Exosomes are lipid bilayer vesicles, 30–200 nm in diameter, that are produced by cells and play essential roles in cell–cell communication. Exosomes have been studied in several medical fields including dermatology. Hair loss, a major disorder that affects people and sometimes causes mental stress, urgently requires more effective treatment. Because the growth and cycling of hair follicles are governed by interactions between hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs), a better understanding of the mechanisms responsible for hair growth and cycling through exosomes may provide new insights into novel treatments for hair loss. In this review, we focused on the comprehensive knowledge and recent studies on exosomes in the field of hair development and regeneration. We classified exosomes of several cellular origins for the treatment of hair loss. Exosomes and their components, such as microRNAs, are promising drugs for effective hair loss treatment.
Exosomes and extracellular vesicles
Extracellular vesicles (EVs) are lipid bilayer vesicles, which can be secreted by most types of cells, including bacteria, fungi, plant cells, parasites, and animal cells, indicating a conservative evolution (7). EVs include exosomes, microvesicles and apoptotic bodies. In terms of size, the diameter of exosomes ranges from 30 to 200 nm; the size of microvesicles is 100–1000 nm; the largest is the apoptotic body, which has a diameter from 500 to 2000 nm (8). The process of exosome formation is
Isolation and characterization of exosomes
Currently, there are several exosome isolation methods, including ultracentrifugation, ultrafiltration, polymer precipitation, size-exclusion chromatography, immunoaffinity capture, and microfluidics-based techniques (11). According to a review (12) in which 126 articles were counted to analyze exosome isolation methods, ultracentrifugation is the most widely used method to isolate exosomes from the culture media of mesenchymal stem cells (MSCs), accounting for approximately 54 %, followed by
Hair follicle development as well as hair growth and maintenance
As shown in Fig. 2A, a series of signals between epithelial and mesenchymal cells lead to changes in both cell populations that eventually differentiate into mature hair follicles. The crosstalk between the two cell types may be largely governed by exosome-mediated transport, which will be discuss later. The emergence of a first dermal signal in the dermis results in the formation of thickenings of some parts of the epidermis, called placodes. Signals from the epithelial cells of the placode
Hair loss treatment in cell therapy and the use of exosomes
As early as 1997, transplanted cells (containing DPCs) could be used for hair regeneration in animal models for the treatment of hair loss (33). When freshly prepared hair buds or primary mouse keratinocytes were mixed with active rat DPCs and transplanted into nude mice, hair follicles formed in the reconstructed skin, whereas no hair follicles formed in the reconstructed skin when hair buds or keratinocytes were mixed with dermal fibroblasts. The hair-inducing activity of DPCs was retained;
DPC-derived exosomes
In the current exosome studies in the field of hair, exosomes derived from DPCs are widely used in hair studies. DPCs are mesenchymal cells with adult stem cell properties that regulate hair follicle development by interacting with epithelial cells and play an essential role in the hair growth cycle (53).
In a study by Zhou et al. (46), human two dimensional cultured DPC-Exos were injected into the dorsal skin of mice in the telogen and anagen phases. The results showed that hair follicles
Current limitation of exosomes in clinical applications
The use of exosomes in various medical fields has attracted increasing interest from researchers; however, there are still limitations to their clinical application. There is a lack of a uniform gold standard for the origin, isolation, purification, identification, and storage; furthermore, clinical applications require a high degree of controllability and standardization (67). The precise quantification of exosomes and effective concentration methods are also of interest because ensuring that
Conclusion and perspectives
Exosomes have been widely studied owing to their long shelf life, simple storage conditions, long intracellular communication distances, and low risk of immune responses, making them superior to direct cell therapy (69). Here, we present the mechanisms and related studies of exosomes in the promotion of hair growth and regeneration. Because of their paracrine role, exosomes are involved in a variety of physiological and pathological processes in hair follicles. As intercellular messengers
