When cosmetic surgeon Allan Wu first heard the woman's complaint, he wondered if she was imagining things or making it upwardly. A resident of Los Angeles in her late sixties, she explained that she could not open up her correct centre without considerable pain and that every time she forced it open, she heard a strange click—a abrupt sound, like a tiny castanet snapping shut. Afterwards examining her in person at The Morrow Institute in Rancho Mirage, Calif., Wu could come across that something was wrong: Her eyelid drooped stubbornly, and the area around her middle was somewhat swollen. Vi and a half hours of surgery later on, he and his colleagues had dug out minor chunks of bone from the woman's eyelid and tissue surrounding her centre, which was scratched but largely intact. The clicks she heard were the bone fragments grinding against ane some other.

About three months earlier the woman had opted for a relatively new kind of cosmetic process at a different clinic in Beverly Hills—a face-lift that made apply of her own adult stalk cells. First, cosmetic surgeons had removed some the woman'south intestinal fat with liposuction and isolated the developed stem cells within—a family of cells that can make many copies of themselves in an immature land and tin develop into several different kinds of mature tissue. In this case the doctors extracted mesenchymal stalk cells—which can plough into bone, cartilage or fat, among other tissues—and injected those cells back into her face, especially around her eyes. The procedure cost her more $20,000, Wu recollects. Such face-lifts supposedly rejuvenate the skin because stalk cells turn into brand-new tissue and release chemicals that help heal aging cells and stimulate nearby cells to proliferate.

During the face-lift her clinicians had also injected some dermal filler, which plastic surgeons have safely used for more than xx years to reduce the advent of wrinkles. The principal component of such fillers is calcium hydroxylapatite, a mineral with which jail cell biologists encourage mesenchymal stem cells to turn into os—a fact that escaped the woman's clinicians. Wu thinks this unanticipated interaction explains her predicament. He successfully removed the pieces of bone from her eyelid in 2009 and says she is doing well today, but some living stem cells may linger in her face. These cells could plough into bone or other out-of-place tissues once once more.

Dozens, mayhap hundreds, of clinics across the state offer a variety of like, untested stalk cell treatments for both corrective and medical purposes. Costing between $3,000 and $30,000, the treatments promise to alleviate everything from wrinkles to joint hurting to autism. The U.S. Food and Drug Administration (FDA) has not approved whatever of these treatments and, with a limited budget, is struggling to keep track of all the unapproved therapies on the market place. At the same time, pills, oils, creams and moisturizers that allegedly contain the correct combination of ingredients to mobilize the torso'due south resident stem cells, or contain chemicals extracted from the stem cells in plants and animals, are popping up in pharmacies and online. There's Stem Jail cell 100, for example, MEGA Stem and Apple Stem Cell Deject Foam. Few of these cosmetics have been properly tested in published experiments, yet the companies that manufacture them say they may heal damaged organs, slow or reverse natural aging, restore youthful energy and revitalize the skin. Whether such cosmetics may also produce unintended and potentially harmful effects remains largely unexamined. The increasing number of untested and unauthorized stem cell treatments threaten both people who purchase them and researchers hoping to conduct clinical trials for promising stalk cell medicine.

When is a peel cream a drug?
So far, the FDA has simply canonical one stem prison cell treatment: a transplant of bone marrow stalk cells for people with the blood cancer leukemia. Amid the increasing number of unapproved stem prison cell treatments, some clearly violate the FDA's regulations whereas others may technically be legal without its approval. In July 2012, for example, the U.S. Commune Courtroom upheld an injunction brought by the FDA against Colorado-based Regenerative Sciences to regulate just one of the company's several stem cell treatments for various joint injuries equally an "unapproved biological drug product." The determination hinged on what constitutes "minimal manipulation" of cells in the lab before they are injected into patients. In the handling that the FDA won the correct to regulate, stalk cells are grown and modified in the lab for several weeks before they are returned to patients; in Regenerative Sciences's other treatments, patients' stem cells are extracted and injected within a day or ii. Regenerative Sciences now offers the legally problematic treatment at a Cayman Island facility.

Many stalk cell cosmetics reside in a legal gray area. Unlike drugs and "biologics" fabricated from living cells and tissues, cosmetics do not crave premarket blessing from the FDA. But stem cell cosmetics often satisfy the FDA's definitions for both cosmetics and drugs. In September 2012 the FDA posted a alphabetic character on its Web site alert Lancôme, a partitioning of L'Oréal, that the manner it describes its Genifique skin care products qualify the creams and serums every bit unapproved drugs: they are supposed to "heave the action of genes," for example, and "improve the condition of stem cells." Other times the departure betwixt needing or non needing FDA approval comes downwardly to linguistic nuance—the deviation betwixt challenge that a product does something or appears to exercise something.

Personal Cell Sciences, in Eatontown, N.J., sells some of the more than sophisticated stalk cell–based cosmetics: an eye cream, moisturizer and serum infused with chemicals derived from a consumer's ain stalk cells. According to its website and marketing materials, these products help "make peel more supple and radiant," "reduce the advent of fine lines and wrinkles effectually the eyes and lips," "improve cellular renewal" and "stimulate cell turnover for renewed texture and tone." In commutation for $3,000, Personal Jail cell Sciences will arrange for a participating physician to vacuum about lx cubic centimeters (one quarter cup) of a customer's fatty from below his or her skin and transport it on water ice to American CryoStem Corp. in Cherry Banking company, N.J., where laboratory technicians isolate and abound the client'due south mesenchymal stem cells to around 30 one thousand thousand potent. Half these cells are frozen for storage; from the other half, technicians harvest hundreds of unlike kinds of exuded growth factors and cytokines—molecules that assistance heal damaged cells and encourage cells to divide, amidst other functions. These molecules are mixed with many other ingredients—including dark-green tea extract, caffeine and vitamins—to create the visitor'due south various "U Autologous" skin intendance products, which are then sold back to the consumer for between $400 and $800. When the client wants a refill, technicians thaw some of the frozen cells, collect more cytokines and produce new bottles of cream.

In an unpublished condom trial sponsored by Personal Cell Sciences, Frederic Stern of the Stern Middle for Aesthetic Surgery in Bellevue, Wash., and his colleagues monitored xix patients for eight weeks as they used the U Autologous products on the left sides of their faces. A reckoner program meant to objectively clarify photos of the volunteers' faces measured an average of 25.6 percent reduction in the volume of wrinkles on the treated side of the face. Assay of tissue biopsies revealed increased levels of the protein elastin, which helps continue skin taut, and no signs of unusual or cancerous prison cell growth.

Only skin deep?
Supposedly, the chief active ingredients in the U Autologous peel care products are the hundreds of different kinds of cytokines they contain. Cytokines are a large and diverse family of proteins that cells release to communicate with and influence one another. Cytokines can stimulate cell division or halt it; they tin can suppress the immune system or provoke it; they can also alter a cell'south shape, modulate its metabolism and strength it to migrate from one location to another similar a cowboy corralling cattle. Researchers take merely named and characterized some of the many cytokines that stalk cells secrete. Some of these molecules certainly assistance repair damaged cells and promote cell survival. Others seem to be involved in the evolution of tumors. In fact, some contempo evidence suggests that the cytokines released by mesenchymal stem cells tin can trigger tumors past accelerating the growth of dormant cancer cells. Personal Cell Sciences does not pick and choose among the cytokines exuded past its customers' stalk cells—instead, it dumps them all into its skin care products.

Based on the bachelor evidence so far, topical creams containing cytokines from stem cells pose far less chance of cancer than living stalk cells injected beneath the peel. Only scientists exercise not withal know enough about stem cell cytokines to reliably predict everything they volition do when rubbed into the skin; they could interact with healthy pare cells in a completely unexpected way, just every bit the unintended interplay betwixt calcium hydroxylapatite and stem cells produced basic in the Los Angeles woman'due south eye. Stern acknowledges that unusual tissue growth is a business for any treatment based on stem cells and the chemicals they release. "Down the line, we want to go along watching that," he says. Dissimilar many other clinics, he and his colleagues have been keeping tabs on their patients through regular follow-ups. John Arnone, CEO of American CryoStem and founder of Personal Prison cell Sciences, says the fact that U Autologous pare care products comprise such a diverseness of cytokines does not carp him: "I've seen worse things out there. I've been putting this conception for about a yr on myself prior to the report. I'thou the best guinea hog here."

Beyond the considerable risks to consumers, unapproved stem cell treatments also threaten the progress of basic enquiry and clinical trials needed to found condom stem jail cell therapies for serious illnesses. By harvesting stem cells, later on nourishing them in the lab and transplanting them dorsum within the human being body, scientists promise to improve treatment for a variety of medical weather, including heart failure, neurodegenerative disorders like Parkinson'southward, and spinal string injuries—substantially whatsoever condition in which the body needs new cells and tissues. Researchers are investigating many stem prison cell therapies in ongoing, advisedly controlled clinical trials. Some of the principal questions entail which of the many kinds of stem cells to use; how to safely deliver stalk cells to patients without stimulating tumors or the growth of unwanted tissues; and how to prevent the allowed system from attacking stem cells provided by a donor. Securing funding for such research becomes all the more than difficult if shortcuts taken past private clinics and corrective manufacturers—and the subsequent botched procedures and unanticipated consequences—imprint a stigma on stalk cells.

"Many of united states of america are super excited well-nigh stem cells, merely at same time we have to be actually careful," says Paul Knoepfler, a cell biologist at the University of California, Davis, who regularly blogs nearly the regulation of stalk cell treatments. "These aren't your typical drugs. You can stop taking a pill and the chemicals get away. Merely if y'all become stem cells, most likely you will have some of those cells or their effects for the rest of your life. And nosotros simply don't know everything they are going to do."