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Science 2: Retinol and Stem Cell Factors

Experts say using retinol as an addition to your anti-aging skincare regimen has multiple benefits. But what is retinol? Simply, retinol is a type of Vitamin A, an essential molecule commonly used in skincare products.  Fun fact?  Its name is derived from “retina,” due to its role in your eye.  But it also has an important purpose in your skin; all cells involved in the maintenance of your skin have Vitamin A receptors and respond positively to it.  It’s a powerful antioxidant known for its ability to help reduce the appearance of fine lines, wrinkles, and other signs of aging. 

Retinol works by increasing hyaluronic acid synthesis [1], increasing epidermal thickness, and stimulating the production of collagen in the skin [2], which is a protein responsible for the skin’s firmness and elasticity. As you age, your body produces less and less collagen, which leads to the formation of fine lines and wrinkles. By increasing collagen production, the appearance of fine lines and wrinkles is diminished. Retinol also helps to exfoliate the skin and unclog pores. It does this by increasing cell turnover, which helps to remove dead skin cells and other debris from the surface of the skin. This can help to improve the texture of your skin and give it a more youthful appearance.

In addition to its anti-aging benefits, retinol also has anti-inflammatory properties [3]. This can be beneficial to those with acne-prone skin. Overall, retinol is an effective treatment for maintaining healthy skin.


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The downside to retinol use is it can sometimes cause redness, dryness, flaking of the skin, and an increase in photosensitivity. So how do you get the benefits of retinol without the downside? One way you can mitigate the detrimental effects of retinol is by using modified versions of the molecule.  Retinyl linoleate is a great example; it’s a fatty ester formed between linoleic acid and retinol [4].  Basically, it’s Vitamin A fused to an essential fatty acid that your skin needs anyway [5].  Why is it beneficial?  

Contribution By

Kristen F Rueb, MS and David L Stachura, Ph.D. on behalf of FACTORFIVE

In short, it’s a more stable version of Vitamin A that gets absorbed more slowly into the skin.  While it still has the same physiological effect as Vitamin A, it doesn’t cause the dryness and dehydration that usually accompanies retinol application [6-7].  It’s a gentler way of reducing the appearance of fine lines and wrinkles while still exfoliating the skin.

Another great way to get the benefits of retinol without the negative effects is to pair it with other products that soothe the skin.  A great ingredient to add?  Human stem cell factors!  Human stem cell factors have gained a lot of attention in recent years due to their ability to rejuvenate and improve the skin’s appearance [8-10]. These proteins are naturally produced by your skin’s stem cells, which play a crucial role in the growth, development, and repair of tissues. They are secreted by human stem cells that live in the lowest layer of your skin [11], which means that they are biologically compatible with the human body (unlike plant stem cell growth factors).  

How do they work with retinol?  

Well, stem cell factors also possess antioxidant activity [9-10], help increase the extracellular matrix of your skin [12], and stimulate the growth of epidermal cells.  In addition, the factors secreted by stem cells are anti-inflammatory [8], which soothes the redness, burning, irritation, and photosensitivity caused by retinol application.  Importantly, they are angiogenic and immunomodulatory [9], increasing blood flow and allowing cellular repair and growth.  In essence, human stem cell factors should dramatically increase the health of your skin, especially as it ages and the body makes less and less of these compounds on its own. 

In conclusion, combining retinol with an essential fatty acid and human stem cell factors is a winning combination that will help make your skin look healthier, more youthful, and radiant.  While retinol on its own is a formidable ingredient in skincare, the addition of stem cell factors makes it even better for promoting healthy skin.

Works Cited

  1. Ma’or Z, Cohen D, La’or-Costa Y. and Portugal-Cohen M. (2020) Safe Retinol-Like Skin Biological Effect by a New Complex, Enriched with Retinol Precursors. Journal of Cosmetics, Dermatological Sciences and Applications, 10, 59-75.
  2. Kong R, Cui Y, Fisher GJ, Wang X, Chen Y, Schneider LM, Majmudar G. A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. Journal of Cosmetic Dermatology. 2016 Mar;15(1):49-57. doi: 10.1111/jocd.12193. Epub 2015 Nov 18.
  3. Millikan LE. The rationale for using a topical retinoid for inflammatory acne. American Journal of Clinical Dermatology. 2003;4(2):75-80.
  4. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 6440169, Retinyl linoleate. Retrieved May 10, 2023 from https://pubchem.ncbi.nlm.nih.gov/compound/Retinyl-linoleate.
  5. Whelan J, Fritsche K. Linoleic acid. Adv Nutr. 2013 May 1;4(3):311-2. doi: 10.3945/an.113.003772. PMID: 23674797; PMCID: PMC3650500.
  6. McCusker MM, Grant-Kels JM. Healing fats of the skin: the structural and immunologic roles of the omega-6 and omega-3 fatty acids. Clin Dermatol. 2010 Jul-Aug;28(4):440-51. doi: 10.1016/j.clindermatol.2010.03.020. PMID: 20620762.
  7. Vaughn AR, Clark AK, Sivamani RK, Shi VY. Natural Oils for Skin-Barrier Repair: Ancient Compounds Now Backed by Modern Science. Am J Clin Dermatol. 2018 Feb;19(1):103-117. doi: 10.1007/s40257-017-0301-1. PMID: 28707186.
  8. Son WC, Yun JW, Kim BH. Adipose-derived mesenchymal stem cells reduce MMP-1 expression in UV-irradiated human dermal fibroblasts: therapeutic potential in skin wrinkling. Biosci Biotechnol Biochem. 2015;79(6):919-25. doi: 10.1080/09168451.2015.1008972. Epub 2015 Feb 16. PMID: 25685961.
  9. Kim WS, Park BS, Kim HK, Park JS, Kim KJ, Choi JS, Chung SJ, Kim DD, Sung JH. Evidence supporting antioxidant action of adipose-derived stem cells: protection of human dermal fibroblasts from oxidative stress. J Dermatol Sci. 2008 Feb;49(2):133-42.
  10. Zhang S, Dong Z, Peng Z, Lu F. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose. PLoS One. 2014 May 15;9(5):e97573.
  11. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002 Dec;13(12):4279-95.
  12. Novoseletskaya E, Grigorieva O, Nimiritsky P, Basalova N, Eremichev R, Milovskaya I, Kulebyakin K, Kulebyakina M, Rodionov S, Omelyanenko N, Efimenko A. Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli. Front Cell Dev Biol. 2020 Sep 22;8:555378.
  13. Ivanova-Todorova E, Bochev I, Mourdjeva M, Dimitrov R, Bukarev D, Kyurkchiev S, Tivchev P, Altunkova I, Kyurkchiev DS. Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells. Immunol Lett. 2009 Sep 22;126(1-2):37-42. doi: 10.1016/j.imlet.2009.07.010. Epub 2009 Jul 30. PMID: 19647021.
  14. Melief SM, Zwaginga JJ, Fibbe WE, Roelofs H. Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts. Stem Cells Transl Med. 2013 Jun;2(6):455-63. doi:

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