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

About three months earlier the woman had opted for a relatively new kind of cosmetic procedure at a different clinic in Beverly Hills—a face-lift that made use of her own adult stem cells. First, cosmetic surgeons had removed some the woman's abdominal fat with liposuction and isolated the adult stem cells within—a family of cells that can make many copies of themselves in an immature state and can develop into several different kinds of mature tissue. In this case the doctors extracted mesenchymal stem cells—which can turn 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 than $20,000, Wu recollects. Such face-lifts supposedly rejuvenate the skin because stem 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 20 years to reduce the appearance of wrinkles. The principal component of such fillers is calcium hydroxylapatite, a mineral with which cell biologists encourage mesenchymal stem cells to turn into bone—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 turn into bone or other out-of-place tissues once again.

Dozens, perhaps hundreds, of clinics across the country offer a variety of similar, untested stem cell treatments for both cosmetic and medical purposes. Costing between $3,000 and $30,000, the treatments promise to alleviate everything from wrinkles to joint pain to autism. The U.S. Food and Drug Administration (FDA) has not approved any of these treatments and, with a limited budget, is struggling to keep track of all the unapproved therapies on the market. At the same time, pills, oils, creams and moisturizers that allegedly contain the right combination of ingredients to mobilize the body's 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 Cell 100, for example, MEGA STEM and Apple Stem Cell Cloud Cream. 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 buy them and researchers hoping to conduct clinical trials for promising stem cell medicine.

When is a skin cream a drug?
So far, the FDA has only approved one stem cell treatment: a transplant of bone marrow stem cells for people with the blood cancer leukemia. Among the increasing number of unapproved stem 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. District Court 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 as an "unapproved biological drug product." The decision hinged on what constitutes "minimal manipulation" of cells in the lab before they are injected into patients. In the treatment that the FDA won the right to regulate, stem 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 two. Regenerative Sciences now offers the legally problematic treatment at a Cayman Island facility.

Many stem cell cosmetics reside in a legal gray area. Unlike drugs and "biologics" made from living cells and tissues, cosmetics do not require premarket approval 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 letter on its Web site warning Lancôme, a division of L'Oréal, that the way it describes its Genifique skin care products qualify the creams and serums as unapproved drugs: they are supposed to "boost the activity of genes," for example, and "improve the condition of stem cells." Other times the difference between needing or not needing FDA approval comes down to linguistic nuance—the difference between claiming that a product does something or appears to do something.

Personal Cell Sciences, in Eatontown, N.J., sells some of the more sophisticated stem cell–based cosmetics: an eye cream, moisturizer and serum infused with chemicals derived from a consumer's own stem cells. According to its website and marketing materials, these products help "make skin more supple and radiant," "reduce the appearance of fine lines and wrinkles around the eyes and lips," "improve cellular renewal" and "stimulate cell turnover for renewed texture and tone." In exchange for $3,000, Personal Cell Sciences will arrange for a participating physician to vacuum about 60 cubic centimeters (one quarter cup) of a customer's fat from beneath his or her skin and ship it on ice to American CryoStem Corp. in Red Bank, N.J., where laboratory technicians isolate and grow the customer's mesenchymal stem cells to around 30 million strong. Half these cells are frozen for storage; from the other half, technicians harvest hundreds of different kinds of exuded growth factors and cytokines—molecules that help heal damaged cells and encourage cells to divide, among other functions. These molecules are mixed with many other ingredients—including green tea extract, caffeine and vitamins—to create the company's various "U Autologous" skin care products, which are then sold back to the consumer for between $400 and $800. When the customer wants a refill, technicians thaw some of the frozen cells, collect more cytokines and produce new bottles of cream.

In an unpublished safety trial sponsored by Personal Cell Sciences, Frederic Stern of the Stern Center for Aesthetic Surgery in Bellevue, Wash., and his colleagues monitored 19 patients for eight weeks as they used the U Autologous products on the left sides of their faces. A computer program meant to objectively analyze 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. Analysis of tissue biopsies revealed increased levels of the protein elastin, which helps keep skin taut, and no signs of unusual or cancerous cell growth.

Only skin deep?
Supposedly, the primary active ingredients in the U Autologous skin 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 can suppress the immune system or provoke it; they can also change a cell's shape, modulate its metabolism and force it to migrate from one location to another like a cowboy corralling cattle. Researchers have only named and characterized some of the many cytokines that stem cells secrete. Some of these molecules certainly help repair damaged cells and promote cell survival. Others seem to be involved in the development of tumors. In fact, some recent evidence suggests that the cytokines released by mesenchymal stem cells can trigger tumors by accelerating the growth of dormant cancer cells. Personal Cell Sciences does not pick and choose among the cytokines exuded by its customers' stem cells—instead, it dumps them all into its skin care products.

Based on the available evidence so far, topical creams containing cytokines from stem cells pose far less risk of cancer than living stem cells injected beneath the skin. But scientists do not yet know enough about stem cell cytokines to reliably predict everything they will do when rubbed into the skin; they could interact with healthy skin cells in a completely unexpected way, just as the unintended interplay between calcium hydroxylapatite and stem cells produced bones in the Los Angeles woman's eye. Stern acknowledges that unusual tissue growth is a concern for any treatment based on stem cells and the chemicals they release. "Down the line, we want to continue watching that," he says. Unlike 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 Cell Sciences, says the fact that U Autologous skin care products contain such a diversity of cytokines does not bother him: "I've seen worse things out there. I've been putting this formulation for almost a year on myself prior to the study. I'm the best guinea pig here."

Beyond the considerable risks to consumers, unapproved stem cell treatments also threaten the progress of basic research and clinical trials needed to establish safe stem cell therapies for serious illnesses. By harvesting stem cells, subsequently nourishing them in the lab and transplanting them back inside the human body, scientists hope to improve treatment for a variety of medical conditions, including heart failure, neurodegenerative disorders like Parkinson's, and spinal cord injuries—essentially any condition in which the body needs new cells and tissues. Researchers are investigating many stem cell therapies in ongoing, carefully controlled clinical trials. Some of the principal questions entail which of the many kinds of stem cells to use; how to safely deliver stem cells to patients without stimulating tumors or the growth of unwanted tissues; and how to prevent the immune system from attacking stem cells provided by a donor. Securing funding for such research becomes all the more difficult if shortcuts taken by private clinics and cosmetic manufacturers—and the subsequent botched procedures and unanticipated consequences—imprint a stigma on stem cells.

"Many of us are super excited about stem cells, but at same time we have to be really careful," says Paul Knoepfler, a cell biologist at the University of California, Davis, who regularly blogs about the regulation of stem cell treatments. "These aren't your typical drugs. You can stop taking a pill and the chemicals go away. But if you get stem cells, most likely you will have some of those cells or their effects for the rest of your life. And we simply don't know everything they are going to do."

14 Comments

1. 1. lamorpa 08:49 AM 12/17/12

   Seems like a self-correcting situation. Headline: Dangerous Cosmetic Treatments Turn Out to be Dangerous

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2. 2. Johnay 12:43 PM 12/17/12

   People are freaked out about GMO crops, and meanwhile this crap's going on.

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3. 3. greenhome123 06:22 PM 12/17/12

   sounds like it would have worked fine if they didn't inject the dermal filler in addition to the stem cells, which seems to have made the stem cells turn to bone. I do think that companies should be required to have at least a year long safety study on animals before experimenting on humans with these types of cosmetic procedures. But, overall I still think stem cells are the future of medicine.

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4. 4. hankroberts 11:21 PM 12/17/12

   How long til hackers start coming up with new and innovative things for stem cells to turn into? When you can make bone, how long til you can arrange that, make structures as forms, then build other things on those, eh?

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5. 5. StemCellPioneers 04:27 PM 12/18/12

   The patient can sue the doctor for malpractice as this is what it sounds like it is. As usual, this incident will be used by those who refuse to deal in the realities that patients are dying who are being denied access to clinically relevant treatments given by physicians that use their own stem cells. There are thousands of studies on safety. It's time for a serious discussion on having guidelines that physicians can follow and a national registry for patients that they have treated. The FDA's strict regulation is doing no more than causing patients to take risks offshore and from doctors like the one in this article who fail to follow safety guidelines. While this woman was not dying from her condition, there are millions of patients who are. There are too many with conflicts of interests that are standing in the way of meaningful discussions of how to resolve this problem. The only ones without conflicts are the patients themselves who are being denied their civil liberties. I am disappointed that the author chose to only give one side to the story.
   

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6. 6. Zchick1836 05:28 PM 12/18/12

   Interesting article. It does sound like malpractice. The real issue is getting safe AdMSC treatments in our country, not for the purpose of cosmetic procedures, but for devastating chronic illness. I am an adult stem cell patient for MS. It's not a secret that the FDA moves glacially slow. To think that thousands of peoples lives hang in the balance of this being approved soon, is a very scary thought. No wonder I have so many friends who have had to leave our country to be able to sustain any quality of life. As a patient community, we have bonded together, and are seeking our own treatment alternatives. We are left with no other options but to leave the country. The patient community has been scolded enough by "never take a chance, never break a rule" scientists in looking for quality of life sustaining treatments, that our own country, for some unknown reason, will not approve in ANY timely manner. Please be aware that many in the medical community, and many in the scientific community feel the same as the patient. We feel our cells should have never been declared drugs in the first place, and in turn, it's crazy we find ourselves in this debate at present. FDA over reach at it's finest!

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7. 7. adiyenmeera 01:12 AM 12/19/12

   It is painful to learn of the dangers of cosmetic surgery using stem cells and the sufferings of the patients that go through it. It is difficult to know whether these methods are tested for safety, or whether the processes or chemicals involved do not cause harmful side-effects immediately or even years later.
   Thinking deeply about this, it may be worthwhile to consider alternative natural methods for taking care of the signs and symptoms of ageing. Additionally we may be able to delay its premature onset by adopting natural methods early on, to maintain good physical and mental health. This would possibly enable us to age gradually and gracefully without having to go through the risks of some of the cosmetic surgical methods prevalent today.
   

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8. 8. nthmost 06:29 PM 12/19/12

   That is awesome. I'm going to go reread Schismatrix.

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9. 9. bard groupie 07:03 PM 12/20/12

   As a person with both Parkinson's and Rheumatoid Arthritis, it saddens me to read how medical research with stem cells to treat disabling, painful and/or life altering diseases is at risk in this way. Secondly how money that could help research is instead being spent on vanity. What has happened to growing old gracefully is a social problem not medical or even scientific. Their problem is strickly self perception and greed. Walk in my shoes for an hour, well perhaps sit while wearing my shoes.
   
   I realize I probably won't be alive to see any cures however I have faith that they will be at least close for my granddaugters generation. After all there are already many hurdles, politically, financially, and scientifically. I and many others would be seriously heartbroken to see something such as vanity being the root cause of any more delay in a cure or even beneficial help for so many diseases. Vanity doesn't exist when one of these diseases strikes home.

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10. 10. bucketofsquid in reply to Zchick1836 04:16 PM 12/21/12

    Since there is an enormous industry based solely on defrauding desperate patients of their money in exchange for a painful death, it is quite reasonable for the FDA to move cautiously. It would help if the penalties for falsified drug trials included the death penalty for the guilty parties. It would also help if the FDA engaged the regulatory agencies of nations with good medical and lifespan track records to share data.
    
    I'm a little confused as to how anyone would blame the FDA for not allowing professional liars to endanger the health and lives of the citizens the FDA exists to protect. Not that I'm impressed much by the FDA or the EPA. Both are outdated and need to be replaced by an agency with power over anything that is harmful to human life or that threatens ecological collapse of significant ecosystems.

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11. 11. Zchick1836 in reply to bucketofsquid 09:55 PM 12/21/12

    So, what you're saying bucketsofsquid is that I'm going to suffer a painful death because I trusted a stem cell company to treat my MS? WOW! Interesting how the patients are getting SLAMMED in the media for our decision to seek treatment because we are sick and out of options in our country. Then standing up for the belief that our cells should have never been declared drugs waaaaay back in 2006. Listen carefully...AS PATIENTS WE ARE NOT DEFENDING ANY SPECIFIC COMPANY. We are defending our right to seek treatment in our OWN country, with our OWN cells, with a physician of our OWN choosing. Please don't confuse the issue. So what's your dog in this stem cell debate bucketsofsquid? Do you have a university interest? A research grant at stake perhaps? Big Pharma? Medical doc? CEO, CFO, board member or advisor? The reason I ask is to point out that patients are the only ones with no agenda other then to be well again. We want to regain quality of life with our families, friends and loved ones. We want to be able to work, raise children, and grandchildren. We want the things healthy people take for granted. Simple things like walking, reading a book, and gardening. I don't solely blame the FDA anymore than it sounds like you do. There is a whole list of things that leads to an MS patient to seek stem cell. (I won't bore you with the list!) We've been let down by the entire industry, not just the FDA! Please don't bully or scare the patient! We have been through enough with a life changing diagnosis. We are just fighting to live...

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12. 12. tracyt41 in reply to bucketofsquid 12:46 PM 12/22/12

    Very harsh words, "painful death" and "death penalty". I suppose that would apply to the FDA drugs approved that are inducing painful death from side effects as big pharma profits? Not a lot of accountability to the pharma companies who profit billions on drugs that are dangerous. MS drugs like Tysabri cause PML a fatal brain infection just to name a few. I believe you are missing the point. No one is anti FDA, more so wanting to look at current regulations and adjust accordingly. There is a group out there of last hope patients that their disease is inflicting a painful drawn out death. Are we addressing this with current regulations? We should work together bridging that gap and making sure we are helping these patients. Regenerative medicine is a rapidly changing field, are the regulations adjusting at the same rate? Negative banter and casting blame will do nothing! All talk and no action is counterproductive. Real solutions are needed. That will never happen if approached in this manner. I think there is a huge misconception of the chronically ill patient that seeks treatment. To be dismissed as a incompetent fools getting ripped off seeking snake oil treatment is an insult. I believe it all comes down to communication and opening a line of communication that will allow all sides to be heard. Forget the assumptions and learn the facts. Do I condone seeking controversial treatment for vanity purposes, of course not! We are talking about people with no hope or options. A very different scenario. I am confused as to how someone can make such assumptions without talking with a recipient and getting a patients perspective. There are always two sides to every story, it would be nice if they would present both sides. At the end of the day we are talking about people who are dying of a devastating illness. It puts things into a better perspective if you see it as it truly is. Thank you for taking time to read this.

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13. 13. billdtnt 03:09 PM 12/22/12

    A fool and his money are soon parted." This is not a stem cell problem, it's a medical "quack" problem. Quacks have been performing "medical" procedures since the beginning of time. The stem cells performed exactly as they should have performed. It was the dermal filler, used in error by an inexperienced doctor (quack, in my opinion), that caused the problems.
    
    Let the buyer beware! Anyone seeking a medical treatment of any kind (much less an elected "cosmetic" procedure) is responsible to him/herself to perform the research necessary to insure their physician has the skill/expertise to perform the procedure. At the end of the day, it's your body and your choice.
    
    Is there more research to be done with stem cells? Absolutely; and it's being researched/implemented successfully for a multitude of illnesses/procedures around the world. The FDA's current position on stem cells is one of "divide and conquer" vs "inspire and promote."
    
    Stem cell therapy can, will and is having a profound impact on the future of many if not the majority of illnesses.
    

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14. 14. wrcsmith 02:57 AM 12/31/12

    Perhaps with more dermal filler, this application will put Viagra and similars out of business. The clicking might be distracting.

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