It's not immediately clear what connects the sobering images of cancer survivors on Jeremy Mao's computer screen in Manhattan's Upper West Side with the breathlessly hyped skin creams sold by the city's Midtown retail giants.

But as researchers like Mao expand the potential for stem-cell-aided reconstruction for patients missing a breast or sizeable chunk of lower lip, the cosmetic promise of perkier breasts and fuller lips is following fast behind. So too are the skin-care companies determined to make a little dab of stem cell science go a long way toward plumping up sales in stores such as Macy's, Bloomingdale's and Neiman Marcus.

Credit: Jessica Kolman

Mao, director of the Tissue Engineering and Regenerative Medicine Laboratory at Columbia University College of Dental Medicine in New York, doesn't care much for beauty aids; he wants to figure out how to use stem cells for soft-tissue reconstruction that dramatically improves on existing methods of plastic surgery: transferred fat is problematic because it shrinks, silicon implants because they leak. For Mao's strategy to succeed, implants seeded with stem cells must attract new blood vessels and maintain their designated shape in the long term.

In a proof-of-principle study, Mao's group implanted hydrogel plugs patterned after Eppendorf tube caps into immunodeficient mice. For a subset of the plugs, the researchers added microchannels seeded with adipogenic stem cells derived from human mesenchymal stem cells, and also added basic fibroblast growth factor1. Blood vessels grew into the channels to support new adipose tissue formed within the plug's boundaries. That vascularization, Mao says, offers both a nutrient source for the stem cells and an anchor to which host tissue can attach. The next step on the path toward US Food and Drug Administration (FDA) approval is demonstrating the same success in a sheep or goat model.

The encouraging science behind stem-cell-aided tissue regeneration has led the US Department of Defense to commit $85 million in funding to the new Armed Forces Institute of Regenerative Medicine (AFIRM). (See Stem cells drafted for war on wounds.)

Peter Rubin, co-director of the Adipose Stem Cell Center at the University of Pittsburgh Medical Center in Pennsylvania and a member of an AFIRM-funded consortium, says researchers are pursuing two main strategies. One is to seed adipose-derived stem cells onto carriers such as microbeads or biodegradable hydrogels, introduce them into a tissue bed and allow them to differentiate — the general approach also adopted by Mao. The second is to introduce multiple growth factors to recruit a patient's own adipose stem cells for wound healing.

Could either strategy create more youthful-looking skin? "I think there is absolutely potential to do that," Rubin says. However, the cosmetic skin-care products on offer can't use such invasive strategies. Instead, companies have seized on the regenerative potential of stem cells to promote topically applied cosmetic solutions whose effectiveness is highly debatable.

Skin deep

Creams, serums, emulsions and lotions with names such as Plazan, Amatokin, Peau Magnifique, TSN Recovery and HydroPeptide Serum are all angling for well-off shoppers with a strong aversion to crow's feet or laugh lines. One "resets your skin's 'aging clock' by a minimum of five years". Another offers "improved overall skin appearance by 350%". Most are produced in the United States; none of the claims has been evaluated by the FDA.

Despite celebrity endorsements in glossy magazines, most researchers remain unimpressed. "I have yet to see any solid scientific evidence," says Mao. Rubin is likewise sceptical. "There is a paucity of real data on topical creams that claim to impact stem cells," he says.

There is a paucity of real data on topical creams that claim to impact stem cells. Peter Rubin, University of Pittsburgh Medical Center

The topical products contain stem-cell-stimulating peptides and enzymes ranging from epidermal growth factor to telomerase as active ingredients, but unless those ingredients can get past the epidermal layer, says Rubin, "nothing worthwhile is going to come from it". In a relatively unregulated industry susceptible to marketing ploys, there's little assurance that the current crop of wrinkle-banishing potions contains anything remotely useful, he says. "It could be stem cells, or bacon grease."

Sam Most, a facial reconstructive surgeon at Stanford School of Medicine in California, says stem-cell-related cosmetic marketing is following the time-tested tactic of climbing aboard the bandwagon of hot topics, from collagen to FDA-approved Botox injections. Most says he hasn't specifically analysed the claims of stem-cell-related creams, but his own laboratory experience suggests another major issue: growth factors and enzymes are notoriously temperature-sensitive. "They don't just sit there on the shelf and last," he says.

To do any good, the ingredients would have to remain stable for weeks or months at room temperature, get past the epidermal layer, go into the right cells, and exert the proper stimulation once reaching their destination. And if marketers demonstrated they could do all that, Most thinks, the creams would probably require FDA approval.

Not surprisingly, some companies have finessed their message to avoid such scrutiny. Steve Peck, president of Issaquah, Washington-based Azure Cosmeceuticals, says his company's HydroPeptide Serum ($119 per 30 ml) "forms a film over the skin that feeds the skin the active ingredients over time, similar to a time-release capsule that you would ingest". Liposomes and nanotechnology help to deliver the stem cell factors and plant- and animal-derived peptides deeper into the skin, he says. So does the use of short-chain amino acids — many bound with fatty acids — and the inclusion of the phospholipid lecithin, according to a chemist working with the company.

Peck cautions that FDA regulations don't allow him to claim that the serum works directly in the living dermis layer, although he says the ingredients work indirectly to firm and plump skin cells. The company has commissioned user-group studies, but has yet to publish any data in a peer-reviewed journal.

Going for fat

Even more pricey than the new cosmetics are stem-cell-based skin rejuvenation procedures being offered by a few private clinics. Last year, New Jersey-based plastic surgeon Vincent Giampapa began publicizing his $5,000 "stem cell facelift" – a strategy meant to overcome the natural barrier posed by the epidermis. According to a press release, the "revolutionary technique" involves transplanting stem cells and fat from a patient's lower abdominal area to the subcutaneous fatty layers of her face, "and awakening them as well as the local stem cells within the face with specific stem cell growth factors". Exactly which factors aren't specified, and Giampapa, whose clinic has performed the procedure for four years, didn't respond to repeated inquiries.

Karl-Georg Heinrich, a cosmetic surgeon based in Vienna, Austria, with offices in Moscow and Dubai, has similarly begun extracting adipose-tissue-derived stem cells from his patients in Vienna and reinserting the cells, either mixed with fat or by themselves, for reconstructions elsewhere in the body or face. Heinrich sees the procedure as little more than a liposuction combined with a fat transfer, both of which are already offered at university hospitals. As such, he sees no regulation issues "as long as you use sensible means to process the fat". Yet he concedes a lack of data regarding the cells' post-injection longevity.

Instead of skin creams, Heinrich favours mesotherapy — a series of injections into the patient's subcutaneous fat layer. The technique offered in his clinic is similar to that used for intramuscular Botox injections, but instead uses either stem-cell-related growth factors or a patient's own harvested stem cells to achieve a rejuvenating effect on local adipose tissue.

Of the roughly 60 peer-reviewed articles on mesotherapy published within the past two decades, more than half focus on complications and unwanted side-effects, including delirium with psychotic features, facial cutaneous ulcers, and multifocal scalp abscess with subcutaneous fat necrosis. No study has yet focused on stem-cell-based mesotherapy, although doctors in Thailand are sounding the alarm about a potentially deadly treatment on offer that allegedly removes facial wrinkles with injected animal stem cells. Several doses, a doctor told Bangkok's The Nation, could lead to fatal anaphylactic shock.

Beyond the safety concerns, merely injecting enzymes, peptides or a few thousand stem cells into subcutaneous tissue does not ensure that they are likely to work as intended, says Stanford's Most. "It's like if you find the best wrench ever and throw it onto the car seat. Is your engine going to run better?"

Name your price

For both topical and injected treatments, Most says he knows of no clinical studies demonstrating rejuvenation at the microscopic level, which would be apparent through features such as a thicker epidermal layer and collagen arranged in more parallel bundles. This void hasn't stopped a host of miracle claims. Amatokin, available at high-end department stores such as Macy's and Bloomingdales in New York and Harvey Nichols in London, sells for $190 per 30 ml and comes with a bizarre back-story involving a "super secret" Russian lab whose research on burn victims apparently required razor wire and machine-gun-toting guards. Despite in-house hype that this 'underground' celebrity wrinkle cream represents "the most profound skincare advancement in more than three decades", its alleged success at stimulating expression of stem cell markers in the skin so far lacks peer-reviewed evidence.

Basic Research, Amatokin's parent company in Salt Lake City, Utah, did not respond to enquiries. The United Kingdom's Advertising Standards Authority, however, concluded in July 2008 that claims implying a physiological effect were not supported by product-specific evidence and could mislead consumers. On the basis of its findings, the advertising authority asked Basic Research-owned Voss Laboratories to remove the challenged claims from its Amatokin advertising in the UK.

A direct competitor, RéVive Skincare's Peau Magnifique, retails for $1,500 (for four 1-ml ampoules) at Neiman Marcus and at online retailers. RéVive, of Louisville, Kentucky, has collected the covers of more than 40 glossy magazines to publicize its serum. Beyond the serum's telomerase ingredient that supposedly "converts resting adult stem cells to newly-minted skin cells", the serum contains fibroblast growth factor to stimulate collagen synthesis and "Nobel Prize winning" epidermal growth factor to promote cell turnover.

The identification of epidermal growth factor — along with nerve growth factor — did win its co-discoverers the Nobel Prize in Physiology or Medicine in 1986. And RéVive president and founder Gregory Bays Brown published a cluster of studies in the 1980s and early 90s supporting the benefits of bioengineered epidermal growth factor in treating chronic wounds and second-degree burns. Whether those benefits extend to resetting the wearer's 'aging clock' is less clear.

Insoo Hyun of Case Western Reserve University and co-chair of the Task Force on the Clinical Translation of Stem Cells established by the International Society for Stem Cell Research (ISSCR), says his task force's newly released guidelines focus primarily on disease applications. Nevertheless, he says, many of the same concerns and questions apply to cosmeceuticals, such as whether the claims have been adequately peer reviewed.

A company's reluctance to publish its results because of fears that its secrets will be stolen is neither a new nor a valid argument, Hyun says. The independent review process already incorporates confidentiality agreements designed to protect intellectual property, he says. "You can't hide behind that."

The success and proliferation of these products suggests, however, that the market for beauty will provide ample cover for the foreseeable future.

Related articles:

Stem-cell banking: lifeline or sub-prime?

Stem cell researchers face down stem cell tourism

Offshore stem cell treatments require sensitive regulation

Stick to the guidelines and fewer get hurt