An Update on Regenerative Medicine and Exosomes

Exosomes are extracellular vesicles involved in cell-to-cell communication and are associated with immune responses as well as a variety of disease states including cancer progression.

Generated by all cells, exosomes carry nucleic acids, proteins, lipids, and metabolites and are highly variable regarding their size, content, function, and source. Currently, the utility of exosomes is being investigated in aesthetic medicine and is an active area of research. Herein, we describe some of the potential applications and mechanisms of action.

AESTHETIC APPLICATIONS

Scars (Figure A)

Causes of scarring include reduced apoptosis of fibroblasts, excessing collagen deposition, enhanced expression of TGH-B1, and delayed keratinocyte function. Current therapies to improve the appearance of atrophic, hypertrophic, and keloid scars entail surgery, laser as well as cell therapy. Animal studies have shown that adipose-derived stem cell exosomes (ADSC-exos) promote collagen synthesis and deposition by activating the PI3 Kinase Akt (PI3K/Akt) signaling pathway to shorten healing time and reduce scar formation. Umbilical cord-derived mesenchymal stem cells (uMSCs) were found to interfere with the activity of the TGF-b2/SMAD2 pathway and suppress myofibroblast differentiation. Moreover, exosomes from human-induced pluripotent stem-cell derived mesenchymal stem cells (iPSC-MSCs) have the potential to promote skin re-epithelization and angiogenesis, promote collagen maturity and reduce scar widths. Therefore, MSC-exos, including ADSC-exos, have emerged as a promising therapeutic approach to enhance wound healing and prevent scars.

Figure 1. A. Scars. B. Pigmentation regulation. C. Hair growth. D. Skin rejuvenation.

Pigment Regulation (Figure B)

Skin pigmentation depends on the delicate balance of keratinocytes and melanocytes interacting with each other in the epidermis. Environmental factors can trigger excessive melanin production and their irregular accumulation in skin cells resulting in solar lentigines, ephelides and melasma. Some studies have shown that certain keratinocyte exosomes can induce as well as suppress melanocyte inducing transcription factor (MITF)-dependent signaling pathways. Exosomes are currently being explored to regulate melanogenesis and potential therapeutic applications to inhibit pigmentation.

Hair Growth (Figure C)

A burgeoning area of interest for exosomes is the hair growth. Hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) play important roles in hair growth and regeneration and are the targets of medications such as minoxidil or finasteride. DPC-exos can regulate hair follicle growth at different stages and encourage the proliferation and differentiation of outer root sheath cells (ORSCs). In animal studies, DPC-exos were found to increase IGF-1, KGF, and HGF expression, enhance proliferation and migration of ORSCs, as well as accelerate the onset of anagen and delay catagen hair cycles.

Skin Rejuvenation (Figure D)

Due to intrinsic and extrinsic factors, the skin undergoes a variety of changes with age and the number of human dermal fibroblasts (HDFs) decreases with time. These dermal fibroblasts are responsible for the synthesis of procollagen and elastic fibers. Recently, studies have shown that exosomes derived from the three-dimensional culture of HDFs spheroids (3D-HDF-exos) can increase procollagen type 1 and decrease matrix metalloproteinases 

(MMP)-1 expression through modulating the transforming growth factor (TGF)a and TGFb pathways.1An incredible amount of interest has emerged regarding the application of exosomes in skin aging that many companies have taken the lead to produce therapies for home and in-office use (See Table 1).

1. Xiong M, Zhang Q, Hu W,et al. The novel mechanisms and applications of exosomes in dermatology and cutaneous medical aesthetics. Pharmacol Res. 2021 Apr;166:105490. doi: 10.1016/j.phrs.2021.105490. Epub 2021 Feb 12. PMID: 33582246.