Over the past few decades, there has been a profound improvement in our understanding of stem cell biology and its connection to hair growth. Along with promising innovations in the exploration of new regenerative therapies, more revelations have been made concerning the stem cells that are found within hair follicles. This article will discuss the significant developments in our understanding of hair stem cells and the state-of-the-art research techniques for reviving dormant hair follicles to produce colored hairs. Stem cells and hair regrowth are transforming hair restoration by naturally revitalizing hair follicles.
Exploring Hair Regeneration Using Plucked Hair Follicle Cells
- Early studies found that plucked hair follicles, when grafted back onto nude mice skin, could reinitiate hair cycling and growth. More recent work has built upon these observations by cultivating hair follicle stem and progenitor cells isolated from plucked follicles under conditions optimized to selectively expand keratin 15-positive bulge stem cells while retaining their inductive signaling capabilities.
- When these expanded cell populations are transplanted back onto nude mouse skin, de novo hair follicles form recapitulating the normal hair induction sequence including down growth and hair fiber production.
- Researchers are working to translate these techniques through testing on non-human primate models and exploring physiological improvement of expanded cell transplant outcomes through combinatorial delivery of signaling molecules and extracellular matrices.
Therapeutic Potential of Induced Pluripotent Stem Cells
- These induced pluripotent stem (iPS) cells can theoretically redifferentiate into any adult cell type, including hair-inducing populations.
- In early investigations of this technology, mouse fibroblasts were reprogrammed to an iPS state using retrovirus expression of key regenerative transcription factors and subsequently coaxed toward dermal papilla– and epithelial bulge stem cell-like lineages using growth factor cocktails.
- When transplanted into nude mice, these iPS cell-derived populations reconstituted de novo hair follicles and follicular cycling.
- Researchers are now working to streamline reprogramming and differentiation techniques to allow for scalable production of human hair-inducing populations for therapeutic use.
- Such iPS cell technology holds promise for developing “bottomless” sources of transplantable cell types applicable to alopecia disorders where few endogenous follicles remain. However, challenges remain in demonstrating the safety and efficacy of this approach before clinical translation.
Targeting Wnt Signalling to Reawaken Dormant Follicles
- Alongside regenerating hair follicles from stem cells, regenerative strategies aim to reactivate existing but dormant follicles in bald scalp skin.
- Several signaling pathways are recognized to play key inductive roles during follicle morphogenesis and cycling, with the Wnt family of ligands emerging as primary drivers.
- Investigations have shown that culturing human dermal papilla cells in the presence of specific Wnt proteins leads to enhanced production of growth factors able to trigger surrounding epithelial cells to proliferate and form hair germs-like organoids in vitro. Building on this, preclinical studies have tested whether stabilizing Want signaling in dormant follicles using small molecule pathway activators could stimulate them to re-enter growth cycles in vivo.
- Local delivery of either Wnt proteins or compounds inhibiting Wnt inhibitors triggered the reawakening of telogen follicles in animal models, eliciting waves of new hair fibre production over a matter of weeks.
- While toxicity and targeting challenges remain for Wnt-based topical therapies, insights gained here support further development of ligands and pathway regulators for stimulating quiescent follicles in alopecia conditions.
- Multi-target approaches activating not just Want but also other critical hair induction signaling networks may provide complementary strategies.
Emerging Role of Follicular Macrophages
- Adding to our knowledge of the biology driving hair follicle regeneration, immunological factors have emerged as playing equally vital inductive/inhibitory roles.
- Recently, specific subsets of macrophages residing within the hair follicle microenvironment have been identified to be indispensable for maintaining stem cell properties and inductive crosstalk signaling needed for follicular regeneration.
- Studies comparing normal balding, and wound healing models have revealed that progressive disappearance of these distinct CD163+ macrophages from the lower follicle correlates with impaired hair cycling ability.
- Depletion of these follicular macrophages impairs the Wnt/β-catenin pathway in dermal papilla cells, compromising signaling networks driving stem cell-fueled growth. Conversely, experiments restoring macrophage numbers in balding skin using growth factor injections restored Want signalling activity and initiated new hair germ formations from dormant follicles.
- These results reveal an unexpected core immunological component to follicle regenerative biology, introducing an orthogonal way to therapeutically control hair follicle stem cell fate by manipulating their follicular macrophage partners.
How Stem Cells May Be Used to Treat Human Hair Loss
Based on the encouraging preclinical results to date, here is how stem cells could potentially be used clinically:
- Minimally-invasive injections of MSCs or iPSC-derived cells like dermal papilla progenitors directly into balding scalp areas. Repeated injections may improve results.
- Hair follicle cell “sheet transplantations” where sheets of keratinocytes and dermal papilla cells derived fromiPSCs or MSCs are transplanted rather than individual cells for better structure development.
- Combination therapies using stem cells along with existing treatments like minoxidil, finasteride, or PRP/platelet-rich plasma injections for a synergistic effect. Stem cells may augment their mechanism of action.
- “Inject-and-go” approach where a single injection of targeted MSCs loaded in appropriate scaffolds is designed to locally differentiate and restore hair growth sustaining long-term results.
- Addressing potential safety concerns from transplanting foreign stem cells is also important. Further optimizing stem cell culturing, controlling differentiation, and ensuring no teratoma or tumor formation will be critical before human use. With more research, stem cell therapy could greatly improve current hair loss treatments.
Conclusion
While still in the preliminary stages of research, stem cells hold tremendous potential as a regenerative medicine approach for treating hair loss conditions. By understanding how they encourage new hair follicle growth at a molecular level, scientists are working to develop minimally invasive stem cell therapies. With further refinement, this could revolutionize treatment options and provide an attractive non-surgical solution for millions of people suffering from hair loss. Continued research exploring the optimal cell sources, administration methods, and combination therapies with traditional drugs holds promise to realize stem cells’ potential for spurring new hair growth.
