Androgenic hair loss in women is a common condition that significantly affects quality of life. Various treatment modalities have been explored, with microneedling of the scalp combined with the application of purified enriched animal-derived exosome therapy emerging as a promising approach.  

Exosome extracellular vesicles’ mechanism of action involves dermal papilla proliferation, growth factor upregulation, suppression of proinflammatory cytokines and Wnt/β-catenin signalling pathway, with emerging evidence indicating that they can increase hair density, thickness and the anagen to telogen ratio.1,2,3   

ALLSKIN|MED HAIR (Cantabria Labs, Spain), a range of dermatological hair and scalp care professional-use products, utilise Wharton Gel Complex® – a highly purified bioactive hydrogel of natural glycosaminoglycans and growth factors, which are natural components of the hair follicle dermal papilla and whose expression is associated with the hair growth cycle.4-8  

Wharton Gel Complex has been reported to help promote and support the sustained growth of human hair follicles by activating the Wnt/β-catenin signalling pathway, along with upregulating TGFβ2 and activating the hair follicle stem cell niche and to increase hair thickness, density and strength.9,10   

Exosomes and Wharton’s Gel Complex are different bioactive technologies that potentially have complementary mechanisms of action. Based on this rationale I have evaluated the use, in my medical aesthetic practice, of a combined regimen of microneedling of the scalp with the application of exosomes and ALLSKIN|MED HAIR Booster Vial (1.5% Wharton’s Gel Complex in sterile saline), along with the home use of the ALLSKIN|MED HAIR Lotion (1.0% Wharton’s Gel Complex with caffeine and melatonin) in female patients with female pattern hair loss (or androgenic alopecia).  

This case series reports on the tolerability and efficacy observed in five female patients diagnosed with androgenic alopecia treated with this protocol.  

Introduction and methodology 

This is a small case series of five patients who attended our clinic; they had all expressed concern about and exhibited a degree of hair thinning without an underlying reversible physiological cause. The likely diagnosis in all these cases was androgenic hair loss, with all patients reporting a degree of widening of their central parting line or increased visibility of the scalp in general.  

Understanding Female Pattern Hair Loss 

Androgenic hair loss (AGA) in women, also called female pattern hair loss (FPHL), is a common condition characterised by gradual thinning of hair, especially at the crown and top of the scalp, while maintaining the frontal hairline. It is influenced by genetic predisposition and hormonal factors, particularly androgens like dihydrotestosterone (DHT).17-19  

Key features of Female Pattern Hair Loss (FPHL) include:  

1. Gradual thinning of hair mainly at the central scalp. 

1. Widening of the part line due to hair miniaturisation. 

1. No complete baldness, unlike male pattern baldness. 

1. Increased hair shedding in some cases. 

1. Preserved frontal hairline in most women. 

Causes:

• Genetics: Family history plays a key role. 

• Hormonal changes: DHT sensitivity can lead to miniaturisation of hair follicles. 

• Ageing: Often starts after menopause due to declining oestrogen levels. 

• Medical conditions: Conditions like polycystic ovary syndrome (PCOS) can contribute. 

Image from: Ludwig E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. British Journal of Dermatology (1977) 97) 247.20 

Treatment rationale 

Exosomes 

Exosomes are nanosized extracellular vesicles (30-150 nm) secreted by various cell types, and stem cells, including mesenchymal stem cells (MSCs). They play a pivotal role in intercellular communication by transporting proteins, lipids, and nucleic acids, including mRNAs, thereby influencing numerous physiological processes such as tissue regeneration, immune modulation, and angiogenesis.21  

Clinically, exosomes are primarily derived from cultured MSCs. The isolation and purification processes are critical to ensure the safety and efficacy of exosome-based therapies. Standardisation and scalability remain challenges in the widespread clinical application of exosomes.22 Exosomes released from human MSCs have been shown to facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis.23  

We started evaluating E50 Exosomes (STEMON Co. Ltd, Korea) in our medical aesthetic practice, as they are reported to be purified, enriched, and standardised exosomes using a proprietary process known as Entr technology. E50 hair exosomes are collected from salmon testes cells and then cultivated in embryonic stem cell media. The use of salmon cells and the process are claimed to ensure that E50 exosomes have low levels of free radicals and impurities.16  

There is emerging evidence that exosomes derived from MSCs or stem-like cells can modify the pathogenic processes of androgenetic alopecia (AGA) and that exosome treatments increase hair density, thickness, and anagen-to-telogen ratio in animal and early human models of hair loss. The mechanisms of action reported are summarised below:1-3  

• The promotion of dermal papilla cell activity, proliferation, and survival.  

• Upregulating growth factors (VEGF, IGF-1, KGF) essential for hair follicle regeneration. 

• Suppressing pro-inflammatory cytokines (e.g., TNF-α, IL-6) linked to perifollicular inflammation.  

• Reactivation of the Wnt/β-catenin pathway, which is central to initiating and maintaining the anagen phase. 

Wharton Gel Complex 

Wharton Gel Complex (Cantabria Labs, Spain) is a patented bioactive hydrogel of natural glycosaminoglycans (high and low molecular weight hyaluronic acid (HA), sulfated glycosaminoglycans, chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), heparan sulfate (HS)) and growth factors (TGF-β, IGF-I, FGF 1 and 2).  

It has been demonstrated to provide an extracellular matrix substitute that can recruit cells and create an environment that stimulates their natural bioactivity, enabling them to survive and proliferate.9 It is also known that human hair follicle dermal papilla and hair bulb contain high amounts of GAGs (HA, CS, DS, KS, HS) and their associated proteoglycans (sulphated GAGs attached to core proteins).23 

Cyclical expression of GAGs and proteoglycans has been reported during the hair growth cycle and is believed to be important to the maintaining the normal growth phase.24-27 It has been shown to activate the Wnt/β-catenin pathway, upregulate TGFβ2 and FGF10, and to activate the proliferation of the stem cell niche in the hair bulb.9 

In clinical evaluations of patients with AGA, Wharton Gel Complex has been demonstrated to significantly increase hair thickness and density and to reduce hair loss (as measured by the pull test).10,11  

We are utilising this ingredient in our clinical practice in the ALLSKIN|MED HAIR booster vial (1.5% Wharton’s Gel Complex in sterile saline) and the home-use lotion (1.0% Wharton’s Gel Complex with caffeine and melatonin). The range also includes an exfoliating shampoo and an oral supplement. 

Microneedling is a well-established, minimally invasive procedure routinely used in skin rejuvenation and scalp and hair regeneration, stimulating tissue repair and assisting with the percutaneous absorption of topical products.29-30  

The combination approach  

E50 exosomes and ALLSKIN|MED HAIR booster, containing Wharton Gel Complex, are different technologies, for which there is scientific and clinical evidence that enables them to be considered substitutes and stimulators of natural processes and substrates that occur in the hair bulb, follicle and hair growth cycle. There is a reasonable scientific rationale that their combined use, with microneedling of the scalp as an in-clinic treatment procedure, can provide a complementary and potentially synergistic effect in treating hair thinning and loss in patients with AGA.  

For this reason, we have initiated this combination as a treatment option for patients with female pattern hair loss. We also support the patient with an ALLSKIN|MED HAIR home-use regimen, which includes a scalp lotion containing Wharton Gel Complex and the evidence-based ingredients caffeine and melatonin, a shampoo, and a supplement featuring evidence-based ingredients that can help enhance scalp and hair health. 

The treatment protocol and outcome evaluation 

1. In-Clinic Treatments: Patients received four microneedling sessions of the scalp at four-week intervals, during which E50 exosomes were administered into the scalp along with the ALLSKIN|MED HAIR Booster. 

1. At-Home Care: Patients were instructed to use the home-use ALLSKIN|MED HAIR Lotion, Exfoliating Shampoo and oral supplement Capsules consistently between sessions. 

1. Evaluation: Standardised scalp photographs were taken at baseline and at the fourth treatment session to assess changes in hair density and scalp health. Patients were also asked to complete a feedback questionnaire designed to gain insight into the tolerability of the treatment and to gain their opinion on the treatment outcome, and to assess overall satisfaction. 

Results 

Clinical evaluation 

The photographs demonstrate positive clinical outcomes in all patients. On assessment at the fourth follow-up appointment, there is evidence of improved hair density in the treated regions. Using the modified Global Photographic Assessment (MGPA) 7 scale, objective assessment shows an improvement in each of the patients, with clear evidence of improvement in hair growth. 

From photographic changes, patients 1, 2, 3 and 5 have MGPA scores of 6/7, classified as moderate to significant improvement, and patient 4 has an MGPA score of 4/5, classified as no change to slight improvement. Scalp assessment was not specifically formally documented at the time of final assessment, but feedback from patients was overwhelmingly positive.  

Patient evaluation 

All five patients found the treatment comfortable and the home-care products easy to use. Four of the patients at the time of the fourth treatment said they would recommend the treatment to others, while the fifth stated it was too soon to tell how good the results would be and that she would like to wait and see before deciding whether she was satisfied and if she would recommend it to others.  

All five patients liked the at-home treatments, especially the ALLSKIN |MED HAIR shampoo, stating that it was easy to use and made their hair feel nice. Several mentioned that the oral capsules have also had a beneficial effect on nail growth.  

Discussion 

The results we have observed, along with the patient feedback reported in these case studies, demonstrate that the combination treatment protocol can deliver improved hair thickness and density, as well as patient satisfaction and an improvement in the cosmetic feel of the hair.  

Importantly, the tolerability of the combination treatment protocol has been excellent with no adverse effects reported. These outcomes support further use and evaluation of this combination treatment protocol. However, case studies of this nature cannot provide evidence as to whether the combination provides a clinically significant synergistic effect.  

Conclusion  

A combination treatment protocol in five patients with female pattern hair loss consisting of four in-clinic microneedling sessions, along with the application of E50 Exosomes and ALLSKIN|MED HAIR Booster (Wharton Gel Complex 1.5% in saline) at four-week intervals, complemented by the at-home use of ALLSKIN|MED HAIR Lotion (Wharton Gel Complex 1.0%, caffeine, melatonin) and a supporting shampoo and oral supplement capsule, delivered an observable improvement in hair thickness and density in the five reported cases. 

Four of the five patients would recommend the treatment at the time of the fourth treatment, and improvements in the cosmetic feel of the hair were reported. Controlled clinical studies with sufficiently large sample sizes and longer follow-up periods are needed to validate these findings, establish standardised treatment protocols and determine if the combination protocols can deliver proven synergistic results.