Why Targeting Keratinocytes May Outshine Traditional Dermal Papilla-Based Therapies

Recent research from South Korea has highlighted the significant role of hair follicle keratinocytes in hair growth and loss, suggesting that treatments targeting these cells may be more effective than those focusing solely on dermal papilla cells.

Keratinocytes, the predominant cell type in the outer root sheath (ORS) of hair follicles, are crucial for hair formation and cycling.

Studies have shown that factors inducing hair loss, such as DKK-1 and TGF-β1, can cause apoptosis (programmed cell death) in ORS keratinocytes, leading to decreased cell viability and hair loss.

Conversely, interventions that inhibit this apoptosis in ORS keratinocytes have been found to promote hair growth.

For instance, a study demonstrated that inaudible sound treatment inhibited DKK-1 and TGF-β1-mediated apoptosis in ORS keratinocytes, thereby promoting their survival and potentially supporting hair growth.

Additionally, research involving the intradermal injection of human hair-derived keratin has shown promotion of hair follicle formation and subsequent hair growth in a mouse model, further emphasizing the importance of keratinocytes in hair regeneration.

These findings suggest that therapeutic strategies aimed at protecting and stimulating hair follicle keratinocytes could offer promising alternatives or enhancements to existing treatments that primarily target dermal papilla cells.

By focusing on the health and function of keratinocytes, it may be possible to develop more effective interventions for hair loss conditions.

The emerging research from South Korea underscores the pivotal role of hair follicle keratinocytes in regulating hair growth and hair loss. Traditionally, many hair loss treatments have been centred around dermal papilla (DP) cells due to their role in signalling hair follicle growth cycles. However, this new focus on keratinocytes—cells that form the outer root sheath (ORS) and are crucial for the structural integrity and function of hair follicles—opens new avenues for therapeutic strategies.

Key Findings and Insights:

1. Keratinocytes’ Role in Hair Growth and Structure:

   • Keratinocytes contribute to the formation and cycling of hair by maintaining the structure and support of the hair follicle.
   • They are essential in responding to growth signals from DP cells and maintaining a healthy hair growth environment.

2. Apoptosis and Hair Loss:

   • Factors like DKK-1 (Dickkopf-1) and TGF-β1 (Transforming Growth Factor Beta 1) are known to induce apoptosis (programmed cell death) in ORS keratinocytes.
   • This apoptosis disrupts hair follicle function, leading to weakened hair follicles and subsequent hair loss.

3. Protective Mechanisms and Therapeutic Approaches:

   • Inaudible Sound Therapy: Research shows that specific inaudible sound waves can inhibit DKK-1 and TGF-β1, protecting keratinocytes from apoptosis. This promotes cell survival and enhances the conditions necessary for hair growth.
   • Keratin-Derived Treatments: Intradermal injections of human hair-derived keratin have been shown to promote the formation of new hair follicles in experimental models, suggesting that external keratin supplementation may support keratinocyte function and hair regeneration.

4. Implications for Hair Loss Treatments:

   • Shift in Focus: Moving beyond DP-cell-centric treatments, strategies targeting keratinocyte health and survival could complement or even surpass the effectiveness of current approaches.
   • Combination Therapies: Treatments that synergize DP cell stimulation with keratinocyte-focused therapies could provide comprehensive benefits by addressing both the signalling and structural aspects of hair growth.

5. Potential Applications:

   • Topical Formulations: Products aimed at delivering protective agents directly to keratinocytes in the ORS.
   • Injections or Micro needling: Utilizing bioactive compounds or keratin-based materials to enhance keratinocyte resilience and promote follicle health.
   • Personalized Medicine: Developing specific interventions for individuals based on the underlying cause of their hair loss and the state of their keratinocytes.

Broader Context:

This research challenges the prevailing paradigm in hair biology and highlights the complexity of hair follicle dynamics. By acknowledging keratinocytes' direct involvement in hair follicle viability, scientists can develop treatments that are not only reactive but also preventive, targeting early signs of keratinocyte damage before significant hair loss occurs.

In conclusion, keratinocyte-centred approaches to hair loss represent a promising frontier in dermatology, offering hope for more effective and targeted therapies for a condition that affects millions globally.