Role of growth factors in skin creams

Author: Anoma Ranaweera Medical Writer, Auckland, New Zealand. DermNet NZ Editor-in-Chief: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand. 2011. Updated January 2019.


What are growth factors?

Growth factors are proteins that regulate cellular growth, proliferation and differentiation under controlled conditions. They play an essential part in maintaining healthy skin structure and function.

Growth factors are secreted by all cell types in the epidermis and dermis including keratinocytes, fibroblasts and melanocytes.

Why do we need growth factors in skin care products?

Growth factors are not growth hormones. They are natural substances made by the skin cells that support the repair of damaged skin, as a result of ageing or environmental factors. They promote the formation of collagen and elastin to provide firmness and elasticity.

Cells in ageing skin make fewer growth factors than cells in youthful skin. One approach to support the levels of skin rejuvenation is to regularly use skin care products with a high concentration of stable growth factors. Daily use of skin care products containing growth factors is known to help reduce the appearance of fine lines, wrinkles and improve skin tone and texture.

Do growth factors work?

There’s debate among dermatologists as to whether topically applied growth factors can penetrate the skin enough to be effective. It has been asserted that growth factors have a large molecular size that prevents them from entering the epidermis. However, several clinical studies, over the past 15 years, have highlighted the benefits of topically applied growth factor products showing improvements in the appearance of fine lines, wrinkles, texture, and discolouration. Combinations of growth factors with antioxidants (eg, vitamin C) and peptides (eg, cytokines) tend to show results sooner, typically within 4–8 weeks.

It has been hypothesised that when growth factors are applied to the skin in high concentrations, a  small fraction penetrates the superficial epidermis, and initiates a communication chain that leads to stimulation of dermal fibroblasts to produce collagen.

Growth factors used in conjunction with needling, laser resurfacing, fractional resurfacing or injection are more effective than when used in creams alone.

Where do growth factors in skin care products come from?

Advances in biotechnology over the past decade have created multiple sources of growth factors. They can be derived from several different human cells grown in a laboratory (skin cells, bone marrow stem cells, fat stem cells), extracted from one’s blood (PRP - Platelet Rich Plasma), or bioengineered from non-human sources such as snails and some plants. However, fat stem cells are likely to produce growth factors that help the functioning of fat cells, and bone marrow stem cells are likely to produce growth factors that improve the functioning of the bone marrow.

Ideal growth factors for the skin would be produced by fibroblasts.

In a comparative study published in 2017 dermal growth factors outperformed growth factors derived from other kinds of human stem cells, like fat cells, as well as non-human sources of stem cells, such as snails and plants.

How do growth factors work?

  • They stimulate biochemical pathways that promote skin tissue repair and regeneration.
  • They promote the formation of collagen and elastic fibres which give the skin its softness and suppleness.
  • Synergistic interaction of multiple growth factors with other proteins in epidermis and dermis results in skin repair and regeneration.
  • No single growth factor is solely determinant in the outcome of skin rejuvenation.
  • Successful repair of damaged skin and collagen synthesis require the involvement of growth factors and cytokines.

Neocutis SA (Switzerland) and Defenage (Carlsbad, California, USA) have developed products containing a mix of proprietary and non-proprietary peptides that stimulate the production of one’s own internal growth factors instead of adding growth factors externally.

What are the uses of topical skin creams containing growth factors?

Topical skin creams containing endogenous growth factors are used as cosmeceuticals. Skin creams containing a physiologically balanced mixture of growth factors and other proteins are available to reverse the signs and symptoms of:

  • Intrinsic skin ageing mediated by the process of natural ageing
  • Extrinsic skin ageing mediated by environmental factors.

Intrinsic ageing

In intrinsic skin ageing:

  • There is a programmed tendency for cells to stop proliferating or dividing
  • The amount of collagen decreases in the skin over time (about 1% a year)
  • The degradation of collagen increases so that overall, the dermis thins by 20% in older people
  • Elastic fibres become damaged causing laxity.

Extrinsic ageing

In extrinsic skin ageing, external factors are responsible for the signs of ageing, particularly ultraviolet radiation due to sun exposure and tobacco smoke. Extrinsic factors cause degradation of collagen and other factors leading to:

What are the effects of growth factors in skin creams?

Controlled clinical studies have shown that the application of skin creams containing growth factors:

  • Reduces the appearance of fine lines and wrinkles as a result of new collagen synthesis
  • Improves the appearance of age spots and evens out pigmentation
  • Reduces skin roughness
  • Improves skin texture and elasticity
  • Improves skin smoothness and tightness.

What are the growth factors in commercially available skin creams?

Several topical skin creams contain a single growth factor or multiple growth factors and cytokines are available for sale over the counter. They may also contain soluble collagen, matrix proteins and antioxidants to neutralise free radicals. None of the products is FDA approved. 

Some growth factors used in skin creams
Growth factorFunction
Transforming growth factor beta (TGF-B) Stimulate collagen secretion
Vascular endothelial growth factor (VEGF) Stimulate new blood vessel formation
Hepatocyte growth factor (HGF) Stimulate new blood vessel formation
Keratinocyte growth factor (KGF) Stimulate epithelial cell growth
Interleukins (IL-6, IL-7, IL-8) Reduce inflammation
Basic fibroblast growth factor (bFGF) Promote the creation of blood vessels
Insulin-like growth factor 1 (IGF1) Promote cell growth and multiplication
Platelet-derived growth factor AA (PDGF-AA) Regulate cell growth and division
Transforming growth factors (TGF-B2 and B3) Stimulate collagen secretion
Granulocytemonocyte colony stimulating factor Increase number of white blood cells

How safe are skin creams containing human growth factors?

Human growth factors are messengers received by specific receptor sites on the surface of skin cells stimulating cell division and multiplication. For example, transforming growth factor (TGF) stimulates collagen production and epidermal growth factor stimulates skin-cell production.

Most of the research on human growth factors for skin has looked primarily at the issue of wound healing, and at short-term use. Much remains unknown at this time, especially regarding long-term risk or stability, when growth factors are used in cosmetics and applied to the skin. Well-controlled clinical studies are lacking.

Current concerns about using growth factors for cosmetic purposes include:

  • In skin-care products, growth factors would be used repeatedly, and possibly over long periods.
  • If they cause cells to over-proliferate, they might cause cancer or other health problems.
  • In the case of TGF, which stimulates collagen production, it can encourage scarring, because scars are the result of excessive collagen production.
  • It is not known whether growth factors contained in cosmeceuticals are stable, can be absorbed adequately, or exert a functionally significant outcome to induce dermal remodelling and reverse photoageing.

 

Related information

 

References

  • Mehta RC, Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatologic Therapy 2007; Published online; DOI: 10.1111/j.1529-8019.2007.00149.x. PubMed.
  • Sundaram H, Mehta RC, Norine JA, Kircik L, Cook-Bolden FE et al. Topically applied physiologically balanced growth factors: a new paradigm of skin rejuvenation. J. Drugs Dermatol. 2009 May;8(5 Suppl Skin Rejuvenation):4-13. PubMed.
  • Gold MH, Goldman MP, Biron J. Efficacy of Novel Skin Cream Containing Mixture of Human Growth Factors and Cytokines for Skin Rejuvenation. Journal of Drugs in Dermatology 2007; 6 (2):197-202. PubMed.
  • Díaz-Ley B, Cuevast J, Alonso-Castro L et. al. Benefits of plasma rich in growth factors (PRGF) in skin photodamage: clinical response and histological assessment. Dermatol Ther. 2015 Jul-Aug; 28(4):258-6. PubMed
  • Park JW, Hwang SR, Yoon IS. Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration. Molecules. 2017 Aug; 22(8): 1259. PubMed Central
  • Husein El Hadmed H, Castillo RF. Cosmeceuticals: peptides, proteins, and growth factors. J Cosmet Dermatol.2016 Dec; 15(4):514-519.PubMed
  • Fabi S, Sundaram H The potential of topical and injectable growth factors and cytokines for skin rejuvenation. Facial Plast Surg. 2014 Apr; 30(2):157-7. PubMed

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