Unsure about Growth Factor and Cytokine Products for Skin Care & Microneedling? | BareFacedTruth.com

Unsure about Growth Factor and Cytokine Products for Skin Care & Microneedling?

By now, BFT readers are well familiar with our disdain for the hyperbolic and confusing marketing messages constantly foisted upon skincare product consumers. For more than a decade, marketing maestros (charlatans?) tried to hoodwink scientifically unsophisticated women by commandeering the words “stem cell” to sell products having nothing to do with stem cells, or by ginning up the argument that a plant “stem cell” can somehow produce the biologic messenger molecules that will “instruct” human skin cells to change their errant ways. Hopefully, our readers have progressed beyond such semantic innocence and vulnerability. Today we want to go beyond scientific absurdities and address the real world differences between products that actually do contain human cell-derived growth factors and cytokines. The good news is there is abundant scientific documentation that confirms that topically applied human growth factors and cytokines can provide significant benefit to aging skin. Now, with the enhanced penetration and direct access to metabolically active skin cells produced through microneedling, the nature of applied bio-signals becomes even more important, and more potent in producing benefit…or harm. Thankfully, sorting this out is relatively simple since the scientific literature contains abundant instructive data and there is a growing body of supportive clinical evidence.

A Quarter Century of Research and Use The evidence proving benefit of growth factors and cytokines in wound healing dates back to the late 1980’s. A 1987 study examined the role of platelet-derived growth factor in wound healing. In vitro (laboratory benchtop) experiments showed PDGF (platelet derived growth factor) “stimulates DNA synthesis and chemotaxis of fibroblasts and smooth muscle cells and stimulates collagen, glycosaminoglycan, and collagenase production by fibroblasts. These in vitro properties suggest that PDGF, delivered by platelets to the site of injury in vivo, may play an important role in the initiation of the wound repair process.” The study further explained that IGF-1 (insulin-like growth factor 1) and EGF (epidermal growth factor, when combined with PDGF, provided additional synergistic benefit.

This diagram illustrates the negative influences on healing of lack of blood supply, oxygen, growth factors and cytokines on top, and the positive benefits of various important growth factors and cytokines on the bottom. The influences of growth factors and cytokines, however, is actually much more complex as there are dozens in play at any time, all competing for influence. The “net” effect of the overall bio-signal pattern is of paramount importance as is discussed below.

Drgeorge’s first exposure to clinical use of growth factors and cytokines was in the operating room in the early 1990’s when PDGF saturated gauze was packed into chronic non-healing ulcers in diabetic patients with good results. Since that time, platelet derived growth factors and cytokines have found clinical usefulness in bone and joint treatments, and as pro-healing adjuvants to promote tendon and ligament repair. It is thus no surprise that more than a dozen years ago, researchers became interested in documenting the benefits topically applied bio-signals provide to aging and photo-damaged skin. As explained below, the use of platelets to obtain bio-signals for topical application to the skin has  pros and cons.

Early Evidence of Benefit

In the early 2000s, researchers began to explore the potential benefit of topically applied growth factors and cytokines to aging and photo-damaged skin. Some of the initial studies focused on bio-signals produced from cultures of fibroblasts, a reasonable cell type to consider because of its importance in production of collagen, elastin and intracellular matrix within the dermis. While evidence now shows that fibroblasts are not the optimal cell type from which to obtain such bio-signals, this early research set the stage for successful marketing of an entirely new class of topical skincare product.

Reversal of photodamage with topical growth factors: a pilot study. “The application of a mixture of topical growth factors may stimulate the repair of facial photodamage resulting in new collagen formation, epidermal thickening and the clinical appearance of smoother skin with less visible wrinkling.” J Cosmet Laser Ther. 2003 Apr;5(1):25-34.

Efficacy of novel skin cream containing mixture of human growth factors and cytokines for skin rejuvenation. “…significantly reduced periorbital and perioral wrinkles, as well as improved skin texture of the chin after one month of treatment, which confirms the beneficial use of growth factors and cytokines for skin rejuvenation reported in 2 earlier studies.”   J Drugs Dermatol. 2007 Feb;6(2):197-201.

Endogenous growth factors as cosmeceuticals. “Topical application of human growth factors in multiple clinical studies has been shown to reduce the signs and symptoms of skin aging, including statically significant reduction in fine lines and wrinkles and increase in dermal collagen synthesis.” Dermatol Ther. 2007 Sep-Oct;20(5):350-9.

Human growth factor and cytokine skin cream for facial skin rejuvenation as assessed by 3D in vivo optical skin imaging. “Growth factors, in addition to their crucial role in cutaneous wound healing, are also beneficial for skin rejuvenation. Due to their multifunctional activities such as promoting skin cell proliferation and stimulating collagen formation, growth factors may participate in skin rejuvenation at various levels. […] We found that topical application of growth factors and cytokines are beneficial in reducing signs of skin aging.” J Drugs Dermatol. 2007 Oct;6(10):1018-23.

Reduction in facial photodamage by a topical growth factor product. “This study demonstrates that addition of a topical formulation of growth factors and cytokines to a basic skin care regimen reduces the signs of photoaging.”  J Drugs Dermatol. 2008 Sep;7(9):864-71.

Topically applied physiologically balanced growth factors: a new paradigm of skin rejuvenation. “Clinical studies have shown that topical application of products containing high concentrations of a physiologically balanced mixture of GF appears to reverse the signs of skin aging.”   J Drugs Dermatol. 2009 May;8(5 Suppl Skin Rejuenation):4-13.

Healing is like a Symphony Orchestra, not a String Quartet The body contains trillions of cells, divided into over 200 different individual types of cells. Of these, only the red blood cell does not participate in the complex communication system that controls cellular behavior, including growth, regeneration, inflammation, and healing of tissue.

The “words” of communication are growth factors and cytokines (among others). They function by activating cellular membrane receptors that in turn initiate cascades of intracellular biochemical interactions that reach all the way to the nucleus, up-regulating and down-regulating genetic behavior – powerful signals, indeed. Below is a simple schematic of a cell receptor being activated; below that an example of the consequential complex intracellular events of that activation that determine whether a cell divides, differentiates, migrates, or performs any one of a myriad of other possible actions. Growth factors and cytokines make tissue healing, and indeed life itself, possible.

Growth Factors and Cytokines Never Exist in Isolation

There are dozens and dozens of bio-signals in the orchestra of healing; they never exist as single substances.  Because of the complexity of cellular communications, they may have resultant complementary or opposing effects. It  is always the net “pattern” present that determines the physiologic effect. When cells are cultured in the laboratory to harvest growth factors and cytokines as an ingredient for an anti-aging skincare product, or an adjuvant useful for microneedling, the sources of the bio-signals, and particularly the type of cell cultured, is of paramount importance. It determines the type and character of bio-signals produced and their relative concentration. As demonstrated below, these are both important considerations when selecting the optimal source from which bio-signals for anti-aging and microneedling should be obtained.  As a starting point, we need a brief word on inflammation and healing, particularly in the skin.

Inflammation – Not a Good Thing when it comes to Skin Healing

By now, nearly everyone is aware that inflammation is the enemy of good health when it is of the chronic smoldering variety. Inflammation is associated with nearly every disease, malady, or debilitating condition of the elderly. It is also associated with aging of skin and all that comes with it including abnormal pigmentation, redness, wrinkles, fine lines, etc. In darker skin types, inflammation of any sort is notorious in producing abnormal pigment patterns. Aesthetic treatments that cause deliberate tissue damage in order to promote new younger looking skin may have undesirable results (fibrotic healing or abnormal pigmentation) with inflammation as the primary culprit.

inflammation should be considered a good thing except in those cases where mother nature is concerned with destroying pathogens or mopping up damaged or dead tissue – like in the very old days when a cave man was bit by an animal or cut his leg on a rock. Modern hygiene and sterile medical procedures make the inevitable inflammation seen after trauma somewhat unnecessary and potentially counterproductive to producing the most pleasant aesthetic result. For that reason, BFT considers products that are pro-inflammatory, especially when intended for chronic use, less than desirable.

Considerations as to Which Cell Type is Optimal for Culture

In choosing a product for topical skincare or microneedling that contains human derived growth factors and cytokines, there are three principal considerations as to what is the best cellular source for the bio-signals – what is the pattern, and what are the concentrations, of the bio-signals produced by that cell in culture, and how are the growth factors and cytokines being processed. While assays provide precise answers to these questions (and examples will be provided below), good insight can be gleaned by examining the physiologic role each type of cell plays in the body, and the ways in which products are produced from the cells after culture. Brand names are not important for this exercise. BFT will let that be the readers’ homework assignment.

Major Bio-signals of Interest

This chart lists the growth factors and cytokines primarily involved in healing and regeneration of tissues. Of particular note is that nearly all can be categorized according to their impact on inflammation, either acutely or chronically pro-inflammatory, or anti-inflammatory. These distinctions are important when one determines if a growth factor and cytokine “cocktail” in a product is likely to promote inflammation or quench it.

Cytokine Patterns Produced by Cell Cultures differ Dramatically

It is not surprising that cell culture growth factor and cytokine outputs vary dramatically because the cells cultured perform completely different physiologic roles. It is also not surprising to learn that stem cells, in particular, are prolific producers of cytokines and growth factors since that is an important function they serve in tissue, influencing the behavior of other cells. Adipose (fat) derived and bone marrow derived mesenchymal stem cells are cultured but produce dramatically different growth factor and cytokine patterns, consistent with the fact they perform markedly different functions in life.

It is now well recognized that fat is a pro-inflammatory “endocrine organ”, associated with increased incidence of many diseases that increase in incidence with age, most notably cardiovascular disease, diabetes, cancer and others. Bone marrow mesenchymal stem cells, on the other hand, are now recognized as the body’s commander-in-chief of healing in all tissues. Although these cells originate in the bone marrow, like red and white blood cells and platelets, they enter the vascular system enabling them to “patrol” all tissues.

When injury is encountered, bone marrow stem cells can differentiate into specific types of repair cells (e.g. bone, muscle, cartilage, skin, etc.) but that appears to be a secondary role. Their more important function is to orchestrate the healing process by acting as smart mini-drugstores, essentially instructing other cells how and when to participate in tissue repair. A chief function is modulating and dampening the inflammation associated with injury and the early healing phases. The growth factor and cytokine patterns of adipose and bone marrow mesenchymal stem cells in culture are below and consistent with their very disparate physiologic functions. The “teeter-totter” schematic is useful in demonstrating the comparative difference in the pro-inflammatory and  anti-inflammatory nature of the growth factors and cytokines produced by adipose and bone marrow stem cells. As discussed above, if the effort is to provide anti-aging benefit, particularly in a product intended for daily use, an anti-inflammatory bio-signal pattern is clearly preferable. Which brings us to PRP (platelet rich plasma), now popular for use with microneedling.

As mentioned above, PRP presents a conundrum of sorts. While true that platelets contain beneficial growth factors and cytokines, they also are sources of some of the most powerful pro-inflammatory cytokines, specifically TNF-α, Il-1, and Il-6. Furthermore, medical microneedling (at depths capable of producing injury to dermal capillaries) results in varying degrees of tissue bleeding that will itself result in platelet cytokine activation. Recall that the first phase of healing, whether a wound is sterile or contaminated, involves inflammation from platelet activation. The question: Is there value in promoting more robust inflammation through the use of topical PRP during microneedling? BFT is not convinced that is a good idea.

Nor is Dr. Lance Setterfield, the author of The Concise Guide to Dermal Needling, whose opinion is that inflammation should be minimized, not promoted. His hypothesis is that the injury of keratinocytes within the upper layers of the skin is sufficient to stimulate release of pro-healing stimulatory growth factors and cytokines and that deliberate use of pro-inflammatory topical adjuvants may be ill advised  and potentially detrimental.

For an in depth discussion of the science supporting the microneedling, BFT highly recommends his book which can be purchased through amazon.com or his website, www.acaciadermacare.com.

Fibroblasts, the First Cells Cultured to Obtain Growth Factors and Cytokines for Skincare is a Questionable Choice

Fibroblasts are poor producers of bio-signals. In a study that compared the production of important growth factors and cytokines by fibroblasts to that of bone marrow mesenchymal stem cells determined that the latter produces 15 to 50 times more bio-signals. The same study showed that bone marrow stem cells use bio-signals to promote fibroblasts to “proliferate, migrate and increase expression of genes important in wound repair.” It is clear from this study that fibroblast are the corporals taking orders their orders from bone marrow stem cells. (Mesenchymal stem cells induce dermal fibroblast responses to injury; Experimental Cell Research Volume 316, Issue 1, 1 January 2010, Pages 48–54 This is yet another article pointing to the important role bone marrow mesenchymal stem cells play in skin healing.  A number of earlier articles gave similar insight.

  • “A significant number of bone marrow cells traffic through both wounded and non-wounded skin.” J Cell Physiol. 2003 Aug;196(2):245-50
  • “The bone marrow contribution to normal skin and healing of cutaneous wound is substantially greater than the previously recognized.” Stem Cells. 2004;22(5):812-
  • “BM-MSC-treated wounds showed rapid closure and increased collagen synthesis, cellular proliferation and angiogenesis, and decreased expression of pro-inflammatory cytokines.” Tissue Eng. 2007 Jun;13(6)
  • “Bone marrow-derived cultured stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.” Tissue Eng. 2007 Jun; 13(6)
  • “Bone marrow stem cells participate in tissue repair through remodeling and regeneration of damaged areas.”  Stem Cell. 2008 Spring

An important article, supportive of the use of bone marrow stem cell conditioned media in anti-aging skincare products and microneedling, concluded: “…evidence shows that administration of BMSC-derived conditioned media can produce the same beneficial effects that are observed after stem cell therapy.” In other words, the nutrient broth from cell culture, after the cells had been filtered out completely, had the same efficacy as the cells themselves. Bone Marrow Research, Vol. 2011, Article ID 207326

Not Fish, Not Fowl

Which brings us to an interesting way in which to deliver cell culture-derived growth factors and cytokines to skin – and one BFT does not consider scientifically valid – slather on some hamburger! What, you say, can that possibly mean? Consider this: if one were to grow a large number of cells in culture, then discard, not keep the conditioned media in which they were grown, then freeze and thaw all the cells until they ruptured (scientifically termed “lysed”), you would have replicated the technique used by some companies to create topical skincare products. So instead of applying growth factors and cytokines, you’d be applying all the parts of the cell (membrane, cytoplasm, organelles, RNA, DNA), exactly what is in hamburger – all the cell and cell parts.

BFT sees two major problems with this as a concept in general, and one when considered as a strategy for use in microneedling.

1) The cell remnants applied to the skin, on a molecular basis, would be huge, unable to penetrate the stratum corneum to any meaningful degree.

2) As discussed many times on the blogsite, cells communicate using specific molecular bio-signals called growth factors and cytokines (and others.) Cell secrete these molecules into the fluid in which they live, which then diffuse to nearby cells, activating cellular membrane receptors and thereby influencing the behavior of the nearby target cells. This type of signaling, called paracrine signaling, is not likely to happen if the bio-signals secreted into the nutrient broth during culture are flushed down the drain and only the cellular “puree” is applied to the skin. Nature does not work that way.

3) When used with microneedling, such large molecular substances will have ready access to deeper layers of the skin since its barrier function has been temporarily breached by the thousands of tiny needle perforation. Such a scenario could possibly lead to genetically foreign material gaining access to the skin, leading to potential immunologic attack. Such attack is inflammatory in nature, not a good thing to promote improved aesthetics.

Fibroblasts from fetal skin and parthenogenic embryonic stem cells (unfertilized human ova chemically induced to proliferate), are used to make lysed cellular ingredients for skincare. On intact skin, BFT is of the opinion that improvements may be as much related to the “spackle” effect (like patching plaster cracks in a wall) as opposed to cellular responses to growth factors and cytokines. We are willing to learn, however, if someone affiliated with the companies making these products would care to discuss the science further.

What Should you Do?

A general consensus is beginning to develop among experts in the microneedling field and that is material foreign to normal human skin should not be applied during or for the first few hours after microneedling. In this way, the potential of foreign substances, a.k.a. “troublemakers”, entering into the skin will not exist, hence they will not be able to initiate adverse reactions. (Keep watching BFT, as we are now receiving more and more examples of adverse reactions from microneedling misadventures where substances foreign to human skin gained access, producing nasty allergic and inflammatory conditions, some quite severe and likely to lead to permanent disfigurement.)

What the BFT docs did.

We’re not secretive about our day jobs – we are physician/scientists who work with bone marrow mesenchymal stem cells. Our approach to microneedling was to create a topical product that contains only substances normally found in the skin: hyaluronic acid, growth factors and cytokines from laboratory culture of bone marrow stem cells, and for some product, additional TGF-beta 3, the superhero molecule of anti-inflammation. Many thousands of treatments over the past several months, very impressive results, and not a bad reaction among the lot.

51 Comments

  1. Mike says:

    What do you recommend for someone who has all kinds of scarring. from deep pits to shallow ones and pigmentation and rolling scars. Will micro needling and using a product containing “hyaluronic acid, growth factors and cytokines” help improve the appearance of the skin for someone who had acne in his early teens? I do not want to go the Laser route because the risks are too great at this point and I have come to accept my skin for what it is, but it doesn’t hurt to try and improve things. What size micro needle works best for scars? I have been using RETINA for the past 4 years everyday.

    • Cristina says:

      Microneedling with growth factor or with PRP Platelet Rich Plasma (vampire facial) Amazing results for acne scarred skin, stretch marks, anti-aging a collagen boster.
      Microneedling, way to go!

  2. Scott says:

    I’m hoping you can help clear up some misconceptions for what and when b-FGF should be used. This question is in regards to micro needling in particular.

    Many post-micro needling serums contain b-FGF, and others claim to promote it eg. snail snot cream.

    95% of micro needling treatments, however, are in hopes in increasing collagen, yet in every study I have seen regarding b-FGF it has been shown to directly inhibit collagen production.

    b-FGF has been shown to heal wounds particularly well and without scarring, so this leads me to believe that it should only be used when healthy skin is broken and the hope is to repair it back to the same condition before the immediate cause of breakage eg. after surgery to prevent a hypertrophic scar from forming at the point of incision.

    Is my thinking correct? And if so, would it also be beneficial following micro needling of a hypertrophic scar to reduce localized collagen and shrink the scar (similar to localized cortisone injection)? Or are collagen builders still preferred even when micro needling hypertrophic scars?

    Thank you for your guidance.

    • drjohn says:

      Scott- b-FGF is angiogenic (promotes blood vessels) and is not as collagenic as TGF. Good in an anti-aging mixture, but not so much on its own. The real star of the show in terms of scarring is TGF-B3. It is the single growth factor responsible for scar-free (non-fibrotic) healing in fetuses. It also shuts down TGF-B1, which is inflammatory, and responsible for all sorts of problems in skin. Collagen builders are good, because scars require remodeling. Chew up the old fibrotic tissues, and replace with fresh new collagen. Thus there needs also to be MMP’s (proteinases) and TIMP’s (inhibitors of proteinases) in the right balance to achieve aesthetically pleasing remodeling.

  3. Patrick says:

    Great article! You deliver scientific info in a way that most can easily understand – thanks! Everything I have read here is positive…my question is concerning the possibility of these GF overproliferating and potentially causing cancer. Most of the research I’ve read are studies based on short-term research (usually 3 months or less). Can you direct me to longer-termed data that could help ease my fears that long-term use of GFs can result in this unwanted adverse event? Thanks.

    • drjohn says:

      Patrick – great question. The honest answer is this – it depends on the source of the growth factors (and cytokines, and miRNA’s, etc). In fact, I cannot reassure you if the growth factors come from fat(adipose) stem cells, as there is a rapidly growing literature linking these to certain cancers. On the other hand, a cocktail of anti-inflammatory growth factors from bone marrow stem cells seems to have a tumor suppressive effect and is even being used to treat certain cancers. The difference lies in the secretome – which growth factors and cytokines are being released. Inflammatory or anti-inflammatory.

      It is time for us to address this topic more fully in a complete post. As a starting point I am going to link here to a very new scientific reference. But this is the tip of the iceberg. We will be revealing the whole picture in a post in the next few days.

      Leptin produced by obese adipose stromal/ stem cells enhances proliferation and metastasis of estrogen receptor positive breast cancers

      Contrast this with:
      Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells

      The best long term safety data comes from the fact that growth factor products have been in the marketplace for over a decade – and as far as I am aware there is not a single case report of a cancer of any sort being linked to such topical treatments. Of course, these are from fibroblasts and bone marrow stem cells; we are just now seeing the first adipose-based products hit the market. As you can guess, we have major concerns about those being applied daily to skin.

  4. Jae Z says:

    Hi Drs. John and George,

    Patrick’s and Scott’s questions have raised my own:
    I have been reading a lot about microneedling and am considering it for myself for mild to moderate rolling acne scars and post-acne enlarged pores. I am considering both ProCell and anteAGE MD which as far as I can tell are very similar – cytokines and GF derived from adult (not sure in ProCell’s case but I emailed Dr. Schwartz to ask) human bone marrow mesenchymal stem cells. (Actually, I would really love if you guys could tell me what the differences are – or may be – between ProCell and AnteAGE MD, as I think I have gotten pretty much to the limit of my ability to suss it out for myself).
    Based on the points Scott was bringing up, would you recommend AnteAGE MD for immediate post-needling treatment for acne scars, or only for anti-aging?
    And based on Patrick’s question, if someone had a BRCA1/2 gene predisposing them to breast cancer, would shallow (i.e. “home device” depth) microneedling of the chest area followed by application of AnteAGE MD or similar potentially make them less likely to develop breast cancer? Would applying AnteAGE MD topically (without needling) potentially have a similar effect?
    Thank you so much for your response, I would so appreciate answers. And thank you for your wonderful blog.

    • drjohn says:

      ProCell MD and AnteAge MD microneedling solutions are identical. Use either one for microneedling (during and for the first 4 hours or so thereafter, until the micro-channels are plugged and sealed). Then in the period between microneedling treatments use the stem | growth factor serum & accelerator system applied twice daily. Both AnteAge and ProCell sell those as well.

      Stem cell derived growth factors to reduce susceptibility to cancers is a theoretical possibility, but not enough data yet to make any scientific conclusions. But as long as the cytokine profile is anti-inflammatory, and does not contain excess adipokines (growth factors abundant in adipose stem cells) we believe them to be safe.

  5. Curious says:

    This was shocking to read:
    “As mentioned above, PRP presents a conundrum of sorts. While true that platelets contain beneficial growth factors and cytokines, they also are sources of some of the most powerful pro-inflammatory cytokines, specifically TNF-α, Il-1, and Il-6.”

    A PRP/vampire face lift was on my wish list for the future.

    Also this:
    “Fibroblasts from fetal skin and parthenogenic embryonic stem cells (unfertilized human ova chemically induced to proliferate), are used to make lysed cellular ingredients for skincare.”

    In light of the Ohui evaluation, this means that the stem cells that Ohui uses are suboptimal in relation to marrow stem cells. Since those types of stem cells take their order from marrow stem cells?

    Finally:
    “On intact skin, BFT is of the opinion that improvements may be as much related to the “spackle” effect (like patching plaster cracks in a wall) as opposed to cellular responses to growth factors and cytokines.”

    So using a marrow stem cell product will deeply rejuvenate the skin whereas a fibroblast one won’t?

    • drjohn says:

      Stem cell growth factor procedure serums are replacing PRP for skin. For orthopedics, PRP is still the thing. Skin doesn’t want inflammation.
      See Dr. George’s table Stem cells make 10-50 times as much of the good stuff as fibroblasts. Which cell is the healing cell of the body? makes perfect sense.
      Yes, fibroblasts are the worker bees. Stem cells are the queen bees.
      Fibroblasts do make rejuvenating GF’s and cytokines. Just 1/10 to 1/50 as much. Compare efficacy and cost.

  6. Curious says:

    With the PRP technique is it ok to use with other procedures like fat transfer to the face or other parts of the body?

  7. Curious says:

    Thank you so much Dr. John!

    I reread the article and keep referring back and forth between the two trying to get everything clear in my head. I really appreciate your clarification – it made it simple.

  8. Risa says:

    hey there! I just found your site and have already ordered a trial size of your anteage and can’t wait to try it! This is probably a stupid question but I read so many things on the internet about butylene glycol. most sites say it’s safe and others don’t and I know it’s in the accelerator cream and wondering why you chose this ingredient instead of another. I also find glycerin to be drying, not sure why I don’t have dry skin. on another note I have decided to dump all other skin sites and read yours 🙂

    • drjohn says:

      Risa, thanks for the vote of confidence. Butylene glycol is safe, and glycerine is drying but there are such tiny quantities in our product (a tag along from another ingredient that uses it as a carrier) that it should not be a worry. There any a number of superb moisturizing and moisture retaining ingredients in it as well.

  9. Anne says:

    Hi, I haven’t been able to find much information about how to use the Home Needling Solution. Is one entire 1.7 ml bottle intended to be used after medical needling? Cosmetic needling can be done up to every day, so unless the 1.7 ml is to be spread over multiple uses, the set would not last long. For medical needling, would you recommend using the Home Needling Solution immediately afterward, then waiting several hours before using other products? When can AnteAge Serum and Accelerator be used?
    How long the channels remain open is unclear to me; in Dr. Setterfield’s book, he says “the tiny holes caused by the [cosmetic] roller in the epidermal layer seal naturally within one hour” (p. 93), and under Medical Needling Protocol, “there is only a short window of time to apply any actives or serums as the needling channels generally close within about 10-15 minutes” (p. 102). So actives should be applied within 10-15 minutes, and any other products at least an hour later?
    Thanks, and I’m looking forward to trying these products!

    • drjohn says:

      Great questions, Anne. In terms of Dr. Setterfield’s book, he tells me this is not what he currently teaches in seminars, and that he is working on a revised edition. I believe he speaks to this on his website as well. Cosmetic microneedling (.25-.3 mm needles) penetrate the stratum corneum (SC) only, and thus do not present the same risk as medical needling at 0.5mm+. Also the channels are smaller, and SC is actually pretty swift in secreting ceramides and other gluey molecules to close any small gap. We recommend avoiding applying any “non-native” molecules until 2 hours after. Non-native means anything not made by humans naturally. Of course, the AnteAge microneedling solution is native human growth factors, cytokines, and hyaluronic acid. The serum and accelerator contain additional plant-derived materials, so we tell users to wait two hours before applying. The AnteAge home microneedling solution can be used sparingly and will last for 2-4 sessions. If you are needling every day, it would run out quickly. Dr Setterfield says you can needle cosmetically every day, but he himself only does a few times a week. I like to give the skin 3 or more days in between, because the therapeutic effect most certainly does not fade that quickly. Our best results are seen when you use the AnteAge serum/accelerator daily which I believe (in theory) extends the benefit of 0.25mm needling so that 1-2 per week is optimal.

  10. Tracy says:

    Hi and this is absolutely the more educational article I have read in a long time. I am looking at microneedling with PRP for sporadic under eye bags, fine lines, hyperpigmentation and general anti aging but I have rocacea and very youthful skin so have concerns about inflammation. I use skin medica today but haven’t seen much of a difference so my question is what would you suggest microneedling starting at a very low gauge and adding a serum or the PRP. Thanks!!

    • drgeorge says:

      Microneedling continues to impress us with its utility and effectiveness for most aesthetic concerns. Surface texture, pigment abnormalities, fine lines, and rosacea all respond well. We are not great fans of PRP since the trauma of dermal needling itself will cause damage sufficient to activate platelets when medical (longer) needle lengths are used. PRP has beneficial bio-signals but also is heavily laden with pro-inflammatory cytokines. We know from the fetus that inflammation is NOT needed for skin healing, and in fact can be counterproductive if chronic and persistent. Remember that inflammation plays a major role in promoting abnormal pigmentation and fibrosis. Occasional PRP sessions is unlikely to create problems. We just don’t think it is needed.

      As far as SkinMedica is concerned, their topical products with growth factors contain fibroblast conditioned media. Fibroblasts are very weak producers of growth factors and cytokines which is the major reason TNS serum has such a high concentration of conditioned media, which accounts for its “smelly socks” odor. Drjohn and Drgeorge, working in consultation with Dr. Lance Setterfield (the author of The Concise Guide to Dermal Needling) have developed microneedling products formulated especially for this purpose. By all means, do not apply topical products with ingredients that are foreign to the skin as you may be setting yourself up for nasty allergic reactions. BFT has had several women send us photos with serious reactions to products containing so-called snail growth factors. It turns out their is a 60-70% cross reactivity between snails and dust mites, one of the most common allergies. BFT covers all these topics. We suggest you poke around a bit and your questions will be answered in depth.

  11. Johan says:

    Great article, thanks for sharing. I designed a simple at home microneedle serum for use during application, 1.5mm depth needling with the purpose of improving acne box scars and hyperpigmentation. Trying to only use bio identical materials.

    Allantoin 0.3%
    Epidermal Growth Factor BT 0.00005% (Skinactives – think it would be beneficial?)
    Glutathione 1%
    Glycerin 3%
    Hyaluronic Acid 0.5% (Vegetable derived, high MW for gelling fx)
    L-Asorbic Acid 5%
    Lecithin 1%
    Sodium Lactate x% (x = amount required to get pH 5)
    Tocopherol 1%

    Made fresh with sterile techniques so preservatives are not required.
    Lechithin in this case would be derived from Soy, think that could cause problems? Better options could be Esters of monoglycerides of fatty acids (E472a-f) or Mono- and diglycerides of fatty acids (E471).

    • drjohn says:

      According to the world’s leading expert in microneedling, just about any non-native (non-human) molecule can be a troublemaker right after microneedling, until the channels created have clotted and closed off to reseal the barrier That includes even Vitamin C (which was the putative suspect in two cases of granulomatous reaction published in the AMA journal). And you are talking mere picograms of EGF so I see not much risk, but as we often say around here, EGF is not the best GF to use alone for microneedling (OK in combo with others), or for collagen synthetic boosting in general. I would think that to amplify microneedling’s know effect of collagen induction you would favor the FGF’s (fibroblast growth factors 1,2,5) since they are far more stimulating to collagen production. And to reduce scarring i would add a big dose of TGF-beta 3 which is the most anti-fibrotic (anti-scarring, scar-revising) of all the GF’s.

  12. Denne Adkinson says:

    Hello all, I’ve researched stem cell technology for anti aging and would like to begin microneedling however I order the ante age serum, accelerator and microneedling serum and after using the serum had an allergic reaction. I was so disheartened as I have been searching for the best product to use for microneedling. The only thing I can use safely is neocutic biocream, I cannot use any of the other products from their lives be without a reaction. Any ideas or recommendations on what I should do? Should I just have the physician use my biocream?

    • drgeorge says:

      Denne, how long after microneedling did you use the Serum? It is NOT intended for use until at least a day or so after treatment. Microneedling Solution is intended for use during and/or immediately after microneedling. Please give us more details on the timing of what your comment recounts.

  13. Linda Cezanne says:

    I was given a serum that contains Fibroblast Growth Factors after a brow microblading session. I was told to apply it twice a day for seven days but I feel I am having some sort of allergic reaction to it…my eyes feel strange and I have a slight headache around my forehead. Could it be the growth factor? I intend to stop using this serum and hope that these problems go away. Thank you for anything you can offer here.

    • drgeorge says:

      It’s difficult to say there is a relationship except for the fact your reaction seems local to the area treated. Have you tried stopping the product to see if the issue resolves? Could it be related to the pigments used? Hard to know. Certainly, the growth factors per se are hard to incriminate since if they are truly derived from fibroblasts, your own body produces the exact same growth factors, identical molecules. More likely, it could be some other ingredient.

  14. sam says:

    Hi Dr George and Dr J,

    I really like the formulation of the renewal serum. I have some concerns about the accelerator as I feel there may be one or two oils too many. I am considering using skin actives collagen serum ( with added allantoin and b5) and skinactives retin A serum as my PM routine. I will be doing this after using the ProCell Stem cells/Hyaluronic acid/growth factors with my microneedling device I will also be using the X-Taz Hyaluronic acid mask weekly.

    Here are the ingredients

    Collagen Serum
    Water, Seakelp (Lactobacillus/Kelp Ferment Filtrate) Bioferment, Glycerin, Sodium PCA, Magnesium Ascorbyl Phosphate, Hydrolyzed Collagen, Sodium Hyaluronate, Boswellia Serrata Extract, Centella Asiatica (Gotu Kola) Extract, Carnosine, N-Acetyl-D-Glucosamine, Niacinamide, Allantoin,Calcium Pantothenate,Betulinic Acid, Camellia Sinensis (Green Tea) Epigallocatechin Gallate, Glutathione, sh-Polypeptide-2, sh-Oligopeptide-1, Citric Acid, Phenoxyethanol (and) Caprylyl Glycol (and) Sorbic Acid.

    Vitamin A serum

    Water, Sodium PCA, Retinyl Acetate, Sodium Hyaluronate, Hydrolyzed Collagen, Hamamelis Virginiana (Witch Hazel) Water, Xylitol, Xanthan Gum, Phenoxyethanol (and) Caprylyl Glycol (and) Sorbic Acid.

    I would wait an hour or so before using this after the collagen serum.

    So I would use the Renewal Serum as normal AM. I would also every 2 days use my red and yellow led for 20 minutes each after using the collagen serum from skinactives.

    The only reason why I’m not sure about the accelerator lotion from procell is that I feel it’s got too many clogging ingredients. I feel it needs to be simplified a bit more. I’ve never been a fan of skincare that has too many ingredients, active or inactive.

    Would the two items above suffice for my PM routine?

    Kind Regards,

    Sami

    • drgeorge says:

      The two-part system we developed is sold under several brand names, including Procell. Our intention was to make skincare simple and convenient while providing the Who’s Who of actives that science has proven provide true benefits to aging skin. Our hero ingredient, bone marrow stem cell conditioned media, was selected since these are the very cells that provide the pro-healing anti-inflammatory bio-signals (cytokines and growth factors) that keep our skin soft, supple, and quickly healing throughout our early lives. Every living person has these same cells in abundance in youth but loses them at a dramatic pace with each passing decade. Applying these signals topically to the skin replenishes them, essentially turning back the aging clock on the skin. The cells of the skin respond regardless of whether the signals come from within or are produced in a laboratory in cell cultures. Since all the cells are removed and only the nutrient broth in which they were cultured in used, there is no worry about someone else’s cells or allergic reactions.

      Your question has to do with the other active ingredients, and it is clear you take the science seriously. In looking at the list of actives in the products you use, we see several of the ones we have selected for inclusion in our own products – certainly cannot take issue there and applaud you for thinking this through on a very high level. Not everyone has the knowledge or inclination to do so.

      Certainly, moisturization is important in skincare, both for preventative and restorative functions. We do have certain ingredients that play that role and for most people, the number of lipids (oils) is not excessive. For some, however, it might be. (Just to let you know, we are planning to launch a “light” version of the accelerator for those with oily skin.) Your choice of products for your PM routine is fine with several well thought-out actives. Cannot pick a fight about them. Hope this helps.

  15. Sam says:

    Thanks Dr 🙂

    Love this blog. Honest and clearly dedicated. Looking forward to seeing the rest of your work unfold. I love the renewal serum and it was worth every dime along with the microneedling solution. I’ve needled before with more basic, yet recommended ingredients, and the results aren’t looking as impressive as what i’m seeing just a week after needling.

    • drjohn says:

      Thanks for the good report, Sam. We see some rather dramatic results with microneedling with a human mesenchymal stem cell-based serum.

  16. Casey says:

    I’m new to stem cells and have been concerned about it stimulating cancer… I recently got a serum from NeoCell.. What do you think of this product, is it safe? They say they use Human Stem Cells http://neogenesis.com/

    • drjohn says:

      According to NeoCell label, the product contains conditioned media from human stem cells and human fibroblasts, while the company’s web site brags about two different stem cells used in the patented SR2M stuff. The problem is that 1. they don’t identify the type of stem cell or how it was processed, and 2. fibroblasts, while they share some properties with stem cells, are not actually stem cells. Many of those in your skin are terminally differentiated. The definitions are well established in cell biology such that that one has to doubt whether this company actually knows what they are doing. To call a fibroblast a stem cell may meet their marketing purposes, but is essentially incorrect. They are not alone – lots of other companies play footloose and fancy free with stem cell terminology – many of which have nothing to do with actual stem cells. Fibroblasts are the most abundant cell type in the human body. Common as dirt, you might say. Stem cells are more rare, and have considerably more value in regenerative medicine. Not knowing what type of stem cell makes up the other half of SR2M, one might speculate that it is adipose-derived stem cells (cheap, waste products of liposuction, easy to grow in culture). If so, we cannot be all that reassuring about your cancer question since AD stem cells create molecules called adipokines (e.g. leptin) in abundance, and these do have some well known cancer associations. Whether adipose or not, troubling that they do not reveal which stem cell niche they belong to as that determines much of the phenotypic secretome – the chemicals that are the actual bioactive factors in the product. As we have documented in these pages, we have even seen folks use embryonic stem cells and fail to inform users (or doctors or other scientists or the NIH) of the fact, leading to ethical dilemmas all around. They could have at least told us whether they are adult stem cells, but they don’t. Just list them right there on the label next to the fibroblasts that they are also (incorrectly) purporting to be stem cells. Are these fetal or neonatal fibroblasts? They don’t say. A number of cosmeceutical companies have used neonatal foreskin fibroblasts as their source for fibroblasts conditioned media, and hide that fact as well. Doesn’t play well in some circles. We need to do a post on “Foreskin Facials” here soon.

  17. Rima says:

    Docs. Wanted to share with you a typical response we face constantly from Medical Professionals:

    Typical conversation:

    ME TO DOC “we are not convinced that doing PRP with needling needling alone has sufficient benefit given the costs. There is some debate as to whether introducing PRP leads to the wrong kind of collagen production (scar collagen). As you noted yourself, microneedling results in “normal” collagen formation (because it triggers TGF-B3 — a molecule NOT found in platelets — which is anti-inflammatory). When dealing with older ( 35+) people, the question is whether or not PRP therapy ends up triggering TGF beta 1 (inflammatory) due to a diminished mesenchymal stem cell population. We have been looking at human derived GFs as an alternative to traditional PRP for facial rejuvenation. Loaded with TGFB3, it appears to be and we are seeing some excellent results.

    DOC TO ME: And the people who sell the growth factors are telling you that PRP is pro-inflammatory. That is convenient for them. Is there an independent source that states that PRP with needling is pro-inflammatory? I would certainly like to see it. Just looked at their website. They cite 5 papers. NONE OF THE PAPERS ARE PUBLISHED ANYWHERE!!!!! All papers are written by the same two people? Where are the other investigators? Why are the two people who profit from this product doing all of the “studies”? Where do they get their growth factors from? Other people’s bone marrow? No way I am using any human products on myself without them being my own. Their products are very expensive. Good luck getting people to pay $400 for a couple of tubes of serum derived from other humans. Tons of literature on PRP injected into the dermis for hair, and collagen regeneration over and above the needling alone. Papers date back to 2007. We cite all of them in our PRP CME course with links to full text and dozens of different authors.Just be very wary of any information from people who are trying to sell you stuff. We use SkinMedica products with our needling and add PRP if the patient wishes. Patients love it and get points for the products that they can use for Botox and Juvederm. If you get a cheap single spin machine, the PRP will be a very economical add-Don’t fall for sales pitches

    • drjohn says:

      REALITY TO DOC: The truth is inconvenient. There is an abundance of published work showing that the cytokines released during PRP processing are highly inflammatory. Would you like a sampling?

      Analysis of cytokine profile and growth factors in platelet-rich plasma obtained by open systems and commercial columns
      Human Inflammatory Cytokines IL-8, IL-1β, IL-6, TNF alpha, IL-12, IL-8, RANTES, MIG, MCP-1 all present in significant abundance

      Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors
      Proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, (TNF)-α and interferon (IFN)-α. TGF-β3 and IFNγ were not detected in any studied fraction.

      Growth Factor and Catabolic Cytokine Concentrations Are Influenced by the Cellular Composition of Platelet-Rich Plasma
      Catabolic cytokines were significant (MMP-9, IL-1β, TGFbeta-1).

      Comparison of the Cellular Composition and Cytokine-Release Kinetics of Various Platelet-Rich Plasma Preparations
      Very hight levels of highly inflammatory interleukin-1 (IL-1), and matrix metalloproteinase-9 (MMP-9)

      This would also be obvious by reading any textbook on the stages of healing (e.g. Robbins Pathology) as it has been known for a very long time that platelet degranulation and activation is the first step in the healing cacade, which is (by nature’s design) inflammatory.

      The other basics to know. Growth factors are the part that is responsible for the growth & repair, so the cytokines are along for the ride. So, what if you could isolate out just the growth factors and leave the cytokines behind? That is what we do in creating what we call “synthetic PRP”. We make a solution of pure GF’s that match those of PRP. You get all the benefits without the drawbacks.

      In orthopedic work you want the inflammation. You need that to repair tendons, cartilage, etc. That’s why PRP was developed. It also helps with fat graft transfers. But to use it on faces purely for rejuvenation is distinctly counterproductive. There we want anti-inflammation, not inflammation. For all the obvious reasons. Facial skin does not require inflammation. Growth factor stimulation under conditions of inflammation leads to fibrosis. Yes, you can hide wrinkles as the volume expands with fibroblast expansion. But years from now you are left with skin the texture of leather. Good luck with that.

      let us be clear on this: if we substitute anti-inflammatory cytokines & GFs instead of inflammatory PRP, there are no cells involved, so the “other people’s” serum claim is a total red herring. There is no risk of allergy, whether from human cell cultures or recombinant technology, as there are no cells (unlike PRP), just their biosignals. One suspects that the DOCS charging $400 to do the blood draws are the ones protecting their incomes.

      The argument in favor of hair is also specious – unlike facial skin, hair regeneration absolutely benefits from inflammatory cytokines to kick off the process. If PRP works for hair, it proves our point that it is inflammatory (truth is, most practitioners we talk to tell us it is not all that effective for hair anyway). The res of the argument is of equal emptiness scientifically speaking.

      And of course you can find elsewhere here on BFT the case series of folks developing severe facial granulomatous reactions to microneedling with products containing anything other than native human molecules.

      Happy to debate this any time, anywhere.

  18. Sam says:

    I have a question regarding PRP. Could there be a filtering process ( i think I read about it somewhere) where the PRP is modified to actually remove the pro inflammatory cytokines? It would seem like an obvious way of negating the issue at hand.

    All the best,

    Sam

    • drjohn says:

      It would involve a prohibitively expense set of technologies. Possible, not in any way practical. And why bother if you can just provide the growth factors without the problems, or better yet with anti-inflammatory cytokines.

  19. sam says:

    I agree. I just recall a Dr in the UK who is already making steps to doing this. Cheers doc.

  20. sam says:

    Just to follow up on an earlier post, when is the alternative accelerator serum( one for oily skin) going to be available?

    Cheers,

    Sam

  21. sam says:

    Hi Docs,

    Could you inject the Anteage MD micro needling solution in a mesotherapy like sense? Can it not be injected the same way PRP is? Intradermally? Could it even be mixed with PRP and injected?

    Kind Regards,

    Sam

  22. Lisa says:

    Good morning!
    Curious to know your thoughts on “nanotechnology” and the Rezenerate product -from their website: “does not penetrate into the dermis, but is designed to condition only in the outer layer of the stratum corneum” and is this something that could be used with AnteageMD/ProCellMD microneedling solution?
    Thank you!
    Lisa

    • drjohn says:

      We love nanochemistry and encapsulate many of our bioacives in structured nanolipid carriers. However, looking at this website, bit even sure what the product is. Mumbo Jumbo? —> “This “Golden Ratio” consists of the meticulously engineered structural shape of our “Nano Pyramids”; the cutting-edge raw materials used to create the them (a secret formula consisting of 99% mono-crystalline silicon); our iterated quantity of Nano Pyramids coupled with their exact spatial relationship; the specifically designed amplitude of the Rezenerate Chip’s oscillation upon the stratum corneum” Problem is, that actually relates to lithography in the semiconductor industry, and has nothing to do with dermatology in any published scientific literature. See e.g. Inverted random nanopyramids patterning for crystalline silicon photovoltaics. Mechanical oscillation? Sounds more like etching.

      “does not penetrate into the dermis, but is designed to condition only in the outer layer of the stratum corneum” sounds a whole lot like HMW HA, which is already present in the Anteage microneedling solution. It is the carrier for the growth factors.

  23. Bella says:

    Hi drjohn. I have enjoyed
    Reading this article. I, too, have microneedling with “growth factor” application scheduled for the end of the month. Now I am panicking after reading some of this. Should I be asking them what specifically they use after the needling? You always want to assume that a treatment is sAfe if you are going to a reputable medispa, but I don’t want to take any chances. Also I had a hard time
    Following this, but do
    You sell your
    Product or serum somewhere specifically?
    Thank you for you time

    • drgeorge says:

      By all means, we feel you should ask what is planned for your skin during those several hours when the barrier function is reduced due to the many thousands of tiny perforations that are created with microneedling. While we consider the aesthetic results nothing short of amazing when done properly and for the right indications, problems have occurred when topical products of the wrong type are applied. Some problems are serious and permanent. For that reason, you should apply ONLY products that contain ingredients that are physiologic and naturally occurring within human skin. We created our microneedling solutions with that caveat foremost in mind and have seen some stellar results. An international guru on the subject, Dr. Lance Setterfield, has written and lectured extensively on microneedling and consulted with us in the creation of our product. His text on microneedling is very technical with lots of deep science and should be on the reading list of every professional performing microneedling. Google his name and microneedling and it will pop up. If you want to contact us again, we can get you in touch with our team to find you a provider that uses our products or arrange for you to get it directly from our clinic. We prefer you seek it out from one of our growing number of practitioner resellers but are here to help if that proves difficult.

  24. Eric D R says:

    Are the products made by Skin Pro also good? I saw they have some with growth factors created in the lab, altho placenta is also mentioned (perhaps as the source of the types of growth factors they’re recreating).

    Today i had my first ever micro needling, done at a medSpa, and they used plant stem cell (from apples) serum, actually putting it on BEFORE the needling. I told them i think plant stem cells are bogus as an anti-aging agent, based on the research I’ve done and what scientists and dermatologists have said written about it online. But they said that’s just what they use. Hopefully they let me use a serum of my choosing next time. Interestingly tho, i just read somewhere that apples produce the same molecule that the human body uses to create tissue growth factors.

    And is putting the serum on beforehand a good idea?

    • drgeorge says:

      Skin Pro’s website describes a variety of peptides with Botox-like effect on reducing fine lines and wrinkles. The claimed mechanisms of action include binding to the nicotinic acetylcholine receptor at the neuromuscular junction and mimicking the effect of enkephalins, naturally occurring compounds that modulate pain perception and neuromuscular activity. Deep internet searches reveal some of this is found in patent claims.

      What jumped out, however, was their “stem cell technology” is based on our old friend, the rare Swiss apple tree, whose fruit allegedly resisted wrinkles in the cellar making it (ahem) perfect for preventing human skin from wrinkling. We’ve written about this elsewhere on BFT. Please take a look. You’ll see we’re not fans of anthropomorphic analogies between various plants and humans. They make no sense, so I must poo-poo the comment where you mentioned you read something about apples producing the same molecules the human body uses to create tissue growth factors.

      Plants “speak” with the bio-signals auxins, gibberellins and cytokinins, humans with cytokines, growth factors, interleukins, interferons, and others. The fact that plants and animals are all made up of organic molecules, and largely the same elements, does not negate how very different the two kingdoms are.

      Also, please read our posts on what not to put onto your skin for microneedling, Swiss apples are fine into the mouth, directly into the skin, not so much. During and immediately after microneedling, substances foreign to your skin have an easy path of entry where nasty things can happen. Please be careful.

  25. Kim says:

    Would you recommend using AnteAge microneedling solution after having a Profound (RF energy microneedling) procedure done? Could it potentially help with recovery?

    • drjohn says:

      We have lots of experience using AnteAge microneedling solution as a recovery complex after RF of all sorts. We have done studies in our own clinic that demonstrate the safety and efficacy. If someone reminds me I will post some pictures.

      • Mary says:

        I’m planning to get Forma RF and was going to just use the AnteAge MD after since it doesn’t seem like the skin barrier will be compromised. Will this be okay?

        • drjohn says:

          Start at bedtime. The heat of RF tends to disrupt the barrier chemically, although it usually restores within hours.

  26. Joan says:

    Hi:-). Just happened upon this blog and reading the conversations. I’ve searched the web for years looking for answers, education, etc on skin care, acne scarring, products, etc and have to say this blog has been the most helpful, educating and clear that I’ve found! Thank you!!! Grateful for the honesty and great questions.:-)

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