In March 2019, BFT introduced our readership to a remarkable class of intercellular signaling messengers called exosomes. These are extraordinarily small “packets” of potent bio-signaling molecules secreted by all types of cells which migrate near and far within body fluids to dramatically influence the behavior of target cells. Exosomes are miniscule double-layered lipid “envelopes” containing cytokines, chemokines, DNA, RNA, micro-RNA (miRNA), and other proteins which is collectively described as their “cargo”.
The contents of exosomes are determined by the genetic machinery of the cells from which they originate. Stem cells are the most prolific producers of exosomes and most of stem cells’ effect and influence upon physiologic processes and cellular behavior is the direct result of the exosomes they produce. Indeed, recent research, including studies addressing ARDS (acute respiratory distress syndrome) caused by COVID-19, are using mesenchymal stem cell-derived exosomes (administered intravenously) in lieu of actual stem cells. Results of these studies and others reveal exosome potency and efficacy rivaling that of stem cells without the potential downsides of stem cells including attack and destruction by the recipient immunologic system, or possible tumorigenesis. Such efficacy bolsters the premise that stem cells perform their functions, not by differentiation into specific types of cells, but rather through the secretion of bio-signals that modulate inflammation and “instruct” other types of cells to perform particular functions.
MARKETERS NEVER FAIL TO TAKE NOTICE
Just as the term “stem cell” was long ago purloined and misused by many marketers in the cosmetic and esthetic fields, we are now seeing more and more examples of misuse of the term “exosome.” So, our word to the wise: grab your wallets tightly and know what you are buying before you fork over your hard-earned money on products that allege that they contain exosomes. Some may, and more will eventually come to market that actually do contain exosomes, but most products currently touting exosomes contain none. Or, at a minimum, none that are intact. We explain below.
Several of BFT’s earlier posts directly addressed the misuse of terminology to confuse consumers. It has been a massive pet peeve of DrJohn and DrGeorge from the day BFT was launched. When it comes to misinforming consumers, who through no fault of their own lack the scientific background to know fact from fiction, there are no white lies. If the effort is to sell product by telling a marketing “story” that is not scientifically accurate, to your hosts such white lies are black as night.
CONDITIONED MEDIA CONTAINS EXOSOMES BUT NOT AFTER PRODUCT FORMULATION
Over the past several years, BFT pages have discussed a variety of products that contain conditioned media, including brands developed and produced by your hosts. Conditioned media is the nutrient broth in which cells are cultured in the laboratory, after all cells and cell debris have been removed by ultrafiltration. Contained in conditioned media are all the biosignals secreted by the cultured cells including the exosomes produced. So, theoretically, products that have conditioned media as one of their ingredients do contain exosomes, or more correctly what used to be exosomes prior to mixing, emulsification and blending of other ingredients. As pointed out here and elsewhere on BFT, exosome cannot remain intact under such conditions. Is the cargo of the exosomes within the final product? Sure, but assuredly not in the concentrated form it is within exosomes. That cargo is dispersed and uniformly mixed with other ingredients. To claim these products contain exosomes is verbal sleight of hand and a disservice to the consumer. The reason is simple.
Exosome products, if they actually do contain intact exosomes, cannot be found within this type of product. Exosomes are technically challenging to concentrate, separate, and preserve in a form suitable for therapeutic use. Such concentrated forms of exosome products are possible and available but currently very limited in number and very expensive. Progress is underway to develop scale up of such processes but for now, the time and equipment required dictates that final product prices be prohibitive to all but the affluent. Any $40 jar of moisturizer, claiming to contain “more than a million and a half exosomes”, as one brand does, is a ruse. Save your money; don’t buy it. True exosome products, with intact exosomes, will not come in a jar of moisturizer, and they will contain billions of exosomes in a very small volume. These products also will not be intended for home use by topically slathering them on the skin. Expect them to be used in conjunction with microneedling or mesotherapy (multiple closely placed injections of small amounts into the dermis.) Exosomes may be preserved and marketed in either frozen or lyophilized forms. Freezing must be at very cold temperatures, much lower than home freezers can provide. Lyophilizing is the scientific term for freeze-drying.
(FYI: Your BFT hosts are currently in the process of developing true exosome products that will be affordable.)
“TRUST BUT VERIFY”
BFT was interested in what is available in the marketplace that purports to contain exosomes. An internet search for “exosomes in skincare” was instructive and produced results that once again confirm our opinion that many marketers aren’t interested in educating the public, they just want their money. How’s this for solid-science messaging?
“Bio-digital” products contain exosomes that “sync” cells to lock in hydration and radiance.
Internet searches also indicate that prestigious clinics in America are offering “Exosome Facial Rejuvenation” procedures, typically in conjunction with microneedling. One describes it as a “high-tech beauty treatment to resurface and fractionate the skin’s texture.” Not sure how the verb “fractionate” should be defined in this context, but it does sound like high science, right?
As part of our work in exosome research, we have access to equipment capable of characterizing and determining the size of particles in solution. We did that with two products currently available on the market, one from South Korea and another produced in the United States. The South Korean product is lyophilized, the American product frozen. The results are interesting.
Exosomes are 30-150 nm (nanometer) in size, or about 1/1000 the size of a typical cell. As the graph above demonstrates, the Korean “exosome cocktail” contains particles that are mostly 200 nm in size or larger. Based on size criteria, this relatively inexpensive product appears to not contain exosomes at all. This product arrived at room temperature in powder form.
The American product appears to contain relatively high concentration of exosomes, with most measured particles falling within the definition size of 30 to 150 nm. We tested the smallest volume product available which has a price tag of more than $600. The price of other products from this company is even higher.
EXOSOME PRODUCTS ARE COMING
Research in the exosome field is expanding rapidly with the majority of it focused on applications within the medical field including diagnosis, prognosis, and treatments of a myriad of diseases and conditions. Exosome breakthroughs will also inevitably find application in medical esthetics, particularly as adjuvants useful in skin and hair follicle procedures. It is anticipated their impact and benefit will rival and potentially surpass that of stem cells.
Click here to read BFT’s first exosome post: EXOSOMES – very small, very mighty, very important
Hi, what do you think of the brand Benev by Exocobio on the subject of exosomes?
We have access to testing equipment that can examine products for the presence of nanosized particles. Recall that exosomes, by definition, are extracellular secreted vesicles sized 30 to 150 nanometers. The Benev “exosome” product was tested. It is a powdered (lyophilized) powder that comes with a 5cc vial of diluent. It was tested after reconstitution and no particles within the exosome size range were identified. The majority of particles were 200 nanometers and larger in size. Exosomes? Doesn’t comport with our test results using equipment that is routinely used to identify and quantify exosomes in solution. We have our doubts about the Benev product.
Are you familiar with the brand Droplette and if so what do you make of them?
We addressed this recently so this is a repeat.
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.
Do you have any thoughts on this exosome serum?:
After reviewing this website, it seems the product may be primarily conditioned media produced by stem cells in culture. Conditioned media contains exosomes although to tout that as the primary ingredient would seem, at least to us, to imply there has been some effort to isolate and concentrate the exosomes. This is possible although an expensive and time-consuming process. We would also expect such a product to be frozen from the time of production, or possibly lyophilized (freeze-dried). So you know, we have analyzed two so-called exosome products from South Korea and the USA. One had nary an exosome to see, and the other had particle size data that showed most contents were too large to be accurately called “exosomes”. Also, the Infinivive product seems to simply be topically applied with no other methodology employed to enhance or enable skin penetration. Call us skeptical although we are convinced exosomes may one day have a role to play in skin rejuvenation, most likely with techniques involving microneedling or intradermal injection.
I love this blog and thank you so much for taking time to answer our questions. There is a brand called Osmosis that has a product called Osmosis Beauty StemFactor – Growth Factor Serum. I’ve put a link to it below.
They claim they have exosomes, and also that they use the conditioned media as well. I’m pretty wary about this product, but I’m curious if you have reviewed it in the lab?
We are familiar with the Osmosis brand and their use of a combination of conditioned media derived from two types of human cells – fat (adipose derived) stem cells and fibroblasts. As you may know, anytime one harvests conditioned media from a cell culture, regardless of cell type, all secreted molecules and structures secreted by the cells are recovered. Because all cells produce exosomes, conditioned media will contain exosomes from the cells. When products are produced with conditioned media as an ingredient, all secreted substances will be contained as part of the product. Intact exosomes, however, would be impossible to isolate because of the process of making a serum and the other ingredients in the product. Exosomes are delicate and easily disrupted, spilling their contents into the mixture to which they have been added. Everything within the exosomes (RNA, lipids, proteins, GFs, Cytokines, etc.) will be in the final mixture, but not contained within exosomes. That said, every product produced using conditioned media could rightfully but not accurately claim, that they conation exosomes. To obtain intact exosomes in any significant concentration, conditioned media must undergo ultracentrifugation (using up to 200,000 times gravity) or subject to tangential flow over a series of filter membranes with increasingly smaller pore sizes. The exosomes then must be frozen at extremely low temperatures, or freeze dried. Our opinion is Osmosis is using the term “exosomes” much more as a marketing buzzword than a true description of the product. Happens all the time.
When can we expect your exosome product to be available?
Our research efforts continue. More than a decade of culturing stem cells has provided extensive data as to what constitutes the secretome of a cell line in culture, and ways to influence the secretome. What we find amazing yet consistent with the “sell the sizzle, not the steak” mindset of cosmeceutical marketing, is the increasing number of companies claiming they have “exosomes” in their formulation. OK, we’ll agree that all conditioned media from all cells, regardless of cell type, does contain exosomes, or at least what could once be called exosomes. However, when formulated in any type of emulsions or multi-ingredient formulation, all exosomes will lyse, or be destroyed. Granted, their contents will remain in the product; intact exosomes will not. Our approach is to develop the means to produce and deliver to the customer, a formulation that retains the exosomes in concentrated form. That will require freezing or lypholyzing the exosomes after they have been substantially “concentrated”, not an easy task. BTW, we’ve looked at different products claiming to contain exosomes. Some do but with a very high price tag. Others, nary an exosome in sight.
Stay tuned. We are working on this project in earnest. We’ll have news when we develop and validate a method that will enable us to say: “Exosomes inside, and we mean it”.
What do you think of “Enfinity” serum from Elevai with exosomes derived from Human Umbilical Mesenchymal Stem Cell Conditioned Media?
The product appears to have several proven active ingredients in addition to their claim of containing exosomes. As we’ve discussed elsewhere of BFT, simply stating the product contains “exosomes” is not always an accurate descriptor. Conditioned media, regardless of the cell from which it is derived (umbilical stem cells have significant published proven clinical utility) always includes the exosomes secreted by the cells. Keeping exosomes intact in products, however, is nearly impossible unless specific methods are used. We find their claim of containing “exosomes” likely similar to other products making the same claim. If they claim the exosomes are intact, we are extremely doubtful; if they mean the product contains the contents the exosomes originally had within them, we can agree. Intact exosomes? Well nigh impossible unless specific methods of preservation are utilized. See the references below where frozen storage at -80 degree centigrade and lypholized (freeze dried) methods are described.
Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P. Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications. Int J Nanomedicine. 2020 Sep 22;15:6917-6934.
Kusuma GD, Barabadi M, Tan JL, Morton DAV, Frith JE, Lim R. To Protect and to Preserve: Novel Preservation Strategies for Extracellular Vesicles. Front Pharmacol. 2018 Oct 29;9:1199. d
Charoenviriyakul C, Takahashi Y, Nishikawa M, Takakura Y. Preservation of exosomes at room temperature using lyophilization. Int J Pharm. 2018 Dec 20;553(1-2):1-7.
I’ve recently purchased a growth factor and cytokine serum. I’ve emailed the customer service at that company and I would like an answer from you guys. Does Tretinoin counteract and/or render ineffective any of the ingredients in Anteage serum? Can I use the two together? And if so, simultaneously the same night?
Very few ingredients are rendered “ineffective” in skin care products due to other ingredients. The caveat is that each ingredient does not alter the pH in either direction sufficiently to affect how the molecules in the ingredient exist (for chemistry geeks, the effect of pH on pK). This is also important to prevent amino acid peptides, growth factors, and cytokines from molecular “attack. This applies to retinoids of all types, including tretinoin, which are all molecularly related to vitamin A, and proven to promote collagenesis. Depending on skin sensitivity and concentration in the product, tretinoin can produce side effects that include redness, dryness and flaking. We opted to include a botanical based retinoid in our formulations that has vitamine A effect, but without the side effect.