Category: stem cells

In the Flesh: The Embedded Dangers of Untested Stem Cell Cosmetics

On By A.P.In Allan Wu, American CryoStem, Beverly Hills, calcium hydroxylapatite, California, cytokines, Dr. Nakamura, elastin, FDA, Food and Drug Administration, Frederic Stern, Genifique, John Arnone, L'Oréal, Medicine, New Jersey, Paul Knoepfler, Personal Cell Sciences, plastic surgery, Rancho Mirage, Science, Scientific American, stem cells, Stern Center for Aesthetic Surgery, The Morrow Institute, U Autologous, UC Davis, University of CaliforniaLeave a comment

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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.

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.

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.”

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https://www.scientificamerican.com/article.cfm?id=stem-cell-cosmetics&WT.mc_id=SA_emailfriend

Thanks to Dr. Nakamura for bringing this to the attention of the It’s Interesting community.

Chinese scientists turn human urine into brain cells

On By A.P.In Alzheimer's disease, China, kidney, Nature, Neuropsychiatric Disease, Parkinson's disease, pluripotent cells, Science, stem cells, The Brain, Urine1 Comment

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Chinese researchers have developed a new technique for isolating kidney cells from urine and turning them into neural progenitors — –immature brain cells that can develop into various types of glial cells and neurons. Reprogramming cells has been done before, of course, but not with cells gleaned from urine and not via a method this direct. The technique could prove extremely helpful to those pursuing treatments for neurodegenerative disorders like Parkinson’s and Alzheimer’s.

The innovation here is in the source and the method. We know that embryonic stem cells offer potential treatments for neurodegenerative disorders. And we know that we can turn adult human cells–that is, non-embryonic cells gathered from adult humans–into pluripotent cells (those that can become a different type of cell) by reprogramming them, usually with genetically engineered viruses that tamper with the cells’ genetic codes.

But embryonic stem cell treatments are fraught with ethical issues and non-embryonic methods are complicated–and complexity introduces a greater chance of something going wrong (in this case that means mutations and genetic defects). The new method, which taps skin-like cells from the linings of the kidney tubes that are present in urine, converts its source cells into neurons and glia cells via a more direct route, making the process more efficient while narrowing the margin of error.

In their study, the researchers harvested kidney cells from the urine samples of three human donors and converted the cells directly to neural progenitors. Rather than using a genetically engineered virus to reprogram the cells, they used a small piece of bacterial DNA that can replicate in the cellular cytoplasm, a technique that eliminates the need to tamper directly with the chromosome (in theory, at least, this should reduce mutations) while also speeding up the entire process. After growing their progenitors into mature neurons and glial cells, the researchers transplanted the progenitors into the brains of newborn rats. A month later, the cells were still alive in the rats’ brains, though it is not yet clear that they can survive for extended periods or mesh with the brain’s wiring to become functioning parts of the neural machine.

There’s still a lot of research to be done on this method of course, but the researchers think it may provide a way to take cells gathered non-invasively and quickly and efficiently convert them into neural cells while reducing the likelihood of genetic mutations.

http://www.guardian.co.uk/science/neurophilosophy/2012/dec/09/turning-urine-into-brain-cells

 

Mother-Child Connection: Scientists Discover Children’s Cells Living in Mothers’ Brains, Including Male Cells Living in the Female Brain for Decades

On By A.P.In Alzheimer's disease, bond, breast cancer, Chimera, chimerism, Communication, DNA, fetus, human, immune system, Microchimerism, mother-child connection, multiple pregnancies, Multiple Sclerosis, Nature, Neuropsychiatric Disease, Neuroscience, neuroscientist, nursing, Placenta, Pregnancy, Relationship, Science, Scientific American, stem cells, The Brain, twinsLeave a comment

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The link between a mother and child is profound, and new research suggests a physical connection even deeper than anyone thought. The profound psychological and physical bonds shared by the mother and her child begin during gestation when the mother is everything for the developing fetus, supplying warmth and sustenance, while her heartbeat provides a soothing constant rhythm.

The physical connection between mother and fetus is provided by the placenta, an organ, built of cells from both the mother and fetus, which serves as a conduit for the exchange of nutrients, gasses, and wastes. Cells may migrate through the placenta between the mother and the fetus, taking up residence in many organs of the body including the lung, thyroid muscle, liver, heart, kidney and skin. These may have a broad range of impacts, from tissue repair and cancer prevention to sparking immune disorders.

It is remarkable that it is so common for cells from one individual to integrate into the tissues of another distinct person. We are accustomed to thinking of ourselves as singular autonomous individuals, and these foreign cells seem to belie that notion, and suggest that most people carry remnants of other individuals. As remarkable as this may be, stunning results from a new study show that cells from other individuals are also found in the brain. In this study, male cells were found in the brains of women and had been living there, in some cases, for several decades. What impact they may have had is now only a guess, but this study revealed that these cells were less common in the brains of women who had Alzheimer’s disease, suggesting they may be related to the health of the brain.

We all consider our bodies to be our own unique being, so the notion that we may harbor cells from other people in our bodies seems strange. Even stranger is the thought that, although we certainly consider our actions and decisions as originating in the activity of our own individual brains, cells from other individuals are living and functioning in that complex structure. However, the mixing of cells from genetically distinct individuals is not at all uncommon. This condition is called chimerism after the fire-breathing Chimera from Greek mythology, a creature that was part serpent part lion and part goat. Naturally occurring chimeras are far less ominous though, and include such creatures as the slime mold and corals.

 Microchimerism is the persistent presence of a few genetically distinct cells in an organism. This was first noticed in humans many years ago when cells containing the male “Y” chromosome were found circulating in the blood of women after pregnancy. Since these cells are genetically male, they could not have been the women’s own, but most likely came from their babies during gestation.

In this new study, scientists observed that microchimeric cells are not only found circulating in the blood, they are also embedded in the brain. They examined the brains of deceased women for the presence of cells containing the male “Y” chromosome. They found such cells in more than 60 percent of the brains and in multiple brain regions. Since Alzheimer’s disease is more common in women who have had multiple pregnancies, they suspected that the number of fetal cells would be greater in women with AD compared to those who had no evidence for neurological disease. The results were precisely the opposite: there were fewer fetal-derived cells in women with Alzheimer’s. The reasons are unclear.

Microchimerism most commonly results from the exchange of cells across the placenta during pregnancy, however there is also evidence that cells may be transferred from mother to infant through nursing. In addition to exchange between mother and fetus, there may be exchange of cells between twins in utero, and there is also the possibility that cells from an older sibling residing in the mother may find their way back across the placenta to a younger sibling during the latter’s gestation. Women may have microchimeric cells both from their mother as well as from their own pregnancies, and there is even evidence for competition between cells from grandmother and infant within the mother.

What it is that fetal microchimeric cells do in the mother’s body is unclear, although there are some intriguing possibilities. For example, fetal microchimeric cells are similar to stem cells in that they are able to become a variety of different tissues and may aid in tissue repair. One research group investigating this possibility followed the activity of fetal microchimeric cells in a mother rat after the maternal heart was injured: they discovered that the fetal cells migrated to the maternal heart and differentiated into heart cells helping to repair the damage. In animal studies, microchimeric cells were found in maternal brains where they became nerve cells, suggesting they might be functionally integrated in the brain. It is possible that the same may true of such cells in the human brain.

These microchimeric cells may also influence the immune system. A fetal microchimeric cell from a pregnancy is recognized by the mother’s immune system partly as belonging to the mother, since the fetus is genetically half identical to the mother, but partly foreign, due to the father’s genetic contribution. This may “prime” the immune system to be alert for cells that are similar to the self, but with some genetic differences. Cancer cells which arise due to genetic mutations are just such cells, and there are studies which suggest that microchimeric cells may stimulate the immune system to stem the growth of tumors. Many more microchimeric cells are found in the blood of healthy women compared to those with breast cancer, for example, suggesting that microchimeric cells can somehow prevent tumor formation. In other circumstances, the immune system turns against the self, causing significant damage. Microchimerism is more common in patients suffering from Multiple Sclerosis than in their healthy siblings, suggesting chimeric cells may have a detrimental role in this disease, perhaps by setting off an autoimmune attack.

This is a burgeoning new field of inquiry with tremendous potential for novel findings as well as for practical applications. But it is also a reminder of our interconnectedness.

http://www.scientificamerican.com/article.cfm?id=scientists-discover-childrens-cells-living-in-mothers-brain