Stem Cells and Skin Part 3: It's the Cytokines | BareFacedTruth.com

Stem Cells and Skin Part 3: It's the Cytokines

As human stem cells and their role in skin physiology, wound repair, aging, and rejuvenation is the subject of our own work, we have a lot to say on the subject. As our goal here is education at a consumer level, we struggle mightily to express complex concepts and research results in terms that can be appreciated by all, including non-scientists. But sometimes fine shades of meaning have big consequences, and we don’t want to compromise on the bare faced truth mission either.  It is frankly a challenge, and I’m sure we fail for the most part. So we apologize in advance and ask you to bear with us. Hopefully we will get better at this as time goes on.

In a prior post we introduced the subject of mesenchymal stem cells. Next we will take you a bit further down the path of understanding what these particular stem cells have to do with skin and aging. I thought I would put this in outline form. See if this makes it any easier to digest. Here goes.

Not all stem cells are the same. There are many varieties.

Mesenchymal stem cells (MSC’s) are one type; they form a key part of the human body’s defense against injury and stress.

MSC’s can be found in many places in the body – bone marrow, fat, tooth roots, around blood vessels, etc. Each of these are called “niches” and reflect the home environment of that type of MSC. There is increasing evidence that marked differences exist in the biology of MSCs that are dependent on the tissue of origin. Indeed this niche factor  appears to be the main source of variation in the biological properties of MSCs (De Bari et al., 2008; Augello, Kurth & De Bari, 2010).

Thus, not all MSC’s are the same.

MSC’s migrate to damaged areas of the body. There they act as first responders. Their primary role is command and control – telling local tissue what to do, and organizing cells of the immune system which are the worker bees.

All communication among MSC’s and between MSC’s and other cells (e.g. damaged skin cells) uses biochemicals called cytokines.

There are hundreds of cytokines, each with a specific message (e.g. “hey fibroblasts, let’s make some more collagen”). Multiple messages are in play at any time in an MSC mediated response. The messages are tightly coordinated so they reach the right cells at the right time for the proper work to be done. Some are very short distance and some are medium or long distance.

Cytokines can be classified into families. Some are growth factors (“make more cells”), some are chemokines (“bring me some phagocytic cells”), and many are involved in protein synthesis inside cells they target.

MSC cells themselves can differentiate into needed cells for rebuilding damaged tissue. But it turn out that that is a minor part of what they do,  not the major thing.  In skin in particular, MSC’s as bricks in rebuilding is unlikely except in severe damage (e.g. burns).

Aging skin reflects both intrinsic cell and tissue level changes (senescence) and a process of continual damage (e.g. from sun, chemicals, disease) and repair (via several mechanisms, including calling 911 to bring MSC’s to the area).

There are unique MSC-like cells that live in very small numbers in the bottom of hair follicles. This is their “niche” (remember, not all MSC’s are the same). There are also perivascular (around blood vessel) MSC’s in the dermis of skin (deeper).

These “local” stem cells have particular roles to play in maintenance of growth, and replacing senescent cells (all cells die of old age eventually). But in terms of damage, other MSC’s migrate to the area from guess where? The bone marrow. Seems like that is the special role of that particular MSC niche.

That scenario will be no surprise to those who know that the bone marrow is also where all the blood cells (red corpuscles and white immune system cells) are made and exported via the blood stream to perform functions throughout the body. In fact, bone marrow MSC’s and bone marrow “hematopoetic” stem cells live in very close proximity in the bone marrow. These are the same cells that get replaced when a “bone marrow transplant” is performed.

When skin undergoes repair, all these mechanisms must act together in a coordinated fashion. Again, that control seems to be the specialty of marrow-derived MSC’s secreting very specific patterns of cytokines. Those cytokine patterns are what determines that the right thing happens at the right time. E.g. you don’t want to build new cells until you have mopped up the debris from damaged tissue. That would be like painting over old peeling wallpaper. Ask your local contractor. Demolition happens first, then rebuilding.

When you hear about products that contain stem cells, you should ask several questions. First, you should read Dr. George’s post about plant stem cells (don’t work), creams that have nothing to do with stem cells whatsoever except using it as a deceitful marketing term (e.g. Biologic’s Stem Cell Cream). You can filter these out right away.

 

That leaves you with human stem cells. Now, you will not find cosmeceutical products on the market that contain human stem cells. That would be considered a “biologic” by FDA standards, and would be regulated like a drug or device. The reason is that whole cells contain (other people’s) DNA, and may also carry disease.

While human stem cells themselves won’t be in any products, they can be grown in culture (in vitro, or outside the body) in a laboratory. When they do so, if they are well fed and happy, they tend to divide to make new daughter cells. When they are doing so, they communicate with one another via cytokines. Remember the messenger molecules we spoke of above? This is the basic language of stem cells. Again, if the conditions are right, they chatter away as they “expand” in culture (more of them, coming closer together”). As they start to crowd up against each other (we call that “confluence”) the message changes. More of those “short distance” cytokines are produced. Some are transferred from one cell to next one touching it (we call that a “paracrine” message). The MSC’s  start to slow down their proliferation when the numbers reach confluence. At this point the cell biologist may transfer some of those cells to new flasks, where they will be less crowded, and will resume proliferation. This is a called a “passage”.

Now, if you remove some of the nutrient rich fluid that bathes the MSC’s in culture, you will find that it contains a lot of cytokines. This is called conditioned medium. It is cell growth medium conditioned by the many cytokines secreted by the MSC’s. It’s like capturing a whole bunch of cell-to-cell conversations all at once. An analogy might be your cellular telephony system. If you could grab 5 second sample of all the conversations going through one cell tower, it would indeed be a “tower of babble” But your cell system is clever enough to sort all those words into the right pathway to make a conversation.

So, here is the discovery that led to a whole new generation of anti-aging skin care products. If you take that conditioned media and put it on skin, you can observe immediate improvements in skin texture, tone and color. If you keep applying it, you will see structural changes (increase collagen production) with diminution of wrinkles. It has interesting “side” effects.  Minor cuts  and abrasions heal very quickly. Angry red areas seem to disappear.

That defines the first generation products whose key active ingredients are made by stem cells in vitro. But that is only the start. We now are gaining insight into the stem cytokines themselves, and the patterns they form. We know that they talk about a lot more than growth, and if can discern what they are saying and how they say it (in other words decipher their language) we can change the cytokine composition of the conditioned medium. We can them communicate back with the MSC’s in culture in their language. In doing so (I will leave out a lot of proprietary steps here) we can get them to change their message by responding to ours. We can optimize it for different situations. So, it is no longer one product (a bunch of cytokines) but a very clever set of stem cells making products for whatever condition we require.

This is a lot for one post. I’m up to about 1,500 words. I will leave it here for now, and let interested folks who have read this far digest and ask any questions you may have.

One last thing – this is very exciting stuff, and has many impacts beyond skin & aging. This is not mere cosmetics – this is core cellular physiology. And how grand it is (for a change) that skin science gets to be on the forefront of research rather than on the back burner.

Await your comments.

Dr. John

86 Comments

  1. researcher.girl says:

    I have to say I find your topics enthralling. I’m not just looking for great skin care. I love to understand the mechanics. I’m usually the conduit for information for the people in my life because I want to know, and they want the results. I find the post to be easily understandable and not at all too lengthy. I believe there is a self selecting group who has gotten to your website. I originally linked here because I found truthinaging.com to be one of the more detailed oriented sites, but it has evolved more bias(as they have a right to be as a commercial site) as their deepening relationships with manufacturer’s provide their knowledge base. Much like many time compressed GP’s get the bulk of their data from drug reps. I believe the tutorials you provide have cleared a great deal of the chatter. As someone with a science background, I listen to various outlets for product information and sometimes I hear their spiel go off the deep end when they make some biologically implausible remark.

    • drjohn says:

      Thanks so much for the encouragement. We do need your moral support. Please do tell others about the site. We are trying to boost our search engine rankings, so if you know of any other sites that might feel inclined to link here please let us (and them) know. And please feel free to suggest topics, approaches, products to review, etc. Welcome to our small (but growing) family. Dr. John

  2. MacNot says:

    I have seen some products with “adipose derived stem cells”. Are they the same as marrow cells? Do these products work?

    • drjohn says:

      Your body’s fat stores contain stem cells that look a whole lot like the stem cells in your bone marrow. They have the surface markers of mesenschymal stem cells (MSC’s). But the statement in the post above … “There is increasing evidence that marked differences exist in the biology of MSCs that are dependent on the tissue of origin.” is a major key to understanding that there are important differences. They look the same, but they are not the same functionally. These MSC’s living in fat tissues are not the first responder cells mobilized for repair. That is not their “NICHE”. In fact, they may be part of a different system that has to do with regulation of fat (energy storage) biochemically as well as being progenitors for new fat cells (should you need more). Now, when expanding a colony of these cells in a culture (in vitro) they behave just as MSC’s (or fibroblasts, indeed many mammalian cells) in secreting cytokines to exchange information during growth. The focus of the message is growth. But it is not necessarily a recipe for repair and rejuvenation. Do they work? Yes. As well as marrow-derived MSC’s? Theoretically not, based on the logic derived from the latest knowledge about MSC niches. The placement of “damage control” MSC’s in bone marrow makes perfect sense teleologically. So much of their work has to do with immune cells being made there, in a place rich with blood vessels. Fat lacks that logic. Its like housing your big city emergency personnel in the country down a dirt road. The reason some companies use these cells is because they are easy to get (the disposed waste of a liposuction vs. a bone marrow aspiration). And therefore a lot cheaper. We will be looking at cytokine patterns in a future post, which will help to clarify this picture.

  3. Kristina says:

    Hi Docs,
    I was wondering about the DNA serums I keep seeing advertised. They claim to preserve your DNA as it is by keeping your telomeres from shortening any further and keep wrinkles at bay. Truth or hype?

    • drjohn says:

      Hi Kristina. We are planing a post in the near future on DNA related product claims. As with so many other things we have seen out there, there seems to be more hype than truth, and the products themselves make little sense. Scientists have been working with telomerase (an enzyme which actually preserves telomeres/DNA) for several decades. It’s not easy to get through the skin (its a big protein enzyme, and surface skin secretes it’s own proteases to prevent such things getting through) and if it does the problem is then getting it into living cells. It is normally made in the nucleus by the same DNA it is designed to repair. Researchers often use viruses to “infect” cells with the gene that makes telomerase. BTW -telomerase inhibitors are an anti-cancer strategy. I think you can probably see where this is going …. but there is actually some truly promising work going that we will be telling you more about. Stay tuned, and thanks.

      • Kristina says:

        Thanks so much!! These is the most helpful informative site I have ever encountered. Thanks for all your time and work.

  4. Drgeorge says:

    Kristina, we appreciate your kind words. Drjohn and I take our mission seriously. We want our readers to understand the science of skin, aging, and therapeutic possibiliies. There are too many instances where buzz words rule the day and the buying decisions. At least we can level the playing field by separating fact from fantasy. We hope you continue to join us in our dialogue and, please, invite others to stop by BFT and join in the conversation. Happy Holidays to you and yours.

  5. GW says:

    Hi,

    I was interested in Reluma, but now I have serious concerns. As I understand it, Reluma does not use the whole EGF protein (or whatever it is), but rather the run off or kind of soup from several EGFs. Above, I think you said that Marta reported that Reluma uses 9 EGFs. Regardless of the actual number, are you saying that each EGFs cytokine needs to be included for product safety?

    Thanks for your patience and I look forward to your primer on collagen & elastin physiology.

    GW

    P.S. It is a shame TIA will not agree to work with you. I really think TIA could turn it around without admitting any wrongdoing. Since their following is large and devoted, a new TIA could help many women. I remember when I first started to read TIA, several warning flags went up—selling products, evaluation procedures, and the lack of credentialed testers. However, for a while, my vanity and their good writing skills helped me to push facts out of my mind. However, eventually Research Methods I crept back into my mind and hope it will for other readers as well.

    • drjohn says:

      Hi GW,

      Yeah, Marta said nine, but the serum actually contains “387 growth factors” according to their web site. But even that is confusing because they are really talking about cytokines, of which only a handful are growth factors. The truth is there are probably even more, because the actual active ingredient is “conditioned medium of adipose stem cells”. You can read all about what that is in our stem cell cytokines post. Now EGF is one of those hundreds of cytokines, and one that is a growth factor, but it is balanced by the other cytokines of the “soup” so that it’s particular effects cannot get out of control. Stem cells are all about maintaining homeostasis during growth. So, I wouldn’t have any concerns about its safety. If you dig further in our post, you will notice that I do question the efficacy of adipose derived cytokines vs. those of bone marrow mesenchymal stem cell (MSC) origin. Adipose MSC’s (their niche is obviously fat tissue) are important in cosmetic implants because they are easy to get from liposuction. But for powerful chemical factories of growth and repair, they are a little on the “sleepy” side compared to marrow-derived MSC’s. These are the ones you read about being used for heart attack recovery, etc, with spectacular results. But harder to get, more demanding in culture.

      Your thinking about “a new TIA could help many women” inspires us. We have the vision as you, but TIA sadly rejected the intrusion of real science. We are actively searching for a “user experience” oriented site to partner with, or someone with the passion to get one started. For us, selling products is not the issue. We develop products ourselves (although we are notoriously fussy, so they take a while). We want people to try and use great products. It’s about getting the science right, even when the waters are murky, which they often are. So if you know of someone, please send them our way.

      Thanks so much for your insightful comments. Dr. J.

  6. ChicGeek says:

    Before I read about cytokines, I had the “stem cells” craze pegged as utter nonsense. Other people’s mashed-up skin cells? If any of their biological matter could penetrate, it’d call that a VERY BAD IDEA. Inflammation would only be a start. There’s a reason we do donor matching followed by powerful immunosuppressive drugs for the rest of a transplant recipient’s life!!!!

    Since then, though, I’ve been intrigued–but very skeptical of most products on the market.

    Is there a molecular difference in the structure of cytokines from MSCs from marrow versus adipose tissue? Or is it simply concentration in the conditioned medium at the time of division in the lab? Basically….HOW are cytokines from bone marrow-derived MSCs better than adipose MSCs?

    • drjohn says:

      Great question. Until just a few years ago, we thought that mesenchymal stem cells were all the same, no matter what tissue they derived from. That’s because scientists had categorized them mainly in the basis of surface markers (which are ambiguous at best), not on the basis of any functional characteristic, or where they live in the body. Recently the whole concept of stem cell niches has come to the foreground. When we move past definitions based on markers to those based on what they do and how they behave (including cytokine patterns in culture and in vivo) we get a whole different picture. It turns out that the “native tissue” source of MSC’s defines their physiologic role. Yes, there are molecular differences that can be observed in culture also. Even more so, when you do radiotagging studies to see where the MSC’s that migrate to trouble spots in the body actually come from (hint-not from fat). The issue of how they are better (marrow vs. fat origin) hs several answers. One has to do with differentiation potentials (what cells that have a propensity to become). Another has to do with cytokine secretion patterns, especially in response to stress. There are others. The more we know, the more we realize that these cells are very clever, and very specialized.

      If you are interested in looking more deeply into this topic, there is a good review paper out of the University of Aberdeen, MESENCHYMAL STEM CELLS: A PERSPECTIVE FROM IN VITRO CULTURES TO IN VIVO MIGRATION AND NICHES. Click on thes link for a full text version of the publication. Happy reading!

      vivo.

      • ChicGeek says:

        Thanks for the link! I’ll read that in a sec.

        It’s the cytokine secretion patterns that would make a difference if you’re using the conditioned medium in a topical application, not their differentiation potentials. All the rest is fine and dandy for your body but would make no difference if all you’re using is the cytokines–unless I’m misunderstanding. Also, your use of the phrase “cytokine secretion patterns” makes me think that perhaps the cytokines that the MSCs of different origins secrete are the same but the ratios and concentrations of the various specific cytokines are different? (I’ll be paying attention for that when I read the article.)

        Might be worthwhile to stress the MSCs as much as possible while not compromising their health, if what you’re after is the activation of healing processes… I wonder what would work better–direct stress or figuring out how to synthesize chemical “distress signals”? I’d put my money on #2, but that’s a great deal more challenging technically.

        • drjohn says:

          Differentiation potential in some ways can influence MSC cytokine expression in vitro. If you provide mechanical stress e.g. to MSC’s in 3-dimensional culture, they can respond by wanting to differentiate into chondrocytes (cartilage, bone). The cytokine pattern changes to reflect that destiny. Although certainly cytokine patterns can be changed when remaining undifferentiated is the destiny. But the real point to be made was that MSC’s in different niches are functionally different. Differentiation potential difference is just one way to test that hypothesis. Your assumption that cytokine patterning involves changes in concentration more than appearance of different cytokines is correct. The truth is that all these cytokines are so basic to cell life that they are made almost all the time in almost all cells. It’s the relative concentrations that count.

          Your mention of hormesis (benefits of low level stress signals) really pushes us into the realm of theories of skin aging. A fascinating area. Whole journals are now devoted to the topic as part of cell biology. We know it works well fro muscles, bones. Can we make it work for skin? For the record … I’m putting my money on the same # as you.

          • ChicGeek says:

            Thanks so much for the clarification!

            That research sounds terribly exciting. I’m jealous!

  7. ReggieP says:

    I very much enjoy the in depth science you provide. One question: you make a distinction between stem cells from different niches in the body. What is the best way to choose a product based on this science? Thanks in advance.

    • drjohn says:

      Hi Reggie, there is evidence that conditioned media from different niches of human mesenchymal stem cells contains different concentrations of cytokines. What is more recent is the realization that the MSC’s in these niches are “specialized” in that they perform specific functions. We know that it is the bone marrow derived MSC’s that are the body’s emergency repair team, and that they are the ones that migrate to sites of damage. The cytokines they produce in culture in response to the environment that scientists can manipulate are the right ones for healing stressed and damaged skin.

      What does this mean in terms of product selection? Look for products derived from conditioned media of human mesenchymal stem cells, but then look more closely to see whether these are marrow-derived or adipose-derived stem cells. Choose the marrrow-derived ones. If they mention cytokines make sure there are hundreds of types, not one or two (and certainly not EGF on it’s own). They should mention cytokines – these are the actual active ingredients – the stem cells are just a farm in the laboratory, although a very clever one. Look to see whether the products have been through a clinical trial, preferably with 30 or more subjects. Be cautious about purchasing from dubious sources (you can usually tell from the quality of the web sites) and stay away from those with no science or junk science. If you have questions about a particular product,. let us know.

  8. shimana says:

    I had the opportunity to visit a very nice luxury spa recently. They wanted me to try something called SCM Forte and said it was a stem cell product, but from umbilical cords? Can you comment? Would you recommend?

    • drjohn says:

      Hi Shimana. This is one of those products that try to deceive you into thinking they have tapped into stem cell biotechnology. They haven’t. The active ingredient is powdered ground up sheep placentas and umbilical cords. Every time one of the flock gives birth, the afterbirth is thrown into a barrel. Later a collection of them are chopped, dissolved, and “lypohilized” (powdered). The try to tie it to stem cells by then presenting literature that talks about stem cells in placentas. Yeah, true. But there are stem cells in hamburger too. They don’t isolate them, expand them in culture, etc. They just assume they are there. Bu these low concentrations have no greater benefit than hamburger. Probably they have denatured the cytokines anyway in the processing, so fresh raw hamburger has a slight advantage. I don’t recommend either one. Dr.John.

  9. Bernhard says:

    Thanks for setting up this website. It is quite informative for this new area of skincare.

    I did try the raw hamburger – but I guess that is not the way to go. However this reminds me of an old debate with regard to the origins of growth factors and Cytokines. I saw in another post that you referred to products such as TNS and to products with a large number of Cytokines. There was a debate some years ago with regard to human derived ingredients e.g. taking human body parts from hospitals etc. to isoliate the “cocktail mixture” of cytokines. Do you know if this is still being done?

    • drjohn says:

      To be honest, I had never heard of human body parts being taken from hospitals in order to isolate cytokines. Sounds like a good plot for a Robin Cook novel. I suppose its theoretically possible, but not very practical. The cells have to be alive when captured, so only fresh organs will do. Stem cells are not all that abundant in most organs. Also, since they can be isolated from biopsies of tissues that easily regenerate on their own, why bother? Or get them from “discarded” organs like placentas, and the products of liposuction (functional niche issues aside). So even if the scheme worked, it seems like an inferior business model in addition to being a whacky idea and one that is ethically undefensible. Mind you, some people in the beauty trade seem to be attracted to whacky and morally suspect business practices.

      In a future post we will talk about taking fully differentiated human skin cells (very easy to get) and programming them in 3 easy steps back to being stem cells. Then growing them in culture. Opens up some new possibilities.

  10. lucy lee says:

    Which cytokines are the most important for skin rejuvenation? Are cytokines and matrikines the same thing? I really enjoy your blog. Thanks and look forward to more.

    • drjohn says:

      Matrikines are related to cytokines. They are peptides derived by protein hydrolysis of extracellular matrix (the stuff made by fibroblasts, including collagen, that ends up between dermal cells). They are chemically and functionally similar to certain cytokines. But their action is weaker than the pure (parent) cytokine. There is also evidence that some matrikines are inducers of cytokines. Some are quite good at stimulating fibroblasts.

      For skin the most important cytokines (actually families of cytokines, each with multiple members) are epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. We will soon publish a document showing each key cytokine and it’s function, and where it ties into skin cell growth, metabolism, and it’s role in rejuvenation.

      Remember, these biochemicals are like instruments in a well rehearsed orchestra. You don’t want to listen to a symphony with only the oboe present. The notes should be played by each instrument in just the right order, the right key, the right tempo, etc., to work. Otherwise you end up with “skin cacophony”.

  11. marianne says:

    excellent website. You may have reviewed this product already. What do you think about the” Jeunesse cellular rejuvenation serum.”? Went to a “info Pitch seminar”. need to research a little more. I did see that the first ingredient is stem cells.

    • drjohn says:

      Hi Marianne. Jeunesse may actually be a legitimate product, but because it is buried within a rather insidious multilevel marketing scheme, it is difficult to really be certain what they are selling. MLM is notoriously deceptive, and I personally tend not to believe anything they say. In fact there are obvious twists of the truth all over their (many) sites. They have all the usual earmarks of smarmy salespeople. The founders are serial MLM’ers. Their pictures show them to be an obese couple dripping with gold jewelry. Not sure why their PR firm doesn’t strive for a better image. Notice all the phony “reviews” online, pretending to rate the product, then enticing you to join them (that is under them in the pyramid). They have a doctor fronting for it (Newman) with the claim he invented this stuff (he didn’t – that much I can guarantee. We will get into the history of all this at a later date). Another page calls it a “stem cell lift serum” which is inherently deceptive (it is not a lift, nor does it accomplish anything like a face lift). This kind of deceptive word play calls their marketing ethics into question. There are plenty of additional examples of marketing excess easily found in researching this company. I would suggest that before anyone considers becoming a part of an MLM, or even buying a product from one, that they check out MLM Watch (click on the link). While most of the information there comes from the supplement industry, we are increasingly seeing the same tactics applied to the cosmetics world. The Jeunesse people hawk supplements as well. They have been widely criticized for their past MLM ventures. The product appears to contain conditioned medium from adipose stem cell cultures as an active. You can see from our review here, for reasons we detail, that we consider adipose tissue MSC’s to be inferior to marrow derived cells. These are likely based on the technology based in South Korea, as scientists there favor adipose (fat) tissues. If that is so, they are probably producing it there. I could find only one report of a clinical trial using this product. It only had 18 subjects (too small). The results: “Overall, an average 50% of the participants saw mild improvement, 30% observed significant improvement, and 20% experienced little to no improvement to skin after 90 days use…” I found to be not all that compelling. Mild improvements are easily had by moisturizers alone. So only ~6 of the 18 saw significant improvement. Of course, the marketing literature suggests something closer to a miracle cure. Again, that layer of deceptive marketing masks whatever benefit the product may confer. I suggest you stay away.

  12. kiley says:

    Greetings from the UK. I am fascinated by the stem cell science and the promise it holds for real anti-aging products. I hard that there is disagreement about whether there are actually stem cells in the skin itself, or only in hair follicles. Your thoughts?

  13. susan says:

    Thanks for the great site. Hope to see more about your own work soon.

  14. marianne says:

    Thank You for your reply. I feel the same about MLM. One other question,what do you think of the “Algenist” line?
    in particular the Reconstructing serum with alguronic acid. Saw some good reviews on sephora.com website.
    Thanks again for your great website!

    • drjohn says:

      Hi marianne. This product troubles me a lot for multiple reasons. The whole premise that because algae have to live in harsh environments, then the polysaccharides they make to encapsulate themselves must be good for human skin, is specious at best. Single celled organisms do not have anything resembling human skin. Their cells are more like plants — thick walled. Skin is a whole lot different. It is a whole organ, highly specialized, in a very complex organism. The whole analogy is, in fact, ridiculous to a scientist. Which makes me think that the marketers are in charge here, and they think you are easily fooled with any old yarn they care to spin. They have several studies they tout, all very scientific looking, with graphs. In fact they are so compelling they should be published in the peer-reviewed science journal. Well, they are not to be found in any journal. In fact, the whole scientific world knows nothing about “alguronic acid” (the active ingredient) because there is no such thing. Try searching for it in pubmed. It’s not in the science literature because they made the name up. It’s basically some polysaccharides or alginates (there are thousands of them). Alginates are used as emulsifiers, thickeners, and binders in food production. Algae (seaweed in simple terms) is used as a fertilizer. You know, if you make a name up, it generally is because you are trying to hide something (e.g. from real scientists). Were these studies done in a university-affiliated lab? No some small private commercial venture. Were they ever replicated elsewhere? No. Can they be relied upon as valid evidence? Absolutely not. These types of studies are notoriously difficult to perform, and even more difficult to interpret by real scientists. For instance, they claim “increased cell turnover”. So what does that mean. In a cultured skin model, you can throw lots a of different in and get cells to grow more quickly. E.g. mitogens. But so what? The fastest growing skin is when it turns cancerious. Fast growth does not equal anti-aging. It is far more complicated than that. Their experiments don’t actually address the types of issues that real anti-aging scientists might look for. Plus, if these guys couldn’t get something published given their “amazing” results, then they are then truly the keystone cops of cell science. Another thing– these polysaccharides are huge molecules. How they could possibly be absorbed into real human skin is beyond me (they did their test on skin models, not skin on actual people, like a simple biopsy). Of course large molecules can trap water, which means this product might be a good moisturizer. But there are already thousands of other molecules that fit that description in common use in cosmetics. Here is something chew on: “In our clinical study, the Algenist Concentrated Serum delivered incredible results in just 10 days, decreasing the appearance of the size and number of deep wrinkles by 28% and 25%, respectively”. Now you and I know that wrinkles are deep dermal architectural disturbances of collagen fibers. They take time to impact with any therapy. The only thing that can happen in 10 days is better hydration, which masks superficial wrinkles via plumping of skin. By the way, the first two ingredients in this product are water and dimethicone (like silicone). Algae polysaccharides are way down the ingredients list. So even the moisturizing effect could be from many other ingredients in the product. Finally, their marketing department of this wants me to believe in the story of an accidental discovery by a biofuel company (the same algae as energy source). I am more inclined to think this was some guys brilliant idea to sell what is basically a waste product of biofuels technology. Pretty clever … I can hear them laughing all the way to the bank. I wonder what they say at their company parties? Something like “those suckers will buy anything if we make up some cute story to go with it”?

  15. marianne says:

    Drjohn, Thank you for your quick reply. Your site is saving me money! I did get a sample of the Algenist serum, and I
    do see it as a good moisturizer,(pricey though, $95) leaves a good glow, (not greasy) for a while. I think that is why a lot of women posted good results on website (unless they are all in cahoots with the company!) I’ll stick to my dermatologist prescribed, Finacea and HQ/retinoic acid for my prone to red, and hyperpigmented skin for now. Thanks again for the detailed info!

    • drjohn says:

      Marianne, let’s get Dr George to chime jn here — he has personal experience with stem cytokines for rosacea.

  16. Beautybee says:

    Hi, I love you website. Can you tell me what you think about the lifeline
    skin care products.

    • drjohn says:

      The lifeline skin care products are created by a company called “international stem cell corporation” (ISCO) which has been around a long time. I believe they have burned through a lot of investor money, and never made any, until they decided skin care was good biz to be in. One of those pink sheet (penny) stocks that I find e-mails about in my spam folder.

      First let me say this this is clearly a science-based organization. Not one of the “make believe” science companies that seem to proliferate. They have real M.D.’s, and PhD’s. Their science makes logical sense, fits know scientific constructs. They have published 4 papers in scientific journals. However, none of them have anything to do with skin applications. But their stem cell work is legitimate, and they have a lot of credibility with me to start.

      But when I start to try to answer the question of do their products work (or should they work, based on a cohesive scientific hypothesis with some evidence to back it up), I become instantly frustrated. Their web site is very poorly organized. I cannot find any evidence from clinical trials, and I really did look hard. I find lots of talk about basic stem cell science, but then no specifics about how they apply it to skin rejuvenation. I cannot even find an ingredients list on the site. Reading between the lines on their blog page, I am led to assume that they are growing these cells in culture and extracting conditioned media. It says they “patented a process to extract various bioactive growth factors, peptides and enzymes from these PSC”. However, a quick search of the patent database shows 4 patents granted or applied, none dealing with such a process. But let’s assume they did so, and that is how they derive an active ingredient. I would then want to know which proteins or cytokines, or enzymes, and why these would be helpful.

      Remember Amatokin? This is the company that originally gave stem cells dermatologic products a bad reputation by claiming a secret stem cell ingredient and then sold it like snake oil, with tales of high security facility somewhere in Russia, surrounded by barbed wire. BTW I always assumed the facility might be real, but probably a prison, with some not yet reformed bunco artists as marketers of nonsense. Amatokin is still sold, still pretending to have something to do with stem cells. But look at the ingredients — not a stem cell, cytokine, or any such thing in sight. No actual stem cells used in the making of this product. The labeling no longer claims stem cell derivatives but now instead says “stimulates your own stem cells”. Right. Proof please? Anyway, in another part of their blog these guys give a flattering nod to Amatokin. And they do so without snickering or at least winking. Very strange. Can they not tell the difference? What’s the story there? Are there some ex-Amatokin parolees on the marketing staff?

      I have another issue. They claim that their recently released products are “the first human stem cell products” to reach the market. Not true by a mile. I released a product three years ago, and I certainly wasn’t the first. More marketing hype.

      OK. So let’s just say they are not very discerning, but still clever scientists, who just need some help with their market research and web site to make their own science message a bit clearer. And to perhaps distance themselves the “behind barbed wire” guys. So what about the science they do talk about on their web site?

      They use a type of stem cell called “parthenogenetic stem cells”. They call them non-embryonic, as they are not fertilized by sperm, but instead are induced to become embryo-like using lab procedures. The National Institutes of Health, and other US science agencies consider them to be true embryos. I am not going to decide for you whether this is or is not an embryo, with all the ethical issues that brings up. What I am going to say instead is that I believe the whole concept of parthenogenetic stem cells is stale in the current fast moving world of stem cell biology. It is predicated on the notion that it is better for a stem cell to be more pluripotent than the average (let’s say mesenchymal) stem cell. That notion had its day, but in the world of anti-aging science, and skin rejuvenation in particular, it has long been surpassed. It turns out that cells, including stem cells, can be induced to de-differentiate (get stemier, or more embryo-like). These days, in the lab, you can take a skin cell and make a stem cell out of it. Move it backward on the scale that goes from pluripotent (can become any kind of cell) to committed (differentiated) cell. When humans first did this (just a couple years ago) they thought they were inventing something new. Turns out they were just discovering something that our bodies already do. Cells that have been commiotted (e.g. epithelial skin cells) can be coaxed back into mesenchymal cells from which they derived (epithelial-mesenchymal transition). In fact, there are stem cells that snuggle up to damaged cells and induce them to de-differentiate naturally (see our post). We have long since figured out that differentiation is a two way street. As a result of these discoveries, the whole parthenogenetic thing just doesn’t make much sense in the brave new world of stem cell biology. Why do we need embryonic stem cells (fertilized or not) to farm cytokines, growth factors, and other skin affecting chemicals? This company presents no clear rationale. And if you thing about it teleologically, you might ask what is the role of an embryo in wound healing? Just because you can differentiate into lots of different cell typoes does not make you an expert in skin healing or rejuvenation. There are other stem cells more suited to the task, because their physiologic function is to repair damage. They present no arguments anywhere that there is some rationale as to why parthenogenetic stem cells would benefit skin as a unique organ. Nothing about anti-aging cell biology either. It seems like they have invested many millions in the idea of parthenogenetic stem cells, and decided cosmeceuticals was a market they wanted to be in, as they don’t seem to have much else in the near term pipeline.

      They also make some science gaffes like “Only parthenogenetic and embryonic stem cells possess enough telomerase to make them effectively immortal.” Well, that is simply not true. Every human cell possesses the telomerase gene. Some organs (including skin) express telomerase (make it in the cell). Cancer cells of all sorts make a lot, and they can be immortal (e.g. HeLa cells).

      So, bottom line, I have no idea whether the products work, because they haven’t provided on their web page (or in a journal article) a clear rationale that would allow one to judge the soundness of the translational (how it’s used) science, nor foundational evidence (data) showing that it works. The background science is interesting, yes. But what does it have to do with skin care, and anti-aging? They don’t clearly say, and I cannot guess. If someone can provide more information , I would be happy to revisit this topic. I really want this product to work!

  17. Shana K. says:

    Great website ! I have been buying and reading about stem cells and growth factors products for almost 2 years. I agree with you on everything and all the hype and marketing Bull. 98% of the companies who claim stem cells based products are scam and selling snake oil. the remaining 2% are not their yet and are hoping for a miracle to happen. Stem cells hold much hope but we are not there yet. Stem cells need growth factors and cytokines to grow on a dish, yet they also produce growth factors and cytokines (confusing). Is there a proof that stem cells can produce growth factors like EGF, TGF-B, PDGF ect? can you give me a link of a published paper(s).
    I bought Reluma from TIA and I can’t tell you how disappointed I am with it and Marta. Many readers of TIA have reached out to Marta and asked her to stop the Reluma hype and she deleted every post of them. I sent her an email with proof and legal papers against Invitrx (Reluma makers) and she simply replied with stop using it and see your doctor. I know she’s running a business but come on, people are getting hurt. I also tried stemfactor by Osmosis and got the same reaction on my skin (red rash and itching). Of course after 20 phone calls and emails, I found out that they get their contaminated media from Invitrx. They promised to investigate the matter but so far no answer from them.
    Dr. John this what I’ve did, I went to Invitrx website and looked up the CEO and founder Habib Torfi on pubmed to see his scientific work, not 1 publish work with his name on it. I did the same with CEO of Osmosis Dr. Ben Johnson, again, not 1 published work. My question, how can someone be involved in stem cell research and science and not have published anything?
    So now before I buy anything I run a search on the people behind the product and judge based on their scientific work.
    Keep the good work Dr.J and thank you.

    • drjohn says:

      To be fair, there is a long cycle from research to reporting to submitting for publication to review and to (finally) publication. And if your work involves patents, you have to get all that done first. I am going to do a new series on the latest fiundings for mesenchymal stem cells, and how it relates to skin, starting this week; I believe it will answer your questions about the various cytokines and growth factors. I will provide lots of links back to the original literature so you can go even deeper.

  18. Habib Torfi says:

    Dear Shana K.

    This Habib Torfi CEO of Invitrx. I believe we have a good product and I will be more then happy to refund your money. I apologies in advance if our product did not meet your expectations.

    My best,

  19. ro says:

    My dermatologist recommends TNS in AM after exfoliation, followed with vitamin c and a good sunscreen. Then evening (preferrably 9:30 PM) cleansing followed with TNS and a good retinol. What do you think about this for adding some collegen back into my 50 year old, good skinned face? Thank you.

  20. Surya says:

    Dear John

    The Article is beautifully drafted and it is enthralling. I have few queries , In Some countries like in India , where the Cosmetics guidelines clearly states that there should not be Cells or Tissues or Products of Human Origin in the cream / Anti- Ageing Serum, How can we justify that the Cytokines which are released from the Mesenchymal stem cells in the culture flasks are not from the Human Origin ?. Is there Any Tests available to prove the PRESENCE OF HUMAN ORIGIN in the Anti- Ageing Serum / cream which is been made ?

    According to Me, The cytokines which are released from the MSc’s are only to be considered as Human Origin ,even-though they are released by the MSc’s which are cultured / derived from Adipose tissue or Umbilical Cord tissue – Wharton Jelly and many other sources from the Human Body.

    How can we justify this products made using the Conditioned Media containing Cytokines which are of Human origin in the Market once the cream is aviable for the sale ?

    • drjohn says:

      Surya,

      Products that are of human origin are of regulatory concern in that they could contain bacteria, viruses, etc, or may cause a tissue compatibility problem (which is why blood transfusions must be typed and cross matched). In the case of stem cell cytokines, the cells that make them are of human origin, but the cytokines themselves are processed so that there are no cells, and certainly no infectious particles, in the final product. Now some regulatory authorities recognize the difference and do not restrict human cell derived pure products when applied to skin (our own US FDA included). However, authorities in other countries are not always as enlightened. What some have done in that instance is to take human DNA, transfect it into bacterial or fungal cells using a bacterial virus called a vector (e. coli being the most commonly used) then grow those bugs in large vats where they express high amounts of a single cytokine. Purify it and you have the same exact cytokine as from cultured media, but only one at a time. So, is it safer to extract/purify from cultures of human stem cells or from e. coli and fungi? Really, both are safe. There has never been a reported infectious side effect from a product using human cell cultures. We have been doing it for decades in this country – witness the flagship product of SkinMedica (now owned by Allergan) – TNS serums & creams – which contain conditioned medium of human fibroblasts. Millions of people have been thus exposed without a single adverse effect attributable to its human origins. Not sure about India, but I know there have been recent attempts in some countries where anything of human origin is banned to get authorities to adopt the US FDA’s stance.

      Philosophically there is of course great irony in that there is a tendency to think of human origin chemicals as not natural, but in fact they are as natural as you can get to us humans. Not a foreign substance, one we already make, we just may need more of it. For many years in medicine we treated diabetics with insulin derived from pigs. A good number of them developed allergies or resistance to porcine insulin. Then we figured out how to make human insulin in bug cultures. Now finally we are discovering ways of taking human pancreatic islets and transplanting them into diabetics without causing immune reactions. And next? Transplantations of mesenchymal stem cells (which are remarkable in causing no or little immune response) which have been trained to produce insulin on demand. Very cool.

      I digreess. Hope we answered your question.

  21. Caroline says:

    Dear Doctor,
    Thank you for the wonderful insight sans the hype. I was wondering whether you would consider MSCs derived from cord as superior to bone marrow?

    • drjohn says:

      Really good question. The answer is not certain. There are several advantages of cord matrix derived stem cells when we talk about cellular therapies. But if we focus only on stem cells as ex vivo (in the lab) factories for cytokines good for skin, bone marrow derived stem cells from healthy young adults may still have the advantage. Remember, stem cells have niches which determine their specialities. Umbilical cords are specialized for gestational growth & development. BM-MSC’s are specialized for repair & regeneration. These two things have much in common, but are not the same, from a stem cell biology viewpoint. Here is one example: unlike BM MSC’s, UCM-MSC’s (cord matrix) are unable to prevent activation of B cells from MNC cultures exposed to a known immune stimulus. This is an important immune suppressive (anti-inflammatory) function of MSC’s. We can make logical sense of that in terms of stem cell specialization, as this capability might prove deleterious rather than beneficial for a mature fetus. But if you now take those cord stem cells to the lab and grow them, they will express a different cocktail of cytokines than will cells from young adults (harvested from bone marrow). Is that an important difference? Depends on what you are using those cytokines to accomplish. Given what we know now, it makes more sense to harness the power of bone marrow MSCs than to dip into the cord blood bank for dermatologic applications.

  22. Shana K. says:

    Dear Habib Torfi,
    thank you for the offer, however, i tried to call your company and got no answer. Since I live in Huntington beach, i decided to stop by your company in Irvine on theory st. and drop it myself. While there, I found an XXXXX notice by the XXXXX on your company’s door. I can’t post pictures here but i have a picture of the XXXXXXX on my phone. I can’t say I was surprised, but with little asking around in the building I learned that Invitrx has not been XXXXXX and all the claims of science and patents on your videos are XXXXX. Any company, business or clinic/doctor that deals with invitrx should be approached with extreme cautious. I know Osmosis and Ben Johnson continue to work with invitrx and Mr habib torfi.

    • drjohn says:

      Shana follows up on a discussion she was having here with Mr. Torfi about two years ago. Seems like she has done some investigations on her own. We don’t have the resources to confirm any facts presented, and don’t want to spread any rumors, so we edited a few things. The opinions are Shana’s alone, and she has a right to express them. Shana, we would like to see the photos you took. Please send to docs@barefeacedtruth.com.

  23. Scott says:

    I have some really bad scaring and found this product https://www.procelltherapies.com/product/procell-ampm-serum/ that says it use’s bone marrow mesenchymal stem cell culture.

    Do you think it would help my scaring and it’s worth giving a try?

    • drjohn says:

      Scott, we have seen excellent results form the combination of microneedling and stem cell derived growth factors and cytokines for acne scarring. You should find someone in your area who does these treatments. They probably list them on the ProCell site you mentioned, or you can contact them for referrals. The serum you mention is for daily use between and after microneedling. There is a highly concentrated product used during the actual microneedling therapy.

  24. James Ashley Shea says:

    By accident I found surecell.com today. Their clinic is in the town where I live, Pattaya. All I knew about stem cells was that redneck Christians don’t approve of stem cells from fetuses. Briefly, can my own stem cells be used to rejuvenate my sagging neck with no downside? What about the bags under my eyes?

    Can they zap my sore toe where I stubbed it last week? It’s slow to heal.

    I’m a healthy 81-year-old man, 5 ft. 10 in., 148 lb., excellent blood pressure.

    Jim Shea

    • drjohn says:

      Hi Jim, we actually support some clinics in Thailand that do good stem cell clinical work. Good news is that we now know that adult stem cells work just as well as fetal stem cells for most applications, and have fewer risks. Sagging necks and bags under eyes is easy enough – usually topical stem cell cytokines & growth factors along with physical modalities like microneedling or laser. I would wait on that stubbed toe – they sometimes do take longer than we think they should. Dr George and I will be doing some Asia lecture tours this year – watch this page for info. Tell those folks at surecell to give us a call. We do have some clinics in Thailand that use our products, but the more the merrier.

  25. Jill says:

    Hi there. Recently was introduced to jeunesse global. I’m immediately wary of the product because it’s an mlm. Their luminesce serum has adipose derived stem cell conditioned media. Have you heard of these products and what are your thoughts? Have heard good things….?

    • drjohn says:

      There is a lot to NOT like about Jeunesse. Where do I start? This reflects our scientific opinion on some of the ingredients in the products, and about the ridiculous marketing claims. We have not tested the product in our own lab at this point in time.

      Luminesce by Jeunesse is a product based on human adipose tissue derived stem cell conditioned media. The company claims it is “organic”. What??? Which means that they don’t understand “organic” or the science of their own product. Or they don’t care, and just choose to deceive.

      Fat, from older humans, grown in culture. Human derived. “Organic” by definition would mean never exposed to antibiotics or hormones. That rules out quite a few humans. Are they raised on controlled organic feed lots like cattle? Of course not. The cells are obtained as a byproduct of liposuction.

      Another ingredient in their product line – argireline – so-called topical botox – isn’t what it purports to be. Peptides purported to block the action of the muscles of the face to reduce wrinkles, “just like Botox”. Ah, but unlike Botox, where clinicians must be trained to know exactly where and how deep to perform the injections (to prevent unwanted side effects) there is no such training for these topicals making wild claims about blocking the neuromuscular junction. Here is the logic you need to consider: IF those peptides do what they claim to do, facial muscles would become weakened or paralyzed. Your facial expressions would change. Your eyelids would no longer open or close fully, resulting in ptosis. IF they did that, they would be affecting muscle, not skin, and would immediately be labelled drugs by the FDA, just as Botox is. Because they cannot even penetrate into the muscular layer of the skin. In short, they don’t work as advertised, which, if you think about it, is a good thing. In fact, even Botox applied topically does nothing. You have to inject it to get it to the neuromuscular junction.

      But unlike Botox, where clinicians must be trained to know exactly where and how deep to perform the injections (to prevent unwanted side effects) there is no such training for these topicals making wild claims about blocking the neuromuscular junction. Here is the logic you need to consider: Because they cannot even penetrate into the muscular layer of the skin. In short, they don’t work as advertised, which, if you think about it, is a good thing. Our opinion of any product that contains these ingredients is that they are whacky from the get go.

      We have written extensively about the use of adipose-derived (fat) stem cells in skin care. The main things to know are:

      1. The cytokine profile of fat stem cells is likely to be inflammatory, because fat stem cells secrete adipokines in abundance, which are inflammatory, and fat stem cells donors are significantly older and more likely to be significantly overweight or obese (an inflammatory state).

      1. Chronic inflammation has consequences, including: a predisposing factor for many diseases fibrotic rather than scar-free healing (TGFβ-1, TGFβ-2 overwhelming TGFβ-3), pro-aging rather than anti-aging

      A model of regeneration deriving from knowledge about phases of wound healing dictates that positive results will come from a balance of cytokines with a predominance of anti-inflammatory cytokines, if they are to achieve anti-aging benefit.

      More on fat stem cells: http://barefacedtruth.com/2012/07/04/cytokine-stem-cell-tissue-of-origin-issues-part-4-an-inflammatory-view/

      Then they claim one of the proponents, a Dr. Giampapa, was nominated for a Nobel Prize in stem cell research. Oh, really? Anyone can be nominated for a Nobel prize by the way. I know he didn’t receive any actual awards – those are announced by the Committee. Plus, the Nobel committee makes all recommendations for all prizes a highly secret matter – and doesn’t release that information until 50 years later! So who released this info? Of course, it cannot be proven since it is a secret.

      Did somebody actually break the longstanding rules? Who is the reliable source of this information? Show me something official, e.g. from the Nobel Committee. Can you? Or are you blowing smoke on us all? This is no reflection on Dr. Giampapa who I hope is merely the an innocent victim of a hoax. No self-respecting scientist would make an unprovable “nomination” claim about himself. Especially if he ever hoped to win an actual prize.

      Just because I could, I went ahead and nominated myself for a Nobel prize. That makes it official (or at least as official as any other “nominee” announced in the past 50 years – during the period of required absolute silence, per the committee’s longstanding rules). I put it in my Linked In profile which according to some Jeunesse folks is as good as carving it into stone. All I need to do now is send out some phony press releases. Now will Jeunesse pay me as a spokesperson?

      DrJohn (Nobel Prize 2015 Nominee)

  26. Donna says:

    This website just saved me a LOT of money. I’m so glad I found it. I’m also very glad, as I now have the potential to be another Nobel Prize nominee for 2015!! What a prestigious thing I can do for myself!!
    Thank you so much for revealing the truth about so many of these products and their claims. Gotta love science. 🙂

  27. Evangeline says:

    I am with Jeunesse and everyone is going crazy over the Instantly Ageless. It is very difficult to sell these products for me. I can sell sachets of the Instantly Ageless all day long but I cannot sell the rest of the skincare. I have wasted a lot of money on Jeunesse. I have also heard that the Instantly Ageless has cancer causing ingredients. Is this true?

    • drjohn says:

      I don’t think Jeunesse causes cancer. I do think it is poorly formulated, overhyped, and underwhelming in terms of results. Of course, now that we are both “Nobel nominated” I may have to cut it some slack. NOT!

  28. alex says:

    So after reading these posts, are there actually any anti-aging skin care creams on the market that contain stem cells that actually work and give the results that consumers would believe they are going to get ??
    For example, are there skin care creams that give the quite obvious changes to skin tone, texture, colour etc. or are they really no different to the many other lines of skin care products that are on the market?
    I ask this question because of the comments of the lack of effects derived from stem cells not of the origin tissue, and those derived from fat. It would appear that only way to actually get an real benefit would to have one’s own stem cells harvested, then put in to a topical cream / serum and then apply. Am I correct in this ? or are there creams out there on the market that do actually perform ?

    • drjohn says:

      These products do not contain stem cells per se, but rather a collection of native human molecules – cytokines and growth factors. They can be quite effective. In fact, in the world of aesthetic dermatology and plastic surgery, they currently are viewed as the “top of the pyramid” in terms of anti-aging bang for the buck. Much more physiologically rational compared to other classes of skin care product. For examples of these types of products visit this review site . You will see documented evidence of performance there.

      There is now even more accumulated scientific evidence that bone marrow is the stem cell of choice for deriving growth factors and cytokines. Fat stem cells confer all sorts of problems. We will detail the latest evidence in a new BFT post soon. Please stay tuned.

  29. Jo says:

    I am so glad to have found your informative site. I am one of the many people around the globe who have allowed themselves to be suckered in with the anti ageing hype. I became involved with Jeunesse three months ago. I immediately had concerns regarding the products containing the Ta65 ingredient given there is conflicting information concerning it’s safety and I could not find details of independent trials. I have however been using and promoting the skin care range until now! I have spent some time trying to understand the ingredient list of their Serum. The product packaging makes no mention of the adipose derived media, however this is clearly shown on the ingredient list on their website and also in their videos. I am concerned that this product does not contain the stem cell byproduct. It has also made my skin worse in my opinion.

    • drjohn says:

      LUMINESCE™ cellular rejuvenation serum has adipose tissue derived conditioned medium as its first listed ingredient. We have major concerns about the continuous daily application of this material to facial skin. Unlike bone marrow derived stem cell media, that coming from fat contains a class of chemicals named adipokines (e.g. leptin) which are known to be inflammatory. There are a number of recent scientific publications that suggest a link between these and certain cancers. The docs at BFT have become increasingly concerned and have begun to present this data at professional academic conferences. As you might expect, we have come under attack by companies purveying such products, in the U.S. and internationally. We have just become aware of a major disinformation campaign on the part of one such company, and we now feel compelled to tell that whole story of intrigue and deception. More on all this in a series of posts to begin in the next few days.

  30. Diane says:

    This is all new information for me and very enlightening! I have been using Jeunesse’s serum for a month now and just received my second bottle. At 85$ a bottle it is much more affordable than AnteAge, however after reading all this information I am seriously considering trying AnteAge. I am wondering if there are any contraindications to using AnteAge with microneedling on more than just the face and neck? I have very wrinkled saggy skin on my arms and starting on legs now too. I would like to do microneedling on face, neck, arms and legs (maybe even stomach) and then apply serum. Would there be a danger in applying so much serum on body? And finally, how often would you recommend microneedling? I have a 1.5 mm and .5mm roller. (side note: I have been microneedling for over a year now sometimes once a week with no visible improvements, I am hoping with a good serum I might get some improvement). Thank you very much for your time and efforts.

  31. Diane says:

    I am interested in using Anteage and microneedling but wondering if there is concern with applying such a stem cell serum on more than face? I just turned 50 and have very wrinkled saggy skin all over body. It seemed to happen so fast. I am feeling embarassed to wear tshirts and shorts! I’ve tried many things with no success. Microneedling has done nothing or maybe even worse. I wonder if using such a serum with microneedling on arms, legs, neck and face would be safe, beneficial? Thank you for your time and efforts.

    • drjohn says:

      Diane – you can bathe in it, although that might be cost prohibitive to fill a bath tub. I’m wondering whether you have a skin laxity problem related to something else other than simply aging. I would recommend getting an evaluation by a dermatologist familiar with such things. What city do you live in?

  32. Missy says:

    Dr John, re yr 25 September 2015 post re Juenesse, I looked this week and did not see any mention of adipose SC derived medium in the Ingredient section on the Juenesse global website for their serum and moisturiser and other products. I also saw on a distributors website (which they give to signer ons, to spread wild claims) that he gets lots of returns from older women because the skin care range makes their skin go red. Possibly due to inflammatory response you have mentioned?

    • drjohn says:

      That would not surprise us in the least.

    • drjohn says:

      You are right! Go to the web site and choose different countries – you get different ingredients BUT EXACTLY THE SAME SET OF CLAIMS AND MARKETING SPIEL. So probably Australia told them they couldn’t sell it with Adipose Derived Adult Stem Cell Conditioned Media, so they just stripped it out and put in BUFFERED SALINE!!!!! Folks, that’s slightly salted water!

      Wow! This has got to be the most deceptive bit of market manipulation I have ever seen. Take out the active ingredient, substitute water, but it still work just as well?

      I smell a lawsuit brewing over there in Oz. I promise to testify!

      Here is the stark evidence cut and pasted:

      USA (and most other places)- ingredients- Adipose Derived Adult Stem Cell Conditioned Media, Purified Water, Glycerin, Saccharomyces Lysate Extract, Hydroxyethylcellulose, Gluconolactone (and) Sodium Benzoate, Sodium Hyaluronate, Xanthan Gum, DL-Panthenol, Sodium PCA, Allantoin, Superoxide Dismutase, Sodium Hydroxide.

      Australia ingredients: Phosphate Buffered Saline, Purified Water, Glycerin, Saccharomyces Lysate Extract, Hydroxyethylcellulose, Gluconolactone (and) Sodium Benzoate, Sodium Hyaluronate, Xanthan Gum, DL-Panthenol, Sodium PCA, Allantoin, Superoxide Dismutase, Sodium Hydroxide

  33. Jen says:

    Australia has the TGA akin to FDA, for J to get approval would take many years, so I heard they are not bothering about it. I think that is why they came up with idea that each individual member (customer) gets given website $39, then the customer buys product themselves direct from USA, and TGA allow it as it is “for personal use only”. The upline members details included in purchase so they get their commission. Very sneaky way around the TGA. Doctors here have also used a loophole in TGA re SC cytokines injections – TGA allows in general these sorts of treatments as long as it is derived from patients own body. TGA not happy about and will prob aim to close loophole. So, the Australian product with saline water probably does not exist, and customers aware they are purchasing from USA.. So would be tricky to make strong legal case of false advertising – their products are not stocked in Australia!

    • drjohn says:

      Very tricky indeed. If true, would you want to support a company that deceives so blatantly? Is their product formulation done with equal conscience (or lack thereof)?

  34. Mike Zdanowski says:

    Dr John – Out of curiosity, where do you get your conditioned media? Are there any sources commercially available and is it expensive? Mike

    • drjohn says:

      Mike, it is expensive. Here is why: we manufacture the conditioned media (CM) ourselves, in collaboration with a major university stem cell research center, and specialized off-campus centers (part of the stem cell transplantation community) with expertise in harvesting bone marrow, extracting and isolating stem cells correctly, and expanding them in culture using protocols developed to optimize the MSC secretome for specific indications in the realm of regenerative medicine. We know of no commercial sources of BM-MSC conditioned medium. And if there were – the results would likely be “generic” – i.e. the output of stem cells whose only biologic imperative of the moment is to expand their numbers under whatever culture conditions. They like to occupy space. The paracrine activity of stem cells who are not in “work mode” (other than mere expansion / differentiation) is quite difficult to define on a consistent basis when culture conditions are not highly controlled. And if that is not tuned to a specific desired outcome, the results can reflect the remarkable ability of stem cells to respond to things we are not controlling. Too much variability. Not quite random – but many vagaries that can frustrate the agenda of the stem call “farmer”.

      The proprietary protocols we use are ones developed by us over many years, tuned to epithelial regenerative and immunomodulative goals. We continue to refine. Our stem cell production work is overseen by highly experienced PhD’s who author textbooks on the subject of stem cells. While CM as a topical is regulated as a cosmetic, the manufacturing standards we employ are equivalent to cGMP for biologics. The CM paracrine composition depends on a number of variables that we must control. This means e.g. specialized chemicals, growth media, incubators, etc. The environment is far more complex than that typical for a cosmetic ingredient (ever watch them get made?), but the real incremental cost (and differentiating feature) is the human capital required. Combined efforts of MD’s, PhD’s, etc. This is a very narrow niche of a specialty. Science guys with a master’s degree in cell biology can purchase cells and grow them in commercial growth media. But that is only 10% of the task. You must also understand the unique properties of these special cells as they apply to dermatologic regenerative medicine. Refer to a mound of data collected over years of experimentation. And finally, these cells are from paid human youthful adult volunteers. Not waste products of liposuction (as are adipose stem cells). They are fresh and vigorous. That adds expense. Not immortal cell lines genetically frozen in time. The bone marrow stem cell niche is the body’s natural “mobile” organ for regeneration and repair. Fat stem cells you get for free. Our cells are precious. Thanks for asking!

  35. Victor says:

    Dear Dr. John,

    After reading dozens of studies on stem cells I have to say this article was very informative. Thanks for putting the tame to educate us and share knowledge and science.

    I have a very important doubt about embrionic stem cells vs adipose-derived stem cells. I am about to participate in some clinical study for some persona health condition. One is using ADSC and the other one using ESC. The doctor using ESC states that “The product injected is a placental stem cell product that mixes mesenchymal stem cells with growth factors and cytokines and an extracellular matrix to promote wound healing, angiogenesis, and tissue repair”

    However, the other doctor using ADSC, he states that he uses growth factors (nothing about cytokines).

    Given these differences, which one would you think has better options to help? (The condition is Peyronie’s disease). But more importantly, it looks like cytokines are already secreted the stem cells, so why to collect them, isolated, and inject them along with stem cells? Is it better that approach that doing stem cells alone?

    I have no idea which kind of cytokines the doctor i using, but I can ask. I know you mentioned that is always to have as many different ones as possible.

    Oh, one last thing…are cytokines obtained from ESC any better for repair than the ones obtained from ADSC?

    Thanks for all your work and explanation. It was a bless to find this website.

    • drjohn says:

      Victor, the clinical study you describe is a good one, although the terminology is incorrect (See my comment to your question in the “Do you know that fat stem cells and bone marrow stem cells are really, really different?” thread.). Placental stem cells are not embryonic – technically they are “adult” tissues in the stem cell world although that label can confuse. Placentas are a mixed tissue of both maternal and child origin. Adding other cytokines and growth factors is rational if you suspect that the placental stem cells are not making the ideal mix of these biosignals “out of the box”. My theoretical preference in all this would be the placental stem cells over the adult fat stem cells for reasons discussed above. Both types of MSC’s have been successfully used for Peyronie’s but since fibrosis is the issue I would favor the placental stem cells. I would of course also favor adding TGF-beta3. This is all theory for now – nobody has compared the two in a single study.

  36. Victor says:

    Hi Dr. John,

    You are right in that my terminology was incorrect. Pardon me for my getting confused between embryonic stem cells and placental stem cells. The good thing about my confusion though is that I was able to learnt a lot in your answer in the other thread about them too, so I am now much better informed 🙂

    The study that I refer and that I believe you also know now does in fact talk about placental stem cells. It is good to know that you have a good impression about that specific study. And also good to know about your preference on placental over ADSC for anti-scar, anti-fibrotic purposes. This has helped me in my decision to chose that over the ADSC treatment.

    I have one other complicated question that hopefully you can comment on. For my condition, fibrosis/scar-issue is one problem, but sensitivity loss is the main problem. Some doctors say that scar-tissue can press on nerves (in this case penile dorsal nerve or peripheral ones). Since I have a injury due to stretching (using some of those devices for that purpose), I lost sensitivity and I don’t feel a thing. When I wake up in the morning, I don’t feel anything unless I look.

    The doctor that made the study told me that placental stem cells can help both with fibrosis and also with nerve regeneration. So i guess that my questions would be:

    1) Do you agree with that statement with regards to sensitivity/nerves?
    2) Is there any cytokine or growth-factor that you know off that helps on that matter? I have read in pubmed.org about CGF (Concentrated growth factor) as a complex that comprises a fibrin matrix incorporating growth factors and plasmatic and leukocyte cytokines.

    Thanks again for bringing up knowledge we need.

    • drjohn says:

      Here is the one published paper on the subject I am aware of. It’s an animal study so be cautious in translating to humans. Here is the paper on CGF. Again, this is very early laboratory level experimentation. I think the methods are solid, and the information fits well the knowledge base of what the secretome of mesenchymal stem cells can accomplish. Good science. It will likely be years before controlled clinical studies will appear, so your treatment would definitely be leading edge experimental. Best wishes for you in all this Victor, and please come back and update us on your progress.

  37. Victor says:

    Hi Dr. John,

    Thanks for your words and for the study about neural cells 🙂 I will definitely report back on my progress.

    I have found this one doctor that claims that amniotic stem cells being used are just a scum, because they are frozen and when they are delivered from a doctor to a patient, there are no cells alive: http://www.regenexx.com/amniotic-fluid-stem-cells-pros-and-cons-more-scams/

    On the other hand, in the study my doc published I believe he uses placental stem cells that he buys I believe from here: http://skyebiologics.com/products/surgical-products/cryomatrix. If you read that page, that is exactly what the doctor above claims to be a scum.

    My doctor has published as you know the study about Peyronies (http://www.ncbi.nlm.nih.gov/pubmed/26414724), and he uses exactly that.

    So who am I to believe? I hope you can shed some light on this.

    Thanks a lot.

  38. Kira Miftari says:

    Wow, I just found yr blog and I am blown away! While I will not pretend that I understand everything you write about, I am definitely making some progress;-)) I am curious what do yo think about topical 1) Human Stem Cell Conditioned Media, Human Fibroblast Conditioned Media as in the famous Osmosis Growth Serum, and 2) Growth Factor Technology as in AQ Skincare Solutions? I don’t know where to look for an objective view on the effectiveness of those ingredients when it comes to strictly topical delivery in a form of a skincare serum. Would appreciate if you shared
    http://www.aqskinsolutions.com/products/active-serum
    http://www.osmosisskincare.com/StemFactor.aspx
    THNX IN ADVANCE!

    • drgeorge says:

      Wow, you asked a question about something we are truly devoted to, i.e. human cell culture derived skincare. Stem cells are NOT all alike. We are great fans and experts at working with human bone marrow mesenchymal stem cells because of the command and control role they play in tissue repair and healing throughout the body from birth to death. We are not fans of fat-derived stem cells because of the pro-inflammatory pattern of cytokines and growth factors they produce. Inflammation is not something one want to promote in their skin, especially on a daily basis. The bone marrow stem cells do the opposite – quench the fires of inflammation. Fibroblasts are cultured from both the Osmosis and AQ products, as well as the first generation product in this space, TNS Serum by Skinmedica. Fibroblasts are the “weaklings” of cell that are cultured. They don’t produce much, especially when compared to bone marrow stem cells which produce 15 to 50 times as much, depending of which bio-signal one is assaying.

      Tell you what: I just finished editing a revision of a “white paper” that covers this subject. It will answer a lot of your questions. You will be the neighborhood expert!!! I’ll send it as an attachment to your email.

  39. Maria says:

    Hi,
    My doctors just recommended a product by SkinMedica, TNS Essential Serum. The first listed ingredient is Human Fibroblast Conditioned Media, which frankly sounds terrifying. I haven’t found much info on it. Does that product come from other human skin and can potentially add someone’s DNA, disease or cause cancer? I am hesitant to use and would appreciate your input.

    • drgeorge says:

      No need to be frightened, Maria. There is nothing in TNS Serum that should terrify you, although we are not fans of skin products based on fibroblast conditioned media, but that’s for totally different reasons than the ones you cite.

      First of all, please spend some time reading the posts here on BFT about conditioned media based products and you will find that conditioned media, by definition, is the nutrient broth that remains after all living cells and cell parts are ultra-filtered and discarded. No DNA to be found. As far as disease transmission goes, including cancer, millions and millions of units have been sold and used over the past 15 years of numerous products based on fibroblasts and stem cells from fat, bone marrow, and umbilical cords. BFT is unaware of a single documented case of disease causation or transmission. That doesn’t concern us either.

      Become, however, educated about what the differences are in the bio-signal pattern produced by each type of cell – they are totally different from one another based on the genetic machinery and physiologic role of the cell being cultured. Fibroblasts are VERY weak producers of bio-signals, that’s not their physiologic role. Fat and umbilical cord stem cells produce highly pro-inflammatory patterns. Inflammation has long been recognized as pro-aging in all tissues so we ask why would want to apply products to the skin on a daily basis that promote inflammation? Makes no sense.

      What does make sense is applying products that subdue inflammation. The bio-signal pattern produced by bone marrow mesenchymal stem cell is markedly anti-inflammatory which is why the BFT authors selected it as the source of the cytokines & growth factors in products we produce.

  40. Karen says:

    Hi doctors,

    I’ve read a lot of the reviews here and they are great, I have learned a lot from here. Thank you! May I ask which stem cell skincare brand would you suggest? I’ve tried to search on the internet, and they’ve rated anteAGE with stem cytokines as number 1. I want to know your opinions before I spend any money on expensive skincare.

    • drjohn says:

      We agree with those reviewers and the internet (crowd wisdom). AnteAGE is the very best. We are, of course, a bit biased …. since we invented it and did the clinical trials 🙂

      • Karen says:

        Hi Dr John,

        I have purchased the anteage serum and accelerator and they’ve just arrived. I am so excited! However I just want to know how long is the expiration date? And incase if it’s not suitable for my skin, is there any money back guarantee? And is there any promo code for first time buyers? I forgot to ask before purchase!! Perhaps next time 🙂

        • drgeorge says:

          Karen, all of our products are guaranteed, and you don’t even need to send them back (unless it’s a airless pump failure in which case we want to examine why there is a problem – has only happened a couple times.) If there is a problem, just let us know within 30 days of delivery to you and you will receive a full refund. We can proudly say the number of refunds is still in single digits.

          To understand why we consider the Jeneusse technology inferior to ours, read our blog article on the difference between bone marrow and fat stem cells. That will answer your question.

          We recommend using the products within a year of activating the airless pump.

  41. Where can I purchase anteAGE with stem cytokines for my Med Spa microneedling treatments?

  42. Tahir says:

    Hi Dr,

    I am using Cholley’s plant stem cells like apple, alpine etc for the last 6 months or so and there is no improvement at all on my laugh lines, forehead and under eye fine lines wrinkles and sagging (lose) skin.

    Do you suggest any best result oriented tropical product to overcome my problems?

    Best regards

  43. Barbara M. says:

    Hi. Dr.
    I’m 63, very fair, and started cosmetic rolling with a .3 roller. I’m applying AnteAGE MD serum and Accelerator immediately after but get some burning when Accelerator is applied to my neck and chest after rolling and the neck in particular stays itchy and red for 24 hrs. I’m reluctant to apply sun screen so as not to introduce any non-biological chemicals since the skin is reacting to the Accelerator and doesn’t if I haven’t rolled. Would the Stem BioGel be a better option for my neck? Also, How many hours after rolling with a .75 roller can I start using the BioGel since it’s an adjuvant for medical level needling?

    I’m really liking the AnteAGE products and have just ordered my third set.
    Thank you!
    Barbara

    • drgeorge says:

      Barbara, thank you for using our products but please spend some time reading our posts on microneedling. You will learn that for a period of several hours after treatment, the skin barrier is compromised by the many hundreds of tiny perforations, even when short needles are used. This is a time during which one should be very careful what they apply. We recommend you apply ONLY products that contain substances naturally found within the skin, no foreign substances. That excludes even our Serum and Accelerator which are formulated to provide preventative and restorative benefits to all skin types, all genders, ethnic groups and ages, but which do have substances in them foreign to the skin. So, what should you do? Three years ago we created a microneedling solution based on bone marrow stem cell conditioned media, hyaluronic acid, and in the MD version, additional TGF-beta3. All of these materials are found in your, mine, and every other person’s skin on the planet. They are natural. Several hundred thousand doses have been used without report of a single adverse event. We make our own brand and private label the product for some of the biggest names in the business. They settle inflammation down rapidly and enhance the healing response. We produce a medical, esthetician, and home version. Email back if you want to learn more. (BTW, we consulted with Dr. Lance Setterfield in developing our formulation. Google him; he’s an international guru on the subject and wrote the most complete textbook on the subject.)

      We STRONGLY urge you to stay away from snail based “growth factor” products, and even be careful with Vitamin C serums and hyaluronic acid products. Some of them have ingredients that have caused serious complications for some women, including granulomatous dermatitis, which may be permanent.

  44. LC says:

    Hello! I have been a long time reader of BFT and really enjoy learning from this site and appreciate the time you spend posting information and answers here. It is such a refreshing and surprising change from many of the marketing driven websites out thereby related to anti aging products and topics. I have ordered and just received the Ante Age microneedling vials and look forward to trying it out soon. I am also interested in either the Ante Age MD serums or the ProCell Therapies MD serums but have not been able to find a place to compare their full ingredient lists to each other. Are you able to tell me if they are the same formulations or are there differences in the ingredients and/or concentrations of ingredients between the Ante Age and ProCell serums (both the serum and the accelerator)?
    I do not believe there is a practitioner for either brand of products near me, so wondered if there is a way to try the version? Thank you!!

    • drgeorge says:

      You can’t go wrong with either the AnteAGE/AnteAGE MD or ProCell/ProCell MD products – we make them both, sort of like two brands of corn flakes made in the same factory. Except, of course, these corn flakes are based on the latest and greatest in human stem cell science. Email back if you’d like to learn how to order, or contact ProCell. We love their wonderful team just like we love ours.

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