Using Growth Factors

By Dr Anna Hemming / 04 Nov 2019

In the second of her two-part article Dr Anna Hemming discusses the use of growth factors within aesthetic medicine

As detailed in my previous article published in the October issue of the Aesthetics journal,the depth of history and award-winning research behind the humble growth factor indicates how important these small molecules are.2-5 It is generally accepted that aesthetic medicine is becoming more and more focused on regenerative medicine and within this article I will explore the different types of growth factors, detail how to assess products for the best treatments and maximise the benefit to your patients. We know that as we age, we lose more cells than we can generate, the body slowly tires and cells become sluggish. We don’t have the stem cell reserves to maintain the demands of our skin and connective tissue to regenerate. 

As a result, our collagen, elastin and fibrin depletes, our bone changes shape, our fat pads decrease and our skin increases in laxity. Sagging and wrinkles continue as we age, unless, of course, we do something about it.

The introduction of growth factors into aesthetic medical treatments and skincare can increase the stimulation of growth factors supplied to our tissues and trigger further signalling, in order to regenerate our connective tissue production at an improved rate.6 By replacing or helping to regenerate the cells that the body loses in the natural ageing process, we can help treat ageing skin.

Growth factors in aesthetic medicine

The science behind the creation of stem cells through therapeutic cloning has many potential uses in the field of regenerative and aesthetic medicine.7 Stem cells are important as they allow our body to regenerate and repair damaged tissue, replacing cells, which turn over with age.

Growth factors play a fundamental role in this process as they provide the biochemical cues for stem cells to differentiate and are used to develop the right factors in tissue regeneration.8 The modulation of growth factors at the site of injury or within cells stimulates the most beneficial stem cell differentiation and tissue regeneration.8 Growth factors used in aesthetic treatments can be derived from different stem cell sources and not all stem cell-derived products are equal. It is important to select the correct stem cells to create growth factors, providing positive effects for regenerative medicine. There are various types of growth factors but less are suitable for aesthetic treatment:

  • Plant-derived growth factors are taken from the stem of a plant. They are then homogenised under high pressure resulting in dead plant cells, similar to plant extract, which contain antioxidants. There is no data comparing plant-derived products to conventional creams to regenerate skin or stimulate collagen. In my opinion, basic logical understanding of science should conclude that plant stem cells produce plant growth factors that regenerate plants.
  • Adipose-derived growth factors are strongly inflammatory fat growth factors that regenerate fat cells, not skin cells. They are obtained by liposuction waste and also used in fat grafting.
  • Snail-derived growth factors are highly inflammatory as they are produced when the snail is stressed.9
  • Human umbilical cord-derived growth factors produced from cord bank stores are a non-specific growth factor mix and their direct use is not allowed under EU law. In addition, extraction can be ethically challenging.10
  • Mesenchymal growth factors are very non-specific but generally anti-inflammatory, however not allowed under EU law.11

The ideal growth factor is anti-inflammatory and stimulates cell growth and repair.12 They target areas in need for regeneration and healing. Growth factors work alongside antioxidants, retinols, hydroxyl acids, plant extracts and protective SPF to help form and complete skin health treatments, hence why there are a number of home treatments including posttreatment serums and skincare. The mix of growth factors in the product should be anti-inflammatory, selective and targeted for wound healing and skin cell proliferation.

There are many growth factors found in the body, with different functions that act on different cell types. Growth factors work best and most effectively when paired up with other growth factors and are used synergistically.13,14 Solutions of single growth factor products do not supply the variety of signalling to induce the correct combined effects of growth, proliferation, differentiation, healing and inhibition of inflammatory cytokines.15 In my experience, the most common growth factors used in popular brands Calecim and Skin Genuity and the ones I’d recommend to look out for include, IGF-1, TGF-beta3, aFGF, bFGF, IL-10, EFG, PDGF KGF for skin rejuvenation and IGF-2, VEGF for hair due to their positive effects on stimulating hair growth.

Growth factor selection

Generating and using specific targeted antiinflammatory growth factors to act on and in the skin stimulates new collagen, fibrin and elastin, along with cell proliferation, speeding healing and enhancing rejuvenation of the skin. By selecting specific growth factors, the use of unwanted inflammatory growth factors and killer cells can be avoided, which can cause apoptosis and cell death.6

Preparations should specifically omit these inflammatory growth factors as they inhibit the healing process and are irritant, especially if included in a daily skincare routine. The next challenge, once you have selected the growth factor solution, is which method you wish to use to get the chosen growth factors to their target inside the skin. Growth factors are large molecules, and as a result are unable to pass into the skin unaided.

I have found that for best penetration into the skin, products can be injected, applied using trans-epidermal drug delivery system such as Plasma Shower or through nano encapsulation via nanotechnology such as liposomes. They can also be delivered through microneedling.16 Liposomes are a spherical vesicle with at least one lipid bilayer which can be used to administer nutrients or pharmaceutical drugs.16 They are hydrophobic and pass easily through the skin’s protective barriers. It is generally accepted that the correct growth factors minimise downtime by reducing negative elements in inflammation and help stimulate the cells needed to improve skin quality without inducing trauma. 

Areas where growth factors can be beneficial include facial rejuvenation, hair treatment, vaginal tightening and skin whitening,17-20 with more indications being researched. We know that stem cells release growth factors but platelets also release growth factors, and this is the basis of platelet-rich plasma (PRP) treatment. Platelets produce growth factors and their use has been well documented in aesthetic and orthopaedic medicine.6,8,21 Containing autologous non-selective growth factors when re-injected, the platelets trigger a cascade to promote healing and cell growth, however the growth factors produced are non-selective and the practitioner must be able to take a blood sample and have a centrifuge to spin the blood separating the plasma.21 Growth factors can also be applied following invasive treatments and within bespoke facials to aid skin healing or in daily treatment following skin trauma. For example, they can be used to decrease inflammation and swelling in the days after plasma blepharoplasty, fractional laser and other invasive skin treatments.

Once modified to penetrate the skin, targeted and focused growth factors are at the top of the pyramid of skin ingredients according to Mayoral et al., shown in Figure 1.22 This diagram was published in the Journal of Drugs and Dermatology in 2013 and used extensive research of scientific literature and study reviews of ingredients, formulations and technologies affecting the skin. The result of this was an effective yet simple tool to help professionally guide patients towards. It highlights the optimal, transform and fundamental use of topical products to achieve the best outcomes for skin health.22

Figure 1: The pyramid of skin ingredients22

Considerations

Critical considerations include the method within which the product enters the skin in the appropriate concentration, as well as ensuring any equipment has the correct FDA or CE marking and doesn’t put the patient at risk, which is beyond the scope of this article. Growth factor product selection should be from reputable safe and effective research-led companies. When selecting growth factor products, it is essential to understand the manufacturing process to ensure they comply with EU law.23 There should be product details and certification available from distributors.

Summary

I believe growth factors are part of the future in all aesthetic treatments and medical skin health programmes. Practitioners can consider using growth factors in a bespoke facial treatment or as part of a combined treatment plan. Serums with growth factors are available as add-on products for patients to take home and can be highlighted in clinic and unlikely to be sold on the high street. We can demonstrate their ability to enhance the effect of invasive therapies including microneedling and laser and help reduce the downtime associated with these procedures. For the successful use of growth factors in aesthetic medicine, the growth factors have to be able to enter the skin, have high enough concentrations to be effective, contain multiple focused and targeted growth factors, be easy to apply, available for all healthcare professionals to use, affordable and patiently friendly to allow for more at-home use.

References
  1. Hemming A, Understanding growth factors, Aesthetics journal, October 2019
  2. Goujon E, Recherches expérimentales sur les propriétés physiologiques de la moelle des os, J Anat Physiol, 1869
  3. Gurdon J.B, The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles, Journal of Embryology and Experimental Morphology, 1962
  4. Gurdon JB, The egg and the nucleus: a battle for supremacy, Development, 2013
  5. Takahashi, K., Yamanaka, S, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors, Cell, 2006
  6. Schuldiner M et al., Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells, PNAS, October 2000
  7. Mason C, Dunnill P, A brief definition of regenerative medicine, Regenerative Medicine, 2008
  8. Mao A S, Mooney D J, Regenerative medicine: Current therapies and future directions, Proc Natl Acad Sci USA, 2015
  9. Vuitton D et al., Cross-reactivity between terrestrial snails (Helix species) and house-dust mite (Dermatophagoides pteronyssinus), Allergy, 1998
  10. Dessels C, Factors influencing the umbilical cord blood stem cell industry: an evolving treatment landscape, Stem Cells Translational Medicine, May 2018 <https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.17-0244>
  11. Ullah I et al., Human mesenchymal stem cells - current trends and future, Bioscience Reports, Department of Theriogenology and Biotechnology, College of Veterinary Medicine, 2015
  12. Ueda M, A novel approach for skin rejuvenation by regenerative medicine: delivery of stem cellderived Growth Factors through an iontophoretic system, Int J Oral Maxillofac Implants, 2014
  13. Lindeboom J A., Mathura K R et al., Influence of the application of platelet-enriched plasma in oral mucosal wound healing, Clin. Oral. Implants Res, 2007
  14. Lacci K M, Dardik A, Platelet-rich plasma: Support for its use in wound healing, Yale J. Biol. Med, 2010
  15. Barrientos S et al., Growth factors and cytokines in wound healing, Wound Repair Regen, Sept 2008 <https://www.ncbi.nlm.nih.gov/pubmed/19128254>
  16. Kimball’s Biology Pages, Cell Membranes, January 2009 <https://web.archive.org/web/20090125224255/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.html>
  17. Aldag C et al., Skin rejuvenation using cosmetic products contaiing growth factors, cytokines and matrikines: a review of literature, Clin Comset Investig Dermatol, November 2016
  18. Lyons A et al., A randomised, double-blind, placebo-controlled, split-face study of the efficacy of topical epidermal growth factor for the treatment of melasma, Journal of Drugs in Dermatology, September 2018
  19. Garza L et al., Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells, Journal of Clinical Investigation, November 2010
  20. Isaza P et al., Use of growth Factors for Vulvo/Vagiinal Bio-Stimulation, Surgical Technology International, May 2019
  21. Tallquist M, Kazlauskas A, PDGF signaling in cells and mice, Cytokine & growth factor reviews, 2004
  22. Mayoral F, Kenner J, Draelos Z, The skin health and beauty pyramid: A clinically based guide to selecting topical skincare products, Journal of Drugs in Dermatology, April 2014
  23. Hilling C, Human growth factors as natural healers: current literature application, April 2013 <https://www.cosmeticsandtoiletries.com/formulating/function/active/premium-Human-Growth-Factors-as-Natural-Healers-Current-Literature-and-Application-204553091.html#targetText=The%20FDA%20allows%20the%20use,cosmetics%20in%20the%20European%20Union.>

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