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Peptides, Stem Cells & Growth Factors - Volume 1, Issue 4 November 2022

Peptides, Stem Cells & Growth Factors - Volume 1, Issue 4 November 2022

In our fourth newsletter, we'll discuss some of the newer (1980’s to current) ingredients in skincare.  With advances in the use of peptides, stem cells, and growth factors, you can change not only the appearance of your skin but how it behaves. Sound high-tech and revolutionary? That’s because it is!

The science is complex.  In essence, it’s all about proteins (“the building blocks of life”). Proteins are comprised of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. It’s the sequence of amino acids that determines each protein’s unique function.

For example, take collagen.  Collagen is a protein made of three polypeptide chains and contains 19 amino acids. It provides structure to the skin and accounts for around 75% of its weight. But the importance of proteins in skincare goes far beyond collagen alone.  Some 8,987 proteins in the outer epidermis (stratum corneum) and 9,140 proteins in the inner epidermis (comprising cell layers down to the basal membrane) have already been identified[1].

PEPTIDES – “The Communicators”
The development of synthetic peptides for skincare dates back to the 1980s.

Peptides are short chains of amino acids.  In literature they are often referred to as matrikines due to their smaller size. These short amino acid chains are one of the most promising anti-aging treatments because they can penetrate the top layer of your skin and send signals to cells to produce more collagen.  Some peptides you can find in cosmeceutical-grade skin care products, categorized according to their mechanism of action, include:

  • Signaling peptides – connect with receptors on cells within the skin and in turn encourage the production of a particular protein (e.g. collagen, elastin, hyaluronic acid, proteoglycans, glycosaminoglycans, and fibronectin).

    Examples: carnosine, copper tripeptide-1, palmitoyl tetrapeptide-7, palmitoyl oligopeptide, palmitoyl tripeptides 1 and 3/5, palmitoyl pentapeptide–4, acetyl tetrapeptide-9 and 11, Tetrapeptide–21, hexapeptide-11, lipospondin, palmitoyl hexapeptide–12, and tetrapeptide PKEK.

    BevTip:  Signaling peptides have been shown to produce results similar to retinol, so they can be a good alternative for people with sensitive skin who want the anti-aging benefits of retinol without its potentially harsh side effects. 

  • Carrier peptides – help transport important trace elements (e.g. copper, magnesium) into your skin cells.

    Examples: tripeptide-1, copper tripeptide-1 (GHK-Cu), manganese tripeptide-1.

  • Neurotransmitter-inhibiting peptides – target expression wrinkles by inhibiting the body’s signals that tell facial muscles to contract, resulting in a ‘botox-like’ effect.

    Examples: Acetyl hexapeptide-3 or acetyl hexapeptide-8 (a peptide which is a fragment of SNAP-25, a substrate of botulinum toxin), acetyl tetrapeptide-5, pentapeptide-3 and 18, dipeptide-2. tripeptide-3, palmitoyl hexapeptide–52, and acetyl octapeptide-3. 

  • Enzyme inhibiting peptides – prevent the activity of particular enzymes that participate in skin aging. Tyrosinase, for example, is responsible for melanin production, and it is often desirable to inhibit its function.

    Examples:  soybean peptides, rice peptides, possibly tetrapeptide PKEK

    Fewer studies have been conducted in this category; however these peptides show promising results.

Unfortunately, we produce less and less collagen as we age, and collagen fibers become increasingly disorganized, leading to sagging, wrinkled skin.

BevTip:  Peptides and retinoids are not only safe to use together but might just be the ultimate dynamic duo for youthful skin.  You'll need to use most formulations for at least a month to see results, and you should exfoliate regularly to help as many as possible get past the first layer of your skin.  I should also mention this is a lifelong commitment, so establish skincare routines with that in mind.

STEM CELLS – “Differentiators”
Researched for decades.  Advancing skincare since 2001.

Stem cells are a population of undifferentiated cells that undergo asymmetric cell divisions, whereby they divide to self-renew and give rise to a progenitor cell, which can differentiate into many different types of cells, such as skin cells.

Majhi, Prasanta. (2020). STEM CELLS & ITS APPLICATION.

Credit: Majhi, Prasanta. (2020). STEM CELLS & ITS APPLICATION.

Stem cells are predominantly derived from two general groups, embryonic and adult.  Both types share the ability to self-renew and differentiate into specialized cell types, but they differ in other attributes. 

Embryonic stem cells are derived during early development at the blastocyst stage and are pluripotent, meaning that they can differentiate into any cell type.  Adult stem cells can be derived from the brain, bone marrow, blood, skeletal muscles, adipose tissue, ova, skin and the liver.  The ability of adult stem cells to differentiate is limited; these cells can be either multipotent or unipotent.  

In 2012, the Nobel Prize in Medicine or Physiology was awarded jointly to Dr. Shinya Yamanaka and Sir John B. Gurdon “for the discovery that mature adult stem cells can be reprogrammed to become pluripotent.”  [2].  Induced pluripotent stem cells are created in the laboratory, a happy medium between adult stem cells and embryonic stem cells.  This fact should alleviate some of the ethical concerns surrounding human embryonic stem cells.

Interesting Fact:  Our body’s existing stem cells age.  The number of stem cells in our bone marrow drops tremendously (10X) from birth to our teenage years and another 20X by the time we are 80! 

Coming back to skincare…. Bone marrow derived mesenchymal stem cells (BM-MSCs) are multipotent and can differentiate into many different cell types responsible for the repair or growth of bone, cartilage, muscle, tendons, ligaments, connective tissue and highly specialized epithelial cells (skin cells).  Once differentiated, that cell remains part of the new tissue when repair is complete.

Brave, Hosanna & MacLoughlin, Ronan. (2020)

Credit: Brave, Hosanna & MacLoughlin, Ronan. (2020)

Stem cells are factories that secrete small biologically active proteins called cytokines.  Stem cell cytokines generally fall into 3 categories:  pro-inflammatory, anti-inflammatory and growth factor cytokines (more on these later). 

All cultured cells (human, plant, or animal cell that has been adapted to grow in the laboratory) produce many cytokines so as a rule of thumb, you want the collective pattern to be net ‘anti-inflammatory.’

Sanderson, MD, John; Taylor, MD, George, Cellese Regenerative Therapeutics, (2017)

Credit: Sanderson, MD, John; Taylor, MD, George, Cellese Regenerative Therapeutics, (2017)

Human BM-MSCs are the preferred cell type for anti-aging and post procedure because of their anti-inflammatory cytokine pattern.  How are they obtained?  Bone marrow is harvested (usually through a hollow needle) from young donors (usually in their early 20’s).  The cells are cultured in a nutrient broth.  Ultrafiltration removes their cells and remnants.  Cytokines and growth factors are what’s left.

Sanderson, MD, John; Taylor, MD, George, Cellese Regenerative Therapeutics, (2017)

Credit: Sanderson, MD, John; Taylor, MD, George, Cellese Regenerative Therapeutics, (2017)

Adipose (fat) and PRP (platelet rich plasma) conditioned media, on the other hand, are PRO-INFLAMMATORY.  Embryonic foreskin fibroblasts only produce 2-10% of the number of cytokines and growth factors that BM-MSCs produce.  Describing the advantages would fill a textbook and probably require a degree in biogenetics to understand fully. 

A look at existing products on the market demonstrates the variety of stem cell sources being used:

  • TNS by SkinMedica (an Allergan company) – use cultured neonatal foreskin fibroblasts. These produce small quantities of cytokines and growth factors.
  • Bio-Essentials by NeoCutis – use lysed (aborted) fetal fibroblast cells. These cells go through repeated freeze/thaw cycles, contain cell remnants and large particle sizes, contain a lower concentration of cytokines and growth factors than the TNS product.)
  • Lifeline by ISCO – lysed ova; similar to Bio-Essentials there is limited penetration.
  • ReLuma, SFS by Osmosis & Luminesce - Adipose (fat) derived stem cells - produce PRO-INFLAMMATORY cytokines.
  • AnteAGE MD by Cellese – strongly ANTI-INFLAMMATORY cytokines and growth factors obtained from bone marrow of young adults in early 20’s.

Because skin aging is an accumulation of small injuries over time, BM-MSCs are well-suited for use in advanced anti-aging skincare. Stem cells in skincare are among the latest breakthroughs helping address common concerns with aging skin – activation of wound healing and stimulation of collagen synthesis. 

Stem cells work best with growth factors, which signal the stem cells to go to the targeted location and renew collagen, elastin, and epithelial cells.

Growth Factors – “Give Directions”
Discovered in the 1950’s.  Launched in skincare in the 1990s.

Growth factors (a component of stem cells) are naturally occurring substances (proteins or hormones) that affect the division and growth of the body’s cells, stimulating cellular renewal. Growth factors accelerate skin renewal during and after esthetic procedures such as micro-needling, lasers, and peels.  When growth factors are applied topically, the stratum corneum stimulates a repair message that goes into the dermis via a signaling cascade, stimulating fibroblasts to produce collagen and revitalize damaged or aging skin.  Growth factors were first used to treat patients in burn centers.

Growth factors are chains of amino acids, similar to peptides, only bigger in size.  Like peptides, growth factors direct cell behavior by binding to receptors on the cell’s surface and directing it to grow, divide or differentiate.  Also like peptides, there are different types of growth factors that produce varying effects on target cells.  Growth factors are most bio-active when derived from human sources (as opposed to plant sources) since they work with growth factors normally present in the skin.

Fact: the aging process leads to a decrease in growth factors.

Some growth factors used in skincare include Epidermal Growth Factor (EGF) to accelerate healing, Fibroblast Growth Factor (FGF) to stimulate fibroblast production, Insulin-like Growth Factor (IGF) to promote cell growth, Keratinocyte Growth Factor (KGF) to stimulate epithelial cell growth, Platelet-Derived Growth Factor (PDGF) to regulate cell growth and Transforming Growth Factor-Beta (TGF-β) to stimulate collagen secretion. Growth factors are often cocktailed with peptides, hyaluronic acid, antioxidants, and growth factor precursors—stem cells.

Here’s what to look for when exploring formulas that claim to contain growth factors:

Oligopeptides

Sh-Oligopeptide-1 is known as Epidermal Growth Factor (EGF), a synthetic EGF engineered to mimic the structure of human EGF, which is produced in various parts of the body.

Sh-oligopeptide-2 is related to EGF and is also purported to promote cellular reproduction and regeneration.

Polypeptides

Sh-Polypeptide-11 is referred to as Acidic Fibroblast Growth Factor.  This growth factor causes fibroblasts (connective tissue cells that produce collagen) to reproduce and grow. Sh-Polypeptide-1 (aka Basic Fibroblast Growth Factor) does essentially the same thing.

Sh-Polypeptide-9 (Vascular Endothelial Growth Factor) provides nutrients to fibroblasts.  

Finally, Transforming Growth Factor – type Beta 3 (TGF-b3). Recombinant human TGF-β3, first cloned around 1990 and produced in the laboratory, is a polypeptide chain containing 112 amino acids.  Cytokine TGF-b3 is the reason fetal skin heals scar-free (with a very brief inflammatory phase) and adult skin heals with scar tissue, with abundant stiff type I collagen.  TGF-b3 promotes the increase of pliable collagen III.

TGF-b3 is found throughout the body and is required for development before birth (regulates embryogenesis) and cell differentiation throughout life.  In skincare, we are most interested in how TGF-b3 controls wound healing by regulating the movements of epidermal and dermal cells in injured skin, and how they stimulate scar-free healing.

Because they stimulate collagen production and cell regeneration, growth factors may be a worthwhile addition to your anti-aging arsenal if you’re looking to maximize your skin-care regimen.  [Sunscreen, antioxidants, alpha hydroxy acids, and retinols should take precedence, however.]  Studies have shown that using products containing growth factors can minimize the appearance of expression lines and wrinkles, improve the skin’s texture, and provide hydration.  

Conclusion

Now that we’ve broken down the nuances between peptides, stem cells and growth factors, you can understand why and how to look for these ingredients when shopping for skin care products. As we have seen, each of these elements offer unique benefits that often work most effectively when used together, so you’ll want to look for formulas that contain a good amount of these active ingredients in some combination.

BevTip: You can tell a product contains very little of an active ingredient if it appears at the end of a long list of other ingredients.

Professional procedures creating ‘productive’ stress on the skin should include growth factors, stem cells, and peptides to supplement the skin's natural repair system. These ingredients should be applied during and after procedures to help the skin heal optimally.

The bottom line: Adopting a more-the-merrier approach to skin-plumping ingredients is a smart idea, especially as 40 nears.   If you are over 40, it’s never too late to start, you just have to work a little harder to get the same results.  Peptides, stem cells, and growth factors can bolster your existing beauty regimen without inflaming your face. Go for a research-backed formula that suits both your skin and sensibilities.

Where do these products fit into your skincare regimen?  It depends on the formulation.  If the pH of the product is lower (around a 3-4), then feel free to use it along with your daytime vitamin CE Ferulic antioxidant serum and alpha hydroxy acids (glycolic acids) since they will be compatible, and the glycolic acid will act as a great carrier of the peptides and larger size growth factors. Any products that contain niacinamide or retinol (along with the peptides, growth factors or stem cells) or have a higher pH between 5-6, should be used in the evening.  These products are very compatible together and the retinoid will help the larger proteins penetrate better.   

Bev’s recommendations: Below are three examples of products that I like to use at different times because of their pH:

Nutra-lift Rejuvenating Gold Peptides and Growth Factor serum (pH ~ 3-4; 14% peptides & growth factors).  I use this product after CE Ferulic and before my glycolic acid cream.

AnteAGE MD® | Stem Cell & Growth Factors System (pH ~ 5.5-6.0); contains niacinamide as well as plant-based bakuchiol retinoid.  I use this system in the evening before using my prescription strength tretinoin.

Cosmetic Skin Solutions Copper Peptide Serum (pH ~ 5.5-6.0):  I prefer to use this one in the evening for the same reason; although, the formulator says it is stable and can be used effectively with vitamin C antioxidants.

Please let us know if you have any questions. If you would like to discuss your skincare needs in person, please sign up for a Virtual Consultation.

For a printable versionclick here (PDF).

References 

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  1. Wong WT, Sayed N, Cooke JP. Induced pluripotent stem cells: how they will change the practice of cardiovascular medicine. Methodist Debakey Cardiovasc J. 2013 Oct-Dec;9(4):206-9. doi: 10.14797/mdcj-9-4-206. PMID: 24298311; PMCID: PMC3846074.
  1. ten Dijke P, Iwata KK, Goddard C, Pieler C, Canalis E, McCarthy TL, Centrella M. Recombinant transforming growth factor type beta 3: biological activities and receptor-binding properties in isolated bone cells. Mol Cell Biol. 1990 Sep;10(9):4473-9. doi: 1
  1. Sanderson, MD, John; Taylor, MD, George, Cellese Regenerative Therapeutics, (2014), “Improving Aesthetic Outcomes: Physical modalities combined with topical cytokines and growth factors.” 
  1. López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido (2013-06-06). "The Hallmarks of Aging". Cell. 153 (6): 1194-1217. doi:10.1016/j.cell.2013.05.039. ISSN 0092-8674. PMC 3836174. PMID 23746838.
  1. https://www.truthinaging.com/review/what-are-neuropeptides
  1. https://www.wellandgood.com/good-looks/plant-stem-cells-in-skin-care/
  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108505/
  1. https://incidecoder.com/ingredients/sh-polypeptide-1

  2. https://incidecoder.com/ingredients/sh-polypeptide-9
  1. https://incidecoder.com/ingredients/sh-oligopeptide-1
  1. Sanderson, MD, John; Taylor, MD, George, Cellese Regenerative Therapeutics, (2017), “Topical Cytokines & Growth Factors in Anti-Aging and Aesthetic Medical Practice."