Stem Cells

By Dr Jenna Burton / 18 Sep 2017

Dr Jenna Burton examines the role of topical stem cells in medical aesthetics and compares the potency of topical application versus injectable techniques

In the past few decades, stem cells have been harvested to help eradicate arthritic symptoms,1 been used to cure bone marrow deficiencies,2 regenerate breast tissue,3 and have even been used in the cloning of sheep.4 To add to their various and diverse range of uses, they are now been utilised in daily skincare regimes.

Stem cells have a magnitude of purposes. In this article, I shall explore the use of stem cells in skincare and their topical application to identify whether sufficient evidence exists to support their role as antiageing treatments.

What are stem cells?

Stem cells are pluripotent cells – immature cells capable of giving rise to several different cell types – and have the ability to develop into every type of cell within the body. For example, a three-to-five-day-old blastocyst in a mother’s womb initially begins life as a cluster of stem cells. This cluster of cells holds the remarkable ability to produce the skin, heart, lungs and every single cell within the human body; despite the vast diversity in purpose, function and biological anatomy.5

By definition, stem cells have four main characteristics, they:5

  • Mobilise during angiogenesis
  • Differentiate into specialised cell types
  • Proliferate and regenerate
  • Release immune regulators and growth factors

There are two main forms of stem cells. Those which are embryonic in nature; embryonic stem cells, and those which are induced into pluripotency, in other words, reverted back to their more immature state with the capability of giving rise to several different cell types; somatic stem cells.

Embryonic stem cells

The cultivation of human embryonic stem cells was first achieved following research with unused IVF products and aborted foetuses in 1998;6 this was 17 years after a study that obtained stem cells derived from mice.7 In 2006, it was discovered that it was possible to reprogramme specialised adult cells,8 restoring their stem cell quality and hence restoring their ability to develop into any type of cell within the body. This was part of a study conducted by scientists de Wert and Mummery, who converted mice fibroblasts and tail tip fibroblasts into embryonic stem cells using a series of transcription factors. This was a major breakthrough that removed the ethical debate of utilising embryonic stem cells, which remains controversial in nature secondary to their derivation from early embryos.9 

The removal of the ethics debate gives rise to the revolution of much of our medical practice by vastly increasing our access to stem cells and allowing for further research opportunities surrounding their use. A major benefit of all stem cells is their ability to restore and repair, often being referred to as an ‘internal repair system’.5 This occurs both through the production of new tissue cells and through their release of immune regulators and growth factors stimulating nearby cell division, a function that has proved particularly beneficial when injecting stem cells into joints1 and when using them as graft tissue.10

Somatic stem cells

There are three main sources of stem cells other than those extracted from embryos:

1. Blood and bone marrow

Blood from our circulatory system and bone marrow extracted from the bone can be given back to the same person to replenish their haematopoietic stem cells; this is useful for leukaemia patients.11 The practice has also been used in cosmetic procedures such as platelet rich plasma (PRP) treatments, when useful compounds such as growth factors are injected back in to the skin from plasma taken from brachial veins.12

2. Blood cells from a baby’s umbilical cord

Blood can be stored at birth and infused back into the individual at a later stage in the form of red and white blood cells and platelets. This would be done in case the individual needed a transfusion due to ill health at a later stage. Currently this service is only carried out by six NHS hospital facilities.13 The use of umbilical cord blood cells is currently under much investigation for treating brain conditions14 and metabolic complaints such as insulin-dependent diabetes mellitus,15 though this is still at the stage of preliminary research.

3. Adipose tissue

Usually taken from the abdomen and buttocks, adipose tissue is most extensively used within orthopaedic and cosmetic procedures. Cosmetic procedures include fat grafting for the face and breast, along with injections into scar tissue to promote healing. As a source of mesenchymal stem cells, adipose tissue can differentiate into many types of cells such as fat, muscle, bone, cartilage, nerve cells and cells found within the epidermal and dermal layers of the skin.16 Mesenchymal stem cells are an example of tissue or ‘adult’ stem cells. They are multipotent, meaning they can produce more than one type of specialised cell within the body.

Adipose cells are most commonly used when administering autologous stem cells to a recipient for the purposes of antiageing. However, many alternatives have been explored, including the application of plant stem cells17 and animal embryonic stem cells.18

Fat grafting

Fat grafting, the transfer of fatty tissue containing stem cells, has been around for decades before the discovery of stem cell use. Initially unaware of the mesenchymal stem cell benefits, fat grafting made an appearance as early as 1893 for use of filling soft tissue defects.19 Not only was this a longer-lasting alternative to collagen and hyaluronic acid, it was also autologous, reducing the risk of immune complications.19

Prior to the use of competent stem cell transfer in cosmetics, orthopaedic surgeons had been utilising its practice with confidence for conditions such as arthritis, tendinopathies and repair of meniscal injury. 

Although clinical research has remained limited, cell-based techniques involving the injection of mesenchymal stem cells into injured joints have shown improved cartilage repair, repair of meniscal injury and reduced inflammation within arthritic joints, and these are used extensively within every day practice.20 However, additional studies with a lengthier follow up are required to further evaluate these findings in a longer-term environment.

Fathke et al. reported that distant bone marrow-derived stem cells contributed to the reconstitution of the dermal fibroblast population in cutaneous wounds

Orthopaedic surgeon, Dr Cecilia Pascual-Garrido, conducted a small study on eight patients with patellar tendinopathies21 – an overuse injury affecting the knee. These patients were injected with autologous mesenchymal cells, and all reported significant improvements in mid-term follow ups at two to five years, a result which reflects the antiageing and repair properties of the stem cells used.

With the added gratification of removing storage of adipose tissue, along with a reported, ‘natural and soft’ appearance and improved appearance of local scar tissue, it was not long before fat grafting was also being used for breast reconstruction in 1895, for women who had undergone surgical mastectomy. 

Not only did the newly reconstructed breasts display natural, female curves and movement, but the overlying skin tone and scar tissues were much improved. This was later attributed to stem cells within the adipose tissue and prompted exploration for stem cells targeted directly at the skin itself.19

Stem cells and the skin

Stem cells were first used for the skin when investigating methods for improved wound healing. It is well known that during the inflammatory phase of wound healing, blood-borne immunocompetent cells invade the wound area, which are suggested to be derived from bone marrow. As severe injury increases the level of stem cells in the blood,22 it is of no surprise that during times of more minor local stress to the skin, stem cells are called upon for the purposes of healing.

This was indicated by Badiavas et al.23 who inflicted mice with skin wounds. Prior to the wound, green fluorescent protein (GFP) had been ‘tagged’ into the bone marrow of the mice population. They later found GFP-labeled cells in the wound site. Similarly, Fathke et al. reported that distant bone marrow-derived stem cells contributed to the reconstitution of the dermal fibroblast population in cutaneous wounds.24 These findings suggest an important contribution of stem cells within the wound healing process.

Bone marrow-derived mesenchymal stem cells do appear to produce higher quantities of collagen and growth factors than those extracted from adipose tissue

Mesenchymal stem cells derived from more readily available sources such as adipose tissue, along with the less readily available sources such as bone marrow, are capable of self-renewing and differentiating into various tissues with little concern over immune rejection.25 

Such tissues include those found in the epidermis, dermis and hypodermis and have received copious amounts of attention regarding their use in the field of dermatology and cosmetics, along with wound healing, diabetic skin ulcers and with burn victims.26 However, bone marrow-derived mesenchymal stem cells do appear to produce higher quantities of collagen and growth factors than those extracted from adipose tissue,27 hence the volume of stem cells required for healing should be considered.

Cosmeceuticals

Although stem cells appear to offer antiageing and rejuvenating properties when injected from bone marrow and adipose tissue, is this supported when applied topically? With popularity surrounding the recent release of antiageing ‘stem cell serums’ and cosmeceuticals, does the science support the claims? 

We have discussed the antiageing repair properties of stem cells, yet many dermatologists claim that when topically applied, their benefits are significantly reduced. Dr Erin Gilbert, assistant professor of dermatology at SUNY Downstate Medical Centre, US, spoke publically at the Cosmetic Surgery Forum in Las Vegas stating that “Stem cells are a natural ingredient, and within topical products, clones of stems are cultivated resulting in a less effective outcome.”28

Gilbert said, “The downside of products containing intact stem cells is that they have no real biologic utility, as they are DOA (dead on arrival) in the absence of a supporting biological environment. Products containing whole-tissue homogenates are likely to be more effective antiageing treatments because they offer a broader range of beneficial substances, such as autologous fat tissue injections potentially used as fillers for defects of the face, or to fill in deep sunken scars.”

Research published in the Journal of Dermatology in 2007 demonstrated the benefit of a novel skin cream containing a mixture of growth factors and cytokines, which was obtained through a biotechnology process using cultured human foetal fibroblasts

However, she added that stem cell-derived growth factors, that stimulate growth factors and cytokines, are of ‘strong interest’ to researchers in the aesthetics specialty, suggesting that there remains potential for development, despite her current concerns.

Dr Roy G Geronemus, chairman of the board of the New York Stem Cell Foundation – the largest stem cell research programme in the US – agrees with Dr Gilbert. He said, “It makes me sad when I see a dermatologist promoting stem cell products, because we need to be the expert resource on skincare that our patients can trust.”

Despite this, research published in the Journal of Dermatology in 2007 demonstrated the benefit of a novel skin cream containing a mixture of growth factors and cytokines, which was obtained through a biotechnology process using cultured human foetal fibroblasts. 

The skin surface topography was analysed by 3D in vivo by an optical skin imaging device. It was revealed that following two months of application twice-daily, there was a 10-18% reduction in roughness.29

Notwithstanding the dermatological debate, there is little argument that suggestive studies and patient feedback implies satisfaction for the use of stem cell serums and cosmeceuticals, along with the growth factors that they contain. Below are some examples of studies demonstrating positive results:

  • The Mibelle AG Biochemistry company, which is a specialist cosmetic company providing research teams for cosmetic advances, carried out clinical tests for stem cell serums. The study, on 20 female participants aged 37-64 years, lasted four weeks. Depth of wrinkles was measured using the PRIMOS system – an optical device for 3D skin surface display, on the test start and after two and four weeks from there. The research indicated that the wrinkles became ‘shallow’ by 8% after two weeks and by 15% after one month.30
  • Drugs of Dermatology (2012) published a study on the effects of applying growth factors contained in stem cell serums. The three month, open-label, single centre study was conducted to determine whether a uniquely derived serum containing barley bioengineered, human-like epidermal growth factor protein could improve visible signs of photodamage and ageing in facial skin. The study was conducted on 29 female patients, aged 39-75 years, with mild to severe, fine and course rhytids, photodamage, and pigmentation. Subjects applied the serum protocol twice-daily for three months, in addition to the use of a basic sunscreen and facial cleanser. In-person clinical evaluations and subject self-assessment questionnaires were used. Clinical evaluations exhibited statistically significant improvement in the appearance of fine lines and rhytids, skin texture, pore size, and various dyschromatic conditions apparent within the first month of use, and continuing improvement trends for the duration of the study.31
  • Regenica gel, which contains growth factors, was tested for its efficacy in healing skin after laser resurfacing. The split-face clinical evaluation included 42 subjects undergoing combination ablative and non-ablative laser procedures. Histopathology indicated reduced inflammation in biopsies from treated skin compared to untreated skin.32

Conclusion

With their ability for harvesting, small concerns over immune reactions and the potential for growing incredibly useful by-products including growth factors, it seems likely that the use of stem cells will continue to expand and form the foundation of much future research, both within cosmetics and within mainstream medicine. It has been indicated through clinical studies that stem cells are beneficial for the skin, within wound healing, skin grafting and when injecting blood and adipose tissue beneath the skin’s surface. They assist with scar healing, and can promote suppleness and improved pigmentation to the skin surface, with results outlasting collagen and hyaluronic acid substitutes.16,18,19

As well as this, they are natural. However, it appears that despite the media boom surrounding stem cell topical treatments, further research is needed on a long-term human study basis before we can report their use with confidence. 

References

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