A reader recently asked about the cancer-causing potential of a skincare product she purchased from a company in Singapore (CALECIM). It contains laboratory culture-derived bio-signaling molecules derived from red deer umbilical cord stem cells. The product and cancer-causing potential are discussed below after a brief review of the field in general.
Skincare products containing conditioned media from laboratory human cell cultures date back two decades. The first product of this type, TNS, is still marketed by SkinMedica, a company since purchased and owned by Allergan. In March 2014, a class-action lawsuit was filed against Allergan alleging that the lead plaintiff (and others in the class) had paid too much for a product that had “potential” to negatively impact skin health including possibly inducing or promoting cancer.
Of great interest, and typical of “greenmail” lawsuits filed to coerce monetary settlements, no proof or evidence was offered that supported the cancer claim. Nothing at all. The plaintiffs’ claim was they paid too much for the product, not that it was dangerous. We are not aware of any instance where cell culture-derived ingredients in any topical skincare product have been implicated, let alone proved, to cause or promote skin cancer. After litigation that lasted three and a half years, the case was dismissed with prejudice (meaning it cannot be refiled).
As is almost always the case, the terms of this dismissal between the parties were not disclosed. If money changed hands, and it most assuredly did, you’ll never know how much was paid to make this frivolous lawsuit to go away. Legal firms that specialize in class action greenmail lawsuits make millions of dollars each year this way. Understandably, they always go after a “deep pocket” defendant, an entity or person with lots of money. That’s an essential part of the greenmail business model. No money, no payout from the greenmail lawsuit is possible, so why bother.
Cell Types Matters a Lot.
TNS contains conditioned media from the laboratory culture of fibroblasts obtained from foreskins of circumcised newborn male infants. We have been critical of this use of fibroblasts elsewhere on BFT because these cells are extremely poor producers of growth factors and cytokines. Such bio-signals are essential for life itself and involved in intercellular communication in all complex organisms. There is a very long and extensive history of safety with many millions of units of such products being used by millions of consumers.
We have been critical of other products that contain bio-signals derived from laboratory culture of human cells, usually focused upon the potential pro-inflammatory nature of the net “pattern” of secreted bio-signals, i.e. the growth factors, cytokines and other proteins produced in culture. While it is well known that chronic inflammation is itself a contributing causative factor for some cancers, we are unaware of instances where topical skincare products have been implicated in this way.
For our products, which are based on the culture of bone marrow mesenchymal stem cells, there is abundant evidence that these cells produce bio-signals with a net anti-inflammatory pattern. (For balance, and for a different opinion, one that we do not share in the least, we direct you to our recent two BFT posts on scientific misconduct in aesthetic medical research.)
Two decades later, many types of cells have been cultured in order to obtain bio-signals for skincare products. Human stem cells from bone marrow, fat, and embryos are but a few. This post resulted from a reader’s question about the safety of a product called CALECIM, for which the stem cell source is umbilical cords obtained at the time of birth of red deer. We are also aware of products containing ingredients derived from stem cells from sheep placentas.
Similarities and Dissimilarities of Normal and Cancerous Cells
In order to maintain viability, including the ability to grow and divide, all cells must have continuous access to metabolic fuel and oxygen to produce cellular energy and survive. In the most abstract sense, then, proteins, fats, carbohydrates, and oxygen are capable of being “hijacked” to promote cancerous cellular growth.
Differences in normal and cancer cellular characteritstics include nuclear and cytoplasmic volume, cell shape and conformity, the presence or lack of normal specialized cellular structures and markers, clearly or imprecisely defined boundaries, and the relative number of actively dividing cells.
What about Plant Stem Cells?
We long ago poo-pooed plant “stem cells” in skincare products because plant and animal bio-signals are not interchangeable. They speak entirely different biologic “languages.” Animal cell receptors are not configured to respond to plant messaging molecules and vice versa. Plants do indeed have abundant value in skincare and have had for millennia. Their “stem cells”, however, aside from possible antioxidant effect, do not. You can learn more at:
Formulators and marketers are always looking for something new to sell, whether or not they make scientific sense. The use of red deer umbilical cord stem cells may have a lot to do with the fact that the same company has long produced products produced from red deer antler velvet. These are sold as “supplements”, as has been common in traditional Asian medicine for centuries.
The transition to umbilical cord stem cells is cheap and easy, especially when compared to the expense and complexity of obtaining human umbilical cords. The herds of red deer are already in place and well managed. An equally important consideration, or perhaps the most important consideration, is Europe, China and other parts of Asia do not permit us of human stem cell-derived ingredients in cosmetics. By contrast, in Singapore, animal-derived stem cell mediums are allowed for use in cosmetics. Politics possibly? Perhaps.
Interestingly, their co-founder and chief scientific officer, Dr. Phan Toan-Thang, described the epithelial stem cells within the umbilical cord as capable to “transform into skin tissue” and the “mesenchymal stem cells as important for bone and organ repair.” He added that “stem cells are notoriously difficult to harvest from other body parts, such as the bone marrow, adipose fat layers, and placenta.”
The brand name, CALECIM, was coined using the first letters of the four words “cord”, “lining”, “conditioned” and “media”, along with intervening vowels.
Published Study Evaluating Product Efficacy
A split-face three-month trial involving 40 healthy subjects with moderate to severe facial wrinkling secondary to photodamage was performed, comparing a product containing red deer umbilical cord stem cell conditioned media to the vehicle cream without conditioned media. Objective evaluations by study investigators were performed in a double-blind fashion. Subjective evaluations were performed by each study participant.
The study can be seen at: https://pubmed.ncbi.nlm.nih.gov/31012565/
Results were Mixed
“Blinded investigator assessments did not detect any statistically significant differences between the two halves of the face in terms of efficacy, safety, or tolerability.”
“Subject evaluations demonstrated the superiority of the active treatment side.”
Observations within the Summary of the Article Text
“There was no statistically significant change in the degree of wrinkling or elastosis in either sides of the face throughout the study (P<0.5).”
“Comparing the two sides of the face, there were no significant differences in the percent improvement between the active cream and vehicle in wrinkling, laxity, dyschromia, erythema, or texture.”
“Looking at the overall improvement percentage at week 6, patients using the active cream showed an average improvement of 13.15%, with similar improvement of 13.15% in subjects using the vehicle (P=1.0).”
“At week 12, average improvement of patients using the active cream was 27.7%, while patients using the vehicle showed an average improvement of 22.9%”
Based on conflicting objective and subjective study data, BFT finds it difficult to agree with the conclusion offered within the published study abstract:
“Conclusion: Red deer umbilical cord lining mesenchymal stem cell extract was effective in rejuvenating the aging face as demonstrated by investigator and subject measures.”
Disease Transmission Risks with CALECIM
We have been informed through inquiries to the company in the past that “red deer do NOT have transmissible pathogens whereas sheep (scrapie) and cattle (bovine spongiform encephalopathy) do.”
Our research disputes this conclusion. Deer indeed do carry zoonoses (transmissible animal diseases.) There is no evidence that these products are screened for any of these diseases or that, to the best of our knowledge, anyone has contracted any illness from use of CALEMCIM. In contrast, a human who donates cells or tissue for laboratory culture or transplantation is thoroughly monitored and tested.
Details can be seen at the URL below. (Note – cervids is the animal family that includes all types of deer, among other similar type animals)
Of particular note, perhaps, is the burgeoning prion epidemic or deer, elk, reindeer, and moose known as chronic wasting disease, or zombie deer disease. As a generality, this is a prion condition similar to bovine spongiform encephalopathy, or mad cow disease, that was a worldwide concern in the 1980s and 1990s.
Based on the disparate nature of the objective and subjective data, BFT does not share the study abstract conclusion that the efficacy of CALECIM is proved.
Our opinion is that cancer risks are negligible, similar to other skincare products containing laboratory cell culture-derived ingredients. We would add that applies to all products in this class, including those manufactured by the company co-founded by your BFT hosts.
While risk of transmission is likely extremely low, we cannot agree with the conclusion provided by the company to us in private communications that red deer do not have transmissible pathogens. It is likely, however, that the “captive” herd from which CALECIM ingredients are obtained may indeed be disease free.
Apologies for going off topic, but you guys have been very helpful with Anteage questions in the comments. What’s the shelf life on the Anteage Serum and microneedling solution? And would they both last even longer in the refrigerator?
Tim, we get a fair amount of our questions on BFT from readers wanting to know more about the AnteAGE and AnteAGE MD products we have developed and market wearing our daytime hats as founders of Cellese Regenerative Therapeutics. To help maintain a clearer line between our BFT and commercial duties, let us refer you to the best place to get your questions answered. There is staff on duty every weekday to help you. Voicemail can be reached at (877) 350-6350. Email should be sent to: email@example.com
I use AnteAGE MD products and microneedle regularly, which helps me hide my very middle age. Today I have questions about two products: 1) the brand Oneskin, which claims to reverse skin ageing by killing off zombie cells, and 2) the Droplette device (I have one) which claims to break particles into nano-size droplets and spray them into the epidermis (I don’t see any difference in my skin yet.) Can you help me understand these products?
#1 – One Skin
One Skin claims to have developed a “topical supplement” for skin based on proprietary technology they call OS-01, which was developed by four female PhDs. The purported targets of the ingredient are senescent cells within the skin. These are the aged cells no longer capable of replication that are recognized contributors to tissue inflammation. No details are given about OS-01 except that it is a proprietary peptide tested on 3-D skin models and skin on humans . Marketing verbiage on the One Skin website includes the hyperbole we’ve seen with other products that claim revolutionary breakthrough technologies: “The first topical supplement designed to extend your skinspan on a molecular level.” The website states that their product has produced benefits in clinical trials, presumably conducted by them. We could find no published data about the product improving skin although the actives in the ingredient deck include well known compounds with abundant proof of efficacy in past studies by others. Nothing, however, about OS-01 that we could find. One Skin also contains the additional peptide Decapeptide-52, along with botanical antioxidants, niacinamide, and tocopheryl acetate.
From the Skin One website:
“Through our clinical studies, OneSkin discovered its ability to reverse the biological age of one’s skin by reducing the main drivers of inflammation that lead to skin cell malformation and death (i.e. wrinkles, loss of elasticity, and aging skin).”
A PubMed search does return a 2020 published article authored by these four individuals dealing with identification of DNA methylation to validate therapeutics for healthy aging. (Citation below).
Boroni M, Zonari A, Reis de Oliveira C, Alkatib K, Ochoa Cruz EA, Brace LE, Lott de Carvalho J. Highly accurate skin-specific methylome analysis algorithm as a platform to screen and validate therapeutics for healthy aging. Clin Epigenetics. 2020 Jul 13;12(1):105.
#2 – Droplette
As the Droplette website explains, the Droplette micro-infuser “is a physics-powered device that transforms skincare ingredients capsules into a powerful micro-mist, allowing for the delivery of skincare deep into your skin.” The website further explains, other “facial mists exist…but the particles are large and slow, pooling on the skin.” They claim the “device delivers ingredients deep into your skin” whereas over 90% of topicals (such as creams or serums) just sit on top of your skin with the actives never actually absorbed into your skin.Their argument is that the barrier effect of the stratum corneum prevents molecules larger than 500 Daltons from penetrating the skin. While generally true, published methods of improving penetration detail numerous ways to do just that.
The Droplette device employs a pump and piezo to create a “micro-mist” in which water-borne actives are present. Because the skin surface is hydrophobic due to the presence of sebum, ceramides, cholesterol and free fatty-acids, even aqueous micro-mist seems unlikely to easily penetrate. Call us skeptical, perhaps even doubtful.
Trommer H, Neubert RH. Overcoming the stratum corneum: the modulation of skin penetration. A review. Skin Pharmacol Physiol. 2006;19(2):106-21. doi: 10.1159/000091978. Epub 2006 May 9. PMID: 16685150.
Haque T, Talukder MMU. Chemical Enhancer: A Simplistic Way to Modulate Barrier Function of the Stratum Corneum. Adv Pharm Bull. 2018 Jun;8(2):169-179. doi: 10.15171/apb.2018.021. Epub 2018 Jun 19. PMID: 30023318; PMCID: PMC6046426.