Abstract

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are cell-derived membranous structures that were originally catalogued as a way of releasing cellular waste products. Since the discovery of their function in intercellular communication as carriers of proteins, lipids, and DNA and RNA molecules, numerous therapeutic approaches have focused on the use of EVs, in part because of their minimized risk compared to cell-based therapies. The skin is the organ with the largest surface in the body. Besides the importance of its body barrier function, much attention has been paid to the skin in regenerative medicine because of its cosmetic aspect, which is closely related to disorders affecting pigmentation and the presence or absence of hair follicles. The use of exosomes in therapeutic approaches for cutaneous wound healing has been reported and is briefly reviewed here. However, less attention has been paid to emerging interest in the potential capacity of EVs as modulators of hair follicle dynamics. Hair follicles are skin appendices that mainly comprise an epidermal and a mesenchymal component, with the former including a major reservoir of epithelial stem cells but also melanocytes and other cell types. Hair follicles continuously cycle, undergoing consecutive phases of resting, growing, and regression. Many biomolecules carried by EVs have been involved in the control of the hair follicle cycle and stem cell function. Thus, investigating the role of either naturally produced or therapeutically delivered EVs as signaling vehicles potentially involved in skin homeostasis and hair cycling may be an important step in the attempt to design future strategies towards the efficient treatment of several skin disorders.

Highlights

  • The skin is the largest organ in the body in terms of extension (1.5–2 m2 in humans) and comprises around 16% of total bodyweight [1]

  • An induction in β-catenin and Sonic hedgehog (Shh) levels was detected in treated skin, as well as in epithelial hair follicle outer root sheath cells isolated from human scalps and cultured with dermal papilla (DP) exosomes. These results consistently revealed the participation of Wnt/β-catenin and Shh pathways in the molecular mechanisms driving hair growth in response to exosomes

  • These observations suggest that since Extracellular vesicles (EVs) cargo has the potential to target a wide range of molecular processes and recipient cells, EVs emerge as both natural mediators potentially participating in the control of the hair cycle and promising delivery vehicles for the improvement of skin and hair regeneration

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Summary

Introduction

The skin is the largest organ in the body in terms of extension (1.5–2 m2 in humans) and comprises around 16% of total bodyweight [1]. Extracellular vesicles (EVs) comprise a heterogeneous variety of membrane-enclosed structures in termEsxtorfacseilzlue,lamr veecshiacnleism(EsVos)f cboimogperniseesias,hectoemropgoesnietioouns, vcaarrigeoty, oafnmd efmunbcratinoen-se.nclTohsedy sctorunctatuinres in terms of size, mechanisms of biogenesis, composition, cargo, and functions They contain transmembrane proteins and enclose components derived from the donor cell that may include. Despite the increasing consensus about EV classification, it is hard to distinguish them once they reach the extracellular space Their interaction with recipient cells can occur in different ways: ligand-receptor interaction; internalization by clathrin-dependent endocytosis, caveolin-mediated uptake, macropinocytosis, or phagocytosis mediated by specific receptors; and direct fusion with the plasmatic membrane of the recipient cell, thereby involving the release of EV content in the cytoplasm of the recipient cell [16]. These processes can affect a number of key cellular signaling pathways that modulate essential cellular processes, such as proliferation, differentiation, migration, and cell death

Use of Extracellular Vesicles to Boost Skin Regeneration
Regulation of the Pigmentation Process by Exosomes
Role of Extracellular Vesicles in Hair Follicle Function
Exosomes as Signaling Mediators with the Potential to Modulate Hair Cycling
Use of Extracellular Vesicles to Stimulate Hair Growth
Immune System Cells and Hair Follicles
Findings
Concluding Remarks and Future Directions
Full Text
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