Prompted by the question (see below) posted by reader Holly as a comment to our post entitled Bioeffect EGF Controversy, we invited our highly respected colleague Dr. Lance Setterfield, guru of all things microneedling and related skin care topics, to join us here at BFT. He brings a new and different perspective to the science that interests us. All the more fun because science shines best when it is debated, to bring out the fine points of what is (and often what is not) known. Take it over DrLance….
“What do you think about micro needling / roller while using EGF? Does that alter what layer the EGF works at? I see this on the web used together. I also see it used for alopecia (needling) with serums so isn’t that the opposite of losing hair over time with EGF use? Is it the combo used together that changes the dynamics? I’ve never used any of them – just curious about micro needling for wrinkles and what I should use on the face while needling. I don’t want to use something unsafe. Thanks.”
On the surface (no pun intended), this may seem fairly straightforward, but it is extremely complex. The question above presupposes that EGF in a skin care product works to begin with. I am not saying that one could not get a result, but all the planets have to be aligned, so to speak. Unfortunately, the skin care industry tends to oversimplify things and explain them in scientific ways so as to add credibility to a concept, but in essence it is mostly marketing spin to sell a product. This is particularly true when it comes to stem cells, growth factors, and cytokines because they are new buzz words, and, together with gene therapy, represent the future of skin care. The stakes are high.
Epidermal Growth Factor was one of the first growth factors to be isolated from a number of sources, e.g. plants, E-Coli, etc., and added to skin care products. It is probably the most common growth factor in products today. The marketing premise starts here:
EGF is a growth factor that is essential in the regulation of cell growth, proliferation, differentiation, and survival. It promotes synthesis of DNA, RNA, hyaluronic acid, and Hydroxyproline.
So far, so good. But this is where the wheels fall off. Here are the issues.
EGF does not accomplish these things in isolation. Think of it this way. If growth factors and cytokines are signaling molecules that facilitate communication between cells, EGF is the area code in a phone number, but if you don’t punch in all the other numbers, you won’t make contact and there will be no outcome. Not all phone calls have a happy ending either. Once you get through, there may be other factors involved that can result in a negative outcome. EGF is one of those growth factors that can work for good (rejuvenation) or bad (cancer), and much of the outcome depends on the balance or imbalance of many other factors.
- 2. Bio-mimicry:
Growth factors and cytokines bind to receptors to accomplish outcomes. In other words, they are like keys that turn things on and off. They have to fit the keyhole exactly. The question becomes whether or not growth factors derived from plant cells are identical to those from human cells?
Outcomes are dose-dependant. Do all cosmetic products contain enough EGF to make a difference?
- 4. Balance of nature:
Are all the other elements that combine with EGF in any scenario present in quantities that represent a synergistic balance? For instance, too many pro-inflammatory growth factors and cytokines will lead to premature aging, scarring, or even cancer.
- 5. Deductions based on a name:
Studies show that EGF results in cell growth, proliferation, differentiation, and survival. But one study showed that “when cultured at 37 degrees C, keratinocytes formed a well-differentiated epidermis whether EGF was present or not.”  Yet another study showed: “Short-term growth of keratinocytes in a chemically defined medium demonstrated that neither EGF nor IGF-I alone could support significant keratinocyte spreading or proliferation, but that a combination of EGF with IGF-I or high-dose insulin could.” 
Thus, cell activity may be due to other factors besides the obvious.
- 6. Self-Regulatory via biofeedback mechanisms:
“EGF induces DUSP’s which are phosphatases that limit the EGF signal transduction in a feed-back loop.”  So, at what point does too much of a good thing become a bad thing, especially in the context of needling where natural EGF is released in significant amounts?
- 7. EGF may induce or suppress the same genes:
EGF influences about 1100 genes. Meta-analysis shows about 520 genes are induced while 580 are suppressed by EGF treatment in human epidermal keratinocytes. 44 are both induced and suppressed, depending upon the timeline of the treatment. Which outcomes will prevail depends on additional EGF-independent signals affecting the keratinocytes. 
With regards to the question about EGF treatment for alopecia, again, it is a combination of factors that dictates outcome. One study used EGF in isolation, injected in angora rabbits to facilitate an increase in depilation. The mechanism of action involves inhibition of mitoses within the cell population of the follicle bulbs causing follicle regression. 
Other studies, however, show epidermal growth factor functions as a biologic switch that is turned on and off in hair follicles at the beginning and end of the anagen phase. In addition, EGFR (Epidermal Growth Factor Receptor) signaling is indispensable for the initiation of hair growth.  Patients that are treated with EGFR inhibitors for cancer may develop alopecia , confirming the positive effect that EGF can have on hair growth. The positive results seen with needling and PRP for hair restoration, however, are predominantly due to the activity of other growth factors and cytokines. This study pertaining to adipose stem cells showed “VEGF controls hair growth and follicle size by angiogenesis in a VEGF transgenic mouse model (30). In addition, PDGF and its receptors are important in follicular development, and PDGF isoforms induce and maintain the anagen phase in murine hair follicles (27). IGF-I also up-regulates hair follicle growth in various systems.” 
As to your question about what to use on your face that is safe to combine with needling, this is a topic too vast to embrace in this format of discussion. I address these concerns in a section of “Concise Guide to Dermal Needling – Expanded Medical Edition” (Pages 64-77) and excerpts can be viewed here: http://www.needlingguide.com/book/
In summary, listing individual ingredients on a skin care product label to create a distinctive difference disregards the complexities of biochemistry, which is borne out by the reality that we struggle to get results in our clinical practices despite the amazing advances in science.
 Epidermal growth factor and temperature regulate keratinocyte differentiation. Ponec M1, Gibbs S, Weerheim A, Kempenaar J, Mulder A, Mommaas AM.
Arch Dermatol Res. 1997 May;289(6):317-26
 Synergistic Effects of Epidermal Growth Factor (EGF) and Insulin-Like Growth Factor I/Somatomedin C (IGF-I) on Keratinocyte Proliferation May Be Mediated by IGF-I Transmodulation of the EGF Receptor Jeffrey F Krane, Daniel P Murphy, D Martin Carter and James G Krueger Journal of Investigative Dermatology (1991) 96, 419–424; doi:10.1111/1523-1747.ep12469799
 Profiling and metaanalysis of epidermal keratinocytes responses to epidermal growth factor. Miroslav Blumenberg. Published online: 8 February 2013
 Epidermal growth factor (EGF) facilitates depilation of the Angora rabbit. G.P.M. MOORE, R.-G. THÉBAULT J. ROUGEOT and P. VAN DOOREN Ann. Zootech., 1987, 36 (4), 433-438
 Epidermal Growth Factor as a Biologic Switch in Hair Growth Cycle* Kingston K. L. Mak and Siu Yuen Chan. First Published on April 24, 2003, doi: 10.1074/jbc.M212082200. July 11, 2003 The Journal of Biological Chemistry, 278, 26120-26126.
 Nonscarring inflammatory alopecia associated with the epidermal growth factor receptor inhibitor gefitinib. Julia E. Graves, MD, Beverly F. Jones, MD, PhD, Anne C. Lind, MD, Michael P. Heffernan, MD. Journal of the American Academy of Dermatology Volume 55, Issue 2, August 2006, Pages 349–353
 Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion. Byung-Soon P ark, Won-Serk Kim, Joon-Seok Choi, Hyung-Ki Kim, Jong-Hyun Won, Fumio Ohkubo, and Hirotaro Fukuoka. Biomedical Research 31 (1) 27-34, 2010