cell Institute claims that somatic
concept (meaning those that have not been stem cells of various types are effective in the
subjected to rigorous testing for safety and treatment of more than 180 conditions [111] .
efficacy) can be categorized roughly into one Beike Biotechnology includes more than 80
of four varieties: putative therapeutic uses of diseases and traumas among its “treatable con-
human ‘stem cells’; ‘fresh’ or ‘live’ cell treat- ditions” [105] . EmCell, a “fetal stem cell” clinic
ments using lyophilized animal cells; nutritional in Russia lists around 70 [109] . Geeta Shroff, an
supplements that purport to enhance endo­ Indian obstetrician who uses “embryonic stem
genous stem cell function, or to contain stem cells” at her clinic in Delhi filed a patent claim-
cell extracts; and cosmetic products claiming ing utility in the treatment of nearly 80 specific
either to contain or act on stem cells. Each of conditions, in addition to general efficacy in
these categories in fact represents a diverse col- “cancer, liver and kidney disorders, nervous
lection of products, with heterogeneous, often system disorders, skin disorders, autoimmune
conflicting, theoretical bases and therapeutic disorders, genetic disorders, eye disorders, mus-
aspirations. I will nonetheless seek to provide culoskeletal disorders, fertility and reproductive
an overview of each before highlighting features disorders and cardiovascular disorders” [201] . A
that appear to be common to all. separate Indian clinic boasts of “successfully
treating over 500 diseases” [112] by combining
Human stem cell treatments stem cells with ayurvedic medicine.
Much has already been written about the pheno­ The opacity and volatility of this industry
menon commonly referred to as ‘stem cell tour- makes it is nearly impossible to gauge its true
ism’ in both the mainstream and scientific extent. A noted Chinese bioethicist stated in
media, as well as in the peer-reviewed literature. 2009 that there were between 100 and 150
Studies of the commercial delivery of unproven stem cell clinics in that country alone [15] , while
stem cell-based treatments have focused on the one report on stem cell clinical activities in
claims made by providers [7] , the global scope of Russia asserted that as many as 500 clinics were
the industry [8,9] , legal, regulatory and ethical engaged in the marketing of unproven stem cell
issues [10,11] , and ana­lysis of patient blogs [12] and treatments [16] . English-language websites have
media accounts [13] . Research societies and dis- also proliferated in recent years, and while no
ease-focused advocacy groups have additionally systematic attempt has been made to enumerate
issued warnings to patients regarding untested them, representative samples have appeared in
and unregulated cell-based products [14,103] . mainstream and scientific publications [7,9,17,18] ,
The intensity of this response seems justi- and the International Society for Stem Cell
fied by the growing number of companies now Research is currently developing a database of
engaged in marketing unproven stem cell treat- stem cell treatment providers based on degrees
ments and patients seeking out their services, of compliance with internationally recognized
as well as the breadth of the therapeutic claims standards of practice and ethical conduct [14] .
made by providers and the increasing sophis- Information on revenue is also scarce, but
tication of their marketing efforts. Providers estimations for some clinics can be made on
of ‘stem cell’ treatments make a broad range self-reported fee structures and patient numbers,

408 Regen. Med. (2011) 6(3) future science group


Stem cell stratagems in alternative medicine Perspective
as well as other indirect sources. Regenerative (fresh cell) therapy spas in Switzerland and
Sciences, a small US-based company that Germany, and attracting prominent clien-
marketed injections of cultured autologous tele, including several heads of state [119] . This
stem cell for joint disorders, stated that it was approach, which clearly predates the modern
treating approximately 20 patients per month concept of the stem cell, has remained a fea-
at US$7000–$9000 per treatment [19] , which ture of the alternative medicine landscape in
would amount to an annual revenue of from Germany and Switzerland for decades, and has
$1.7 to $2.1 million. The owner of a second US spread to other parts of the world, including
clinic shut down by federal authorities, Stem Mexico and Southeast Asia [120,121] , as well. In
Cell Pharma, is reported to have earned over general terms, the supposed theoretical basis for
$900,000 by arranging for the treatment of fresh cell treatments appears to be that young
just 34 patients over a 5‑year period prior to his cells from different species have the ability to
arrest [113] . A judgment in favor of one principal rejuvenate aging or damaged tissue.
in the company Stem Cell Biotherapy against a The increased public awareness of stem cells
former partner indicates that the business was val- in the 21st century appears to have given this
ued at least $1,700,000 at the time of its dissolu- unconventional practice a new lease on life, and
tion [114] . And, in its Summer 2010 Information practitioners that previously labeled their prod-
Guide, the Shenzhen-based Beike Biotechnology ucts ‘live’ or ‘fresh’ cells, now use stem cells as a
reports that its cells are used in the treatment of familiar point of reference and marketing tool.
“over 200 patients every month” [115] at an aver- As with companies that sell human ‘stem cell’
age rate (for patients from outside of China) of treatments, there is great diversity in the types of
$26,300 per treatment; Chinese patients pay a cells used and therapeutic claims. MF‑III, a Swiss
fraction of this amount. The X‑Cell Center in franchising operation, advertises sheep placenta
Köln (Germany) states on its website [116] that extracts in capsule form as “Live Cell Therapy
it has treated over 3000 patients, and provides a (Sheep Stem Cell Therapy),” and asserts that its
price list ranging from €5550 to 25,500 ($7000 product will “effectively stimulate the cells of
to $27000), depending on the procedure [117] . the specific organ systems concerned with obes-
There would appear to be little to no inde- ity, arthritis, chronic fatigue, asthma, degenera-
pendent oversight over the formulation of mate- tive brain disease, osteoporosis, circulatory dis-
rials used at many stem cell clinics, making it turbances, sexual dysfunction, male impotence,
impossible to verify whether bona fide stem cells diabetes mellitus, hormonal disturbances, skin
are being used. In several cases, patients have eruptions, and many other metabolic ailments”
not received the treatment advertised. In 2010, [122] . BRCO Stem Cell Indonesia prescribes the
the UK General Medical Council determined use of fetal animal (rabbit) precursor cells for
that a clinic in Rotterdam that had been visited conditions including spinal cord injury, diabe-
by multiple British patients used bovine, not tes, Down syndrome, infertility and aging [121] .
human cells, in its treatments, and sanctioned The company Stem Cell Biomedics [123] , which
the physician in charge [118] . In 2009, ana­lysis advertises “fetal precursor stem cell therapy,”
of a transplant-derived growth that developed lists over 150 medical indications.
in a boy treated at a Moscow clinic with “fetal Some ‘fresh cell’ practitioners have sought
neural stem cells” revealed that the content of the to enter more highly regulated markets as
injection “was little more than a poorly charac- well. Stem Cell Biomedics, in association with
terized heterogeneous slurry of dissociated fetal the Malaysian firm Fetal Cell Technologies
brain” [20] . International, which purports to use prepara-
tions from fetal rabbits and is advised by physi-
Fresh cell therapy cians in Switzerland and Germany [124] , held
The use of conditioned animal cells, tissues and educational programs in Australia in 2010
extracts in the treatment of human health con- advertising treatments for a wide range of condi-
ditions dates back nearly a century, to work in tions, including autism, Down’s syndrome and
the 1920s and 1930s by European physicians aging [125] . As the treatments are delivered in
such as Paul Niehans in Switzerland and Sergei other countries, they fall outside the jurisdic-
Voronoff in France. Niehans, who worked with tion of the Therapeutic Goods Administration,
freeze-dried (lyophilized) cells, mainly from Australia’s competent authority in this area,
sheep, was particularly influential in building providing an example of the evasion of over-
the therapeutic reputation of such treatments, sight enabled by cross-border marketing and
spawning a cottage industry of Frischzellen ­regulatory arbitrage.

future science group www.futuremedicine.com 409


Perspective Sipp

Stem cell-enhancing into circulation in the body where they can be


nutritional supplements used for repairing and replacing dysfunctional
A number of stem cell entrepreneurs have cells” [131] .
developed ingestible products that they claim
activate, mobilize or cause the proliferation of Cosmetic applications
the customer’s own stem cells. Distinct from & esthetic surgery
both human stem cell and animal ‘fresh cell’ In addition to the therapeutic and rejuvenation
treatments, these products are noninvasive, claims made for stem cells and related products,
and do not require the consumer to visit a spe- there is an emerging industry sector that uses the
cific treatment location, making them ideally stem cell label to sell treatments and products
suited to mail-order sales over the internet. for purely esthetic purposes. These can take the
StemEnhance®, a botanical extract purported form of injections of human or animal cells, food
to increase the number of circulating stem supplements, or skin creams and lotions that are
cells, is perhaps the most widely promoted of purported to either include stem cell extracts or
these products. Using a multilevel marketing activate endogenous stem cells transdermally.
approach [126] , StemTech HealthSciences, the Mibelle Biochemistry has developed a line of
US-based company that developed the prod- skincare products that makes use of “an encap-
uct, has succeeded in generating global promo- sulated extract of cultured apple stem cells,”
tion of its products through an international which it claims reduce facial wrinkles and other
network of distributors. The company claims effects of aging [132] . (They also sell a separate
to have sold more than $1  million worth of product based on stem cells from grapes [133] .)
StemEnhance capsules in its first month in BioLogic Solutions advertised the Stem Cell
business [127] , and to be approaching $100 mil- Therapy skin cream, which it claimed “awakens
lion in total sales. (Given the nature of the mar- your skin’s stem cells so they generate many new
keting scheme, however, it is unclear whether skin cells like when you were younger” [134] (The
these products reached end users or remain in BioLogic Solutions company website appears
distributor inventories.) now to be defunct.)
Perhaps encouraged by this apparent mar- In Korea, RNL Bio, a company with aspira-
keting success, others have begun to release tions to develop stem cell therapies for diabetes,
stem cell-activating products. Aidan Products spinal cord injury, ischemic heart disease and
(AZ, USA), established by the founder of the stroke, launched a line of stem cell-based cos-
Institute of Cellular Medicine, has begun to metics branded as Dr Jucre, claiming it to be the
market Stem-Kine, a product combining a pro- “first cosmetics line that contains human adipose
prietary mix of high-dose vitamin D, b‑glucan derived stem cells [as] the active ingredient” [135] .
and ellagic acid, which it claims achieves a last- An investor relations presentation made by the
ing increase in circulating CD133 and CD34 company’s CEO in 2007 referred to the cosmet-
cells [21] . The company suggests on its website ics line, along with its private stem cell banking
that such stem cells have been shown to have and pet cloning businesses as a “cash cow” [136] .
“effects on health, wellness, and regeneration,” The Dr Jucre online shop currently sells 30 ml of
with impacts on such ailments as myocardial eye cream for $119, and a 28‑vial set of “Million
infarction, Alzheimer’s disease and erectile dys- Stem Cell Magic Concentrate” for $1220 [137] .
function [128] . MF‑III, the Swiss maker of sheep Some stem cell treatment providers also
live cell capsules, also offers a line of “vegetal pla- specialize in cosmetic applications. CellPort
centa” products with “stem cell extraction meth- Clinic in Yokohama was the first in Japan to
odology,” which it states are of equal efficacy to offer autologous adipose-derived stem cell injec-
sheep placenta [129] in their rejuvenating effects. tions for breast and buttock augmentation [138] .
The market for stem cell ‘nutraceuticals’ has Numerous other plastic surgery clinics followed
since become more specialized, with the intro- suit, and the practice has spread to neighboring
duction of niche products such as Stemulite, countries as well. In Barbados, the now-defunct
which promises to “improve the immune system Institute of Regenerative Medicine offered injec-
and stimulate your own bone marrow to pro- tions of unethically sourced “fetal stem cells”
duce new adult stem cells that are transfered for tourists seeking cosmetic enhancement and
[sic] throughout your body via the blood stream anti-aging effects [139] .
repairing damaged cells,” [130] and StemPets®, Esthetic surgery is one of the two areas of
which similarly claims to “promote the natu- medicine in which US-based physicians are
ral release of stem cells from the bone marrow actively challenging the regulation of clinical

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Stem cell stratagems in alternative medicine Perspective
uses of autologous cells by the US FDA (the [113,143–145] or local medical associations [146] .
other being orthopedics). A number of clinics The industry does not, however, show immedi-
treat patients domestically using adipose-derived ate signs of receding.
“stem cells” in the enhancement of breast, lower It appears that, in addition to the reputa-
body or facial appearance [140,141] . This appears tion of stem cells as potential medical miracle-
to have escaped regulatory oversight at present, workers, there are a number of other concepts
but a recent joint statement by the American that may account for their present popularity.
Society for Aesthetic Plastic Surgery (ASAPS) First of these is the idea of stem cells as a ‘natu-
and the American Society of Plastic Surgeons ral’ product, distinct from ‘artificial’ drugs and
(ASPS) recommends “that patients considering devices. The phrase ‘natural healing process’,
facial rejuvenation procedures avoid ‘stem cell for example, is used in descriptions of cardiac
face lifts’ or other fad procedures that have not repair by autologous cells [147] , lyophilized cell
been demonstrated to be effective in clinical skincare products [148] , adipose-derived cells
trials” [142] . An analogous situation had arisen for diabetes  [149] and an algae extract stem cell
in the field of orthopedic surgery, but attracted supplement [150] , among others.
the attention of federal regulators who sought In addition to their naturalness, autologous
an injunction against one of the more visible cells have the advantage of being taken from the
treatment providers, Regenerative Sciences, in patient’s own body. This has legitimate advan-
2010  [19] . Given the methodological similari- tages given that the use of autologous cells mini-
ties in obtaining cells for these procedures, the mizes the risk of immune rejection, but it is pow-
results of that case may have bearing on the erful as a marketing concept as well. Not only do
viability of domestic cosmetic surgery clinics autologous cells have connotations of safety, but
offering autologous stem cell injections as well. they raise ownership and identity issues as well.
In the USA, autologous cells that are more than
The selling power of stem cells minimally manipulated or intended for non­
Use of the term ‘stem cells’ has evolved into a homologous, metabolic or systemic uses are regu-
powerful meme in the marketing of human or lated as biologics, but intense efforts have been
animal cell-based tratments, supplements and made by organizations that seek to deregulate
cosmetics, with associations of health, youth and the clinical use of such cells by appealing directly
beauty. Over the past 10 years, a new alterna- to patients with the idea that the government
tive medicine sector has sprung up to meet con- wants to classify their own cells as drugs  [151] .
sumer demand for healthcare, nutritional and The enthusiastic portrayal of the clinical poten-
esthetic ‘stem cell’ products, and it appears that tial of stem cells, as described by Zarzeczny et al.
business is for the most part, good. This may [13] and Scott et al. [22] , has almost certainly con-
be in part due to the acceleration of demand tributed to the popular perception of their thera-
by incautious statements by scientists in the peutic value as well. For all of these reasons, it
field, or uncritically positive descriptions of the appears that stem cells have rapidly given rise to
therapeutic potential of stem cells in the mass a niche in the alternative medicine market space,
media. Indeed, a recent report by Caulfield et al. which has not evidently been the case for other
found that media accounts of patients traveling promising fields of life sciences research, such as
to receive stem cell injections are increasingly gene therapy, RNA interference or monoclonal
positive in recent years [13] . Similarly, Scott et al. antibodies. A more detailed examination of the
found that descriptive terminology in registered distinctions in the public consciousness between
clinical trials of the use of stem cells in heart stem cells and these other advanced biotechnolo-
failure tended to be more likely to foster “thera- gies may be a fruitful area for future study, as has
peutic misconception,” in which an experimen- been suggested previously [152] .
tal procedure of undetermined clinical efficacy The drive to deregulate also seeks to por-
is described in such a way as to suggest that tray restrictions on the immediate use of stem
it is efficacious, than drug trials for the same cell products in clinical applications in terms
­condition [22] . of limitations on patients’ freedom to choose
Efforts have been made to rein in clinics, [111] . Patient autonomy is one of the fundamen-
particularly those engaged in promoting inter- tal principles of medical ethics, and is being
national travel by patients seeking unproven exercised with increasing frequency, as more
stem cell treatments for serious medical con- patients feel empowered by the free availability
ditions  [14] , and a number of clinics have been of information over the Internet. What some
forced to shut down by government authorities stem cell providers have sought to do, however,

future science group www.futuremedicine.com 411


Perspective Sipp

is to depict any restriction on the marketing of of human cells and tissues. China enacted a new
unproven treatments as a curtailment of patient law on advanced medical technologies in 2009,
choice  [111,153] . In its most extreme forms, this and the Thai Medical Council passed binding
is framed as a conspiracy in which the medical guidelines on such applications in the same year.
establishment, the pharmaceuticals industry, Germany has revised its rules on the clinical
research societies and government agencies are use of autologous stem cells, with a deadline for
colluding to keep effective treatments out of the seeking approval for such uses of 30 December,
hands of patients in the interests of protecting 2012. In Costa Rica, the Ministry of Health shut
status quo business models [154] . down a prominent stem cell clinic in 2010, while
While they are undoubtedly persuasive, even in Hungary arrests were made over the illegal
compelling, none of these conceptualizations marketing of fetal stem cell injections.
overcome the bare fact that very few stem cell Should stem cell interventions currently being
treatments have been shown to be both safe and tested for safety and efficacy gain regulatory
effective in well-designed and rigorous trials. approval, this will also presumably affect the
Despite their great promise, the true potential of commercialization of unsubstantiated stem cell
stem cells in medicine remains largely unrealized products. Not only will this provide a solid evi-
at present, with the notable exception of hemato­ dentiary basis on which patients will be able to
poietic stem cells in the treatment of blood and make informed healthcare decisions, it will open
immune disorders. The popularity and profit- up the possibility of having approved treatments
ability of stem cell products in alternative med- reimbursed by insurers. It is uncertain at present
icine speaks more to the power of expectancy which, if any, stem cell-based applications will
and desire than it does to any objective effect in clear these thresholds, but the availability of true
the specific clinical contexts in which they are therapies based on scientific evidence will be a
being delivered. In my opinion it is this power welcome alternative to the baseless offerings of
of persuasion, of manufactured convictions and alternative stem cell medicine at present.
the ‘triumph of hope over experiments’ that
­characterizes alternative medicine as a whole. Financial & competing interests disclosure
The author has no relevant affiliations or financial involve-
Future perspective ment with any organization or entity with a financial
Despite the surging expansion and diversity of interest in or financial conflict with the subject matter or
the commercialization of untested and under- materials discussed in the manuscript. This includes
regulated stem cell interventions in recent years, employment, consultancies, honoraria, stock ownership or
there are signs that this growth may abate in options, expert testimony, grants or patents received or
the near- to mid-term. Competent authorities pending, or royalties.
in numerous countries have begun to develop or No writing assistance was utilized in the production of
enforce regulations over the clinical application this manuscript.

Executive summary
ƒƒ The concept of stem cells has been adopted in an aggressive and widespread manner by providers of unproven medical treatments.
ƒƒ Untested interventions claiming to use human stem cells of various types have emerged into a major international industry.
ƒƒ The use of freeze-dried animal cells is also seeing a resurgence, and frequently adopts terminology from stem cell biology to modernize
the conceptual basis of these products.
ƒƒ A number of nutritional supplement products claiming to enhance stem cell counts or function have been introduced, typically via
web-based marketing approaches.
ƒƒ In addition to medical uses, the use of stem cell products and procedures in cosmetics and esthetic surgery is growing.
ƒƒ Alternative stem cell practitioners appeal to concepts such as naturalness, patient identity and choice, and an us versus them mentality,
in promoting their products and claims.

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