The beauty market abounds with high-end creams and serums that claim the use of stem cells to rejuvenate aging skin.
Selling on the internet and at department stores like Nordstrom, these products promise "breakthrough" applications to plump, smooth, and "reverse visible signs of aging," and at least one product offers to create a "regenerative firming serum, moisturizer, and eye cream" from customers' own stem cells – for a whopping $1200.
The beauty industry is heavily hyping glimmers of the nascent field of stem cell therapy.
Steeped in clinical-sounding terms like "proteins and peptides from pluripotent stem cells," the marketing of these products evokes a dramatic restoration of youthfulness based on cutting-edge science. But the beauty industry is heavily hyping glimmers of the nascent field of stem cell therapy. So what is real and what's not? And is there in fact a way to harness the potential of stem cells in the service of beauty?
Plant vs. Human Stem Cells
Stem cells do indeed have tremendous promise for treating a wide range of diseases and conditions. The cells come from early-stage embryos or, more commonly, from umbilical cord blood or our own bodies. Embryonic stem cells are considered the body's "master" cells because they can develop into any of our several hundred cell types. Adult stem cells, on the other hand, reside in mature tissues and organs like the brain, bone marrow, and skin, and their versatility is more limited. As an internal repair system for many tissue types, they replenish sick, injured, and worn-out cells.
Nowadays, with some sophisticated chemical coaxing, adult stem cells can be returned to an embryonic-like blank state, with the ability to become any cell type that the body might need.
Beauty product manufacturers convey in their advertising that the rejuvenating power of these cells could hold the key to the fountain of youth. But there's something the manufacturers don't always tell you: their products do not typically use human stem cells.
"The whole concept of stem cells is intriguing to the public," says Tamara Griffiths, a consultant dermatologist for the British Skin Foundation. "But what these products contain is plant stem cells and, more commonly, chemicals that have been derived from plant stem cells."
The plant stem cells are cultured in the lab with special media to get them to produce signaling proteins and peptides, like cytokines and chemokines. These have been shown to be good for reducing inflammation and promoting healthy cell functioning, even if derived from plants. However, according to Griffiths, there are so many active ingredients in these products that it's hard to say just what role each one of them plays. We do know that their ability to replenish human stem cells is extremely limited, and the effects of plant stem cells on human cells are unproven.
"...any cosmetic that is advertised to be anti-aging due to plant stem cells at this time is about as effective as all the skin creams without stem cells."
Whether products containing plant cell-derived ingredients work better than conventional skin products is unknown because these products are not regulated by the U.S. Food and Drug Administration and may rest on dubious, even more or less nonexistent, research. Cosmetics companies have conducted most of the research and the exact formulas they devise are considered proprietary information. They have no incentive to publish their research findings, and they don't have to meet standards imposed by the FDA unless they start using human cells in their products.
"There are biological limits to what you can do with plant cells in the first place," says Griffiths. "No plant stem cell is going to morph into a human skin cell no matter what magic medium you immerse it in. Nor is a plant cell likely to stimulate the production of human stem cells if applied to the skin."
According to Sarah Baucus, a cell biologist, for any type of stem cell to be of any use whatsoever, the cells must be alive. The processing needed to incorporate living cells into any type of cream or serum would inevitably kill them, rendering them useless. The splashy marketing of these products suggests that results may be drastic, but none of these creams is likely to produce the kind of rejuvenating effect that would be on par with a facelift or several other surgical or dermatological procedures.
"Plant stem cell therapy needs to move in the right direction to implement its inherent potential in skin care," researchers wrote in a 2017 paper in the journal Future Science OA. "This might happen in the next 20 years but any cosmetic that is advertised to be anti-aging due to plant stem cells at this time is about as effective as all the skin creams without stem cells."
From Beauty Counter to Doctor's Clinic
Where do you turn if you still want to harness the power of stem cells to reinvigorate the skin? Is there a legitimate treatment using human cells? The answer is possibly, but for that you have to switch from the Nordstrom cosmetics counter to a clinic with a lab, where plastic surgeons work with specialists who culture and manipulate living cells.
Plastic surgeons are experts in wound healing, a process in which stem cells play a prominent role. Doctors have long used the technique of taking fat from the body and injecting it into hollowed-out or depressed areas of the face to fill in injuries, correct wrinkles, and improve the face's curvature. Lipotransfer, or the harvesting of body fat and injecting it into the face, has been around for many years in traditional plastic surgery clinics. In recent years, some plastic surgeons have started to cull stem cells from fat. One procedure that does just that is called cell-assisted lipotransfer, or CAL.
In CAL, adipose tissue, or fat, is harvested by liposuction, usually from the lower abdomen. Fat contains stem cells that can differentiate into several cell types, including skin, muscle, cartilage, and bone. Fat tissue has an especially stem cell-rich layer. These cells are then mixed with some regular fat, making in effect a very stem cell-rich fat solution, right in the doctor's office. The process of manipulating the fat cells takes about 90 to 110 minutes, and then the solution is ready to be injected into the skin, to fill in the lips, the cheeks, and the nasolabial folds, or the deep folds around the nose and mouth.
Unlike regular fat, which is often injected into the face, some experts claim that the cell-enriched fat has better, longer-lasting results. The tissue graft grows its own blood vessels, an advantage that may lead to a more long-lasting graft – though the research is mixed, with some studies showing they do and other studies showing the complete opposite.
For almost all stem cell products on the market today in the U.S., it is not yet known whether they are safe or effective, despite how they are marketed.
One of the pioneers in CAL, a plastic surgeon in Brazil named Dr. Aris Sterodimas, says that the stem cells secrete growth factors that rejuvenate the skin -- like the plant stem cells that are used in topical creams and serums. Except that these cells are human stem cells and hence have inherently more potential in the human body.
Note that CAL doesn't actually result in large numbers of fresh, new replacement cells, as might be imagined. It's simply fat tissue treated to make it richer in stem cells, to have more of the growth-inducing proteins and peptides delivered to the dermis layer of the skin.
Sterodimas works alongside a tissue engineer to provide CAL in his clinic. He uses it as a way to rebuild soft tissues in people disfigured by accidents or diseases, or who are suffering the after-effects of radiation treatments for cancer.
Plastic surgeons get plenty of these patients. But how widespread is CAL for beauty purposes? Sterodimas says that he regularly performs the procedure for Brazilians, and it's widely available in Europe and Japan. In the U.S., the procedure hasn't taken off because there is no FDA approval for the various methods used by different doctors and clinics. A few major academic centers in the U.S. offer the treatment on a clinical trials basis and there are several trials ongoing.
But there is a downside to all lipotransfers: the transplanted fat will eventually be absorbed by the body. Even the cell-enriched fat has a limited lifespan before reabsorption. That means if you like the cosmetic results of CAL, you'll have to repeat the treatment about every two years to maintain the plumping, firming, and smoothing effects on the skin. The results of CAL are "superior to the results of laser treatments and other plastic surgery interventions, though the effect is not as dramatic as a facelift," says Sterodimas.
For almost all stem cell products on the market today in the U.S., it is not yet known whether they are safe or effective, despite how they are marketed. There are around 700 clinics in the U.S. offering stem cell treatments and up to 20,000 people have received these therapies. However, the only FDA-approved stem cell treatments use cells from bone marrow or cord blood to treat cancers of the blood and bone marrow. Safety concerns have prompted the FDA to announce increased oversight of stem cell clinics.
As for CAL, most of the clinical trials so far have been focused on using it for breast reconstruction after mastectomy, and results are mixed. Experts warn that the procedure has yet to be proven safe as well as effective. It's important to remember that this newborn science is in the early stages of research.
One question that has also not been definitively settled is whether the transplanted stem cells may give rise to tumors — a risk that is ever-present any time stem cells are used. More research is required to assess the long-term safety and effectiveness of these treatments.
Given the lack of uniform industry standards, one can easily end up at a clinic that overpromises what it can deliver.
In the journal Plastic Reconstruction Surgery in 2014, Adrian McArdle and a team of Stanford University plastic surgeons examined the common claims of CAL's "stem cell facelifts" being offered by clinics across the world. McArdle and his team write: "…the marketplace is characterized by direct-to-consumer corporate medicine strategies that are characterized by unsubstantiated, and sometimes fraudulent claims, that put our patients at risk." Given the lack of uniform industry standards, one can easily end up at a clinic that overpromises what it can deliver.
But according to McArdle, further research on CAL, including clinical trials, is proceeding apace. It's possible that as more research on the potential of stem cells accrues, many of the technical hurdles will be crossed.
If you decide to try CAL in a research or clinical setting, be forewarned. You will be taking part in a young science, with many unknown questions. However, the next time someone offers to sell you stem cells in a jar, you'll know what you're paying for.
Amber Freed felt she was the happiest mother on earth when she gave birth to twins in March 2017. But that euphoric feeling began to fade over the next few months, as she realized her son wasn't making the same developmental milestones as his sister. "I had a perfect benchmark because they were twins, and I saw that Maxwell was floppy—he didn't have muscle tone and couldn't hold his neck up," she recalls. At first doctors placated her with statements that boys sometimes develop slower than girls, but the difference was just too drastic. At 10 month old, Maxwell had never reached to grab a toy. In fact, he had never even used his hands.
Thinking that perhaps Maxwell couldn't see well, Freed took him to an ophthalmologist who was the first to confirm her worst fears. He didn't find Maxwell to have vision problems, but he thought there was something wrong with the boy's brain. He had seen similar cases before and they always turned out to be rare disorders, and always fatal. "Start preparing yourself for your child not to live," he had said.
Getting the diagnosis took months of painful, invasive procedures, as well as fighting with the health insurance to get the genetic testing approved. Finally, in June 2018, doctors at the Children's Hospital Colorado gave the Freeds their son's diagnosis—a genetic mutation so rare it didn't even have a name, just a bunch of letters jammed together into a word SLC6A1—same as the name of the mutated gene. The mutation, with only 40 cases known worldwide at the time, caused developmental disabilities, movement and speech disorders, and a debilitating form of epilepsy.
The doctors didn't know much about the disorder, but they said that Maxwell would also regress in his development when he turned three or four. They couldn't tell how long he would live. "Hopefully you would become an expert and educate us about it," they said, as they gave Freed a five-page paper on the SLC6A1 and told her to start calling scientists if she wanted to help her son in any way. When she Googled the name, nothing came up. She felt horrified. "Our disease was too rare to care."
Freed's husband, a 6'2'' college football player broke down in sobs and she realized that if anything could be done to help Maxwell, she'd have be the one to do it. "I understood that I had to fight like a mother," she says. "And a determined mother can do a lot of things."
The Freed family.
Courtesy Amber Freed
She quit her job as an equity analyst the day of the diagnosis and became a full-time SLC6A1 citizen scientist looking for researchers studying mutations of this gene. In the wee hours of the morning, she called scientists in Europe. As the day progressed, she called researchers on the East Coast, followed by the West in the afternoon. In the evening, she switched to Asia and Australia. She asked them the same question. "Can you help explain my gene and how do we fix it?"
Scientists need money to do research, so Freed launched Milestones for Maxwell fundraising campaign, and a SLC6A1 Connect patient advocacy nonprofit, dedicated to improving the lives of children and families battling this rare condition. And then it became clear that the mutation wasn't as rare as it seemed. As other parents began to discover her nonprofit, the number of known cases rose from 40 to 100, and later to 400, Freed says. "The disease is only rare until it messes with the wrong mother."
It took one mother to find another to start looking into what's happening inside Maxwell's brain. Freed came across Jeanne Paz, a Gladstone Institutes researcher who studies epilepsy with particular interest in absence or silent seizures—those that don't manifest by convulsions, but rather make patients absently stare into space—and that's one type of seizures Maxwell has. "It's like a brief period of silence in the brain during which the person doesn't pay attention to what's happening, and as soon as they come out of the seizure they are back to life," Paz explains. "It's like a pause button on consciousness." She was working to understand the underlying biology.
To understand how seizures begin, spread and stop, Paz uses optogenetics in mice. From words "genetic" and "optikós," which means visible in Greek, the optogenetics technique involves two steps. First, scientists introduce a light-sensitive gene into a specific brain cell type—for example into excitatory neurons that release glutamate, a neurotransmitter, which activates other cells in the brain. Then they implant a very thin optical fiber into the brain area where they forged these light-sensitive neurons. As they shine the light through the optical fiber, researchers can make excitatory neurons to release glutamate—or instead tell them to stop being active and "shut up". The ability to control what these neurons of interest do, quite literally sheds light onto where seizures start, how they propagate and what cells are involved in stopping them.
"Let's say a seizure started and we shine the light that reduces the activity of specific neurons," Paz explains. "If that stops the seizure, we know that activating those cells was necessary to maintain the seizure." Likewise, shutting down their activity will make the seizure stop.
Freed reached out to Paz in 2019 and the two women had an instant connection. They were both passionate about brain and seizures research, even if for different reasons. Freed asked Paz if she would study her son's seizures and Paz agreed.
To do that, Paz needed mice that carried the SLC6A1 mutation, so Freed found a company in China that created them to specs. The company replaced a mouse SLC6A1 gene with a human mutated one and shipped them over to Paz's lab. "We call them Maxwell mice," Paz says, "and we are now implanting electrodes into them to see which brain regions generate seizures." That would help them understand what goes wrong and what brain cells are malfunctioning in the SLC6A1 mice—and help scientists better understand what might cause seizures in children.
Bred to carry SLC6A1 mutation, these "Maxwell mice" will help better understand this debilitating genetic disease. (These mice are from Vanderbilt University, where researchers are also studying SLC6A1.)
Courtesy Amber Freed
This information—along with other research Amber is funding in other institutions—will inform the development of a novel genetic treatment, in which scientists would deploy a harmless virus to deliver a healthy, working copy of the SLC6A1 gene into the mice brains. They would likely deliver the therapeutic via a spinal tap infusion, and if it works and doesn't produce side effects in mice, the human trials will follow.
In the meantime, Freed is raising money to fund other research of various stop-gap measures. On April 22, 2021, she updated her Milestone for Maxwell page with a post that her nonprofit is funding yet another effort. It is a trial at Weill Cornell Medicine in New York City, in which doctors will use an already FDA-approved drug, which was recently repurposed for the SLC6A1 condition to treat epilepsy in these children. "It will buy us time," Freed says—while the gene therapy effort progresses.
Freed is determined to beat SLC6A1 before it beats down her family. She hopes to put an end to this disease—and similar genetic diseases—once and for all. Her goal is not only to have scientists create a remedy, but also to add the mutation to a newborn screening panel. That way, children born with this condition in the future would receive gene therapy before they even leave the hospital.
"I don't want there to be another Maxwell Freed," she says, "and that's why I am fighting like a mother." The gene therapy trial still might be a few years away, but the Weill Cornell one aims to launch very soon—possibly around Mother's Day. This is yet another milestone for Maxwell, another baby step forward—and the best gift a mother can get.
This virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the COVID-19 vaccines for children and teens. A public Q&A will follow the expert discussion.
Thursday, May 13th, 2021
12:30 p.m. - 1:45 p.m. EDT
Virtual on Zoom
You can submit a question for the speakers upon registering.
Dr. H. Dele Davies, M.D., MHCM
Senior Vice Chancellor for Academic Affairs and Dean for Graduate Studies at the University of Nebraska Medical (UNMC). He is an internationally recognized expert in pediatric infectious diseases and a leader in community health.
Dr. Emily Oster, Ph.D.
Professor of Economics at Brown University. She is a best-selling author and parenting guru who has pioneered a method of assessing school safety.
Dr. Tina Q. Tan, M.D.
Professor of Pediatrics at the Feinberg School of Medicine, Northwestern University. She has been involved in several vaccine survey studies that examine the awareness, acceptance, barriers and utilization of recommended preventative vaccines.
Dr. Inci Yildirim, M.D., Ph.D., M.Sc.
Associate Professor of Pediatrics (Infectious Disease); Medical Director, Transplant Infectious Diseases at Yale School of Medicine; Associate Professor of Global Health, Yale Institute for Global Health. She is an investigator for the multi-institutional COVID-19 Prevention Network's (CoVPN) Moderna mRNA-1273 clinical trial for children 6 months to 12 years of age.
About the Event Series
This event is the second of a four-part series co-hosted by Leaps.org, the Aspen Institute Science & Society Program, and the Sabin–Aspen Vaccine Science & Policy Group, with generous support from the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute.