cosmetics

Review
Therapeutic Values of Exosomes in Cosmetics, Skin Care,
Tissue Regeneration, and Dermatological Diseases
Abhimanyu Thakur 1, *, Disheet Shah 2 , Deepika Rai 3 , Diana Carolina Parra 4 , Spoorthy Pathikonda 5 ,
Svetlana Kurilova 6 and Alma Cili 7

1 Ben May Department for Cancer Research, Pritzker School of Molecular Engineering, University of Chicago,
Chicago, IL 60637, USA
2 Department of Pharmacology, Northwestern University, Chicago, IL 60208, USA
3 Smidt Heart Institute, Cedars-Sinai Medical Centre, Los Angeles, CA 90048, USA
4 Tropical Disease Laboratory, Department of Genetics, Evolution, Microbiology and Immunology, Institute of
Biology, University of Campinas (UNICAMP), São Paulo 13083-970, Brazil
5 Department of Chemistry, City University of Hong Kong, Hong Kong SAR, China
6 Office of Technology Management, University of Illinois Chicago, Chicago, IL 60612, USA
7 Clinic of Hematology, University of Medicine, University Hospital Center “Mother Teresa”, “Rr. e DIbres” Nr.
372, 1001 Tirane, Albania
* Correspondence: abithakur1211@gmail.com

Abstract: Exosomes are small extracellular nanovesicles that are released by cells, and their potential
has been explored for use in cosmetics, skin care, tissue regeneration, and dermatological diseases.
The therapeutic value of exosomes lies in their ability to modulate the microenvironment of cells,
regulate gene expression, and induce cell differentiation, which can have a positive impact on skin
health. In terms of cosmetics, exosomes have been used to reduce wrinkles, improve skin texture and
hydration, and enhance skin elasticity, as well as to reduce inflammation and damage caused by UV
radiation. Furthermore, exosomes have been used to promote tissue regeneration in skin wounds and
to treat dermatological diseases such as systemic lupus erythematosus, psoriasis, atopic dermatitis,
systemic sclerosis, pigment regulation, vitiligo, and hair growth. In this review, the therapeutic value
of exosomes in the field of cosmetics, skin care, tissue regeneration, and dermatological diseases,
Citation: Thakur, A.; Shah, D.; Rai, has been elaborated. The existing literature demonstrated that with further research, exosomes may
D.; Parra, D.C.; Pathikonda, S.; become a viable therapeutic option for many skin conditions.
Kurilova, S.; Cili, A. Therapeutic
Values of Exosomes in Cosmetics, Keywords: exosome; skin disease; tissue regeneration; cosmetics; dermatological research
Skin Care, Tissue Regeneration, and
Dermatological Diseases. Cosmetics
2023, 10, 65. https://doi.org/10.3390/
cosmetics10020065
1. Introduction
Academic Editor: Enzo Berardesca Exosomes are nano-sized vesicles that are typically 30–200 nanometers in diameter,
Received: 20 March 2023
and they contain a variety of proteins, lipids, and genetic material such as mRNA and
Revised: 12 April 2023
miRNA [1–4]. Exosomes are released from many different types of cells, including stem
Accepted: 14 April 2023 cells, and they can circulate in the bloodstream. Exosomes originate from the inward
Published: 20 April 2023 budding of multivesicular bodies (MVBs) containing intraluminal vesicles (ILVs) and they
are released via the endosomal-lysosomal pathway. They are thought to play a role in
intercellular communication. They engage in many biological processes including cell-to-
cell communication, tissue repair, and immune system modulation. They contain a variety
Copyright: © 2023 by the authors. of molecules, including proteins and nucleic acids [5,6], and exhibit a variety of functions,
Licensee MDPI, Basel, Switzerland. including immune modulation and the delivery of messages between cells. Exosomes
This article is an open access article are also known to possess anti-inflammatory and immunomodulatory properties, which
distributed under the terms and make them attractive for use in skin flap reconstruction. The cosmetics industry has seen a
conditions of the Creative Commons
surge in demand for skin care products in recent years. This is driven by several factors
Attribution (CC BY) license (https://
including an increased focus on self-care, the rising popularity of social media, and the
creativecommons.org/licenses/by/
growing awareness of the dangers of sun exposure. The self-care trend is partly driven by
4.0/).

Cosmetics 2023, 10, 65. https://doi.org/10.3390/cosmetics10020065 https://www.mdpi.com/journal/cosmetics

 Cosmetics 2023, 10, 65 2 of 14

the idea that people should take care of their skin since it’s the largest organ in the body [7].
Consumers are increasingly looking for natural, organic, and cruelty-free products that
are formulated with ingredients that are safe and beneficial for their skin. Products like
facial moisturizers, serums, and masks are becoming more popular, as they provide a way
to nourish and protect the skin from environmental damage. Social media has also had
a major impact on the cosmetics industry [8]. From influencers showcasing their beauty
routines to popular makeup tutorials, people now have easy access to information about
skin care products and trends. This has helped to create a demand for products that can
help individuals achieve a certain look or level of beauty. Finally, the growing awareness of
the dangers of sun exposure has led to an increased demand for sun protection products.
Consumers are looking for sunscreen, moisturizers, and other products that are specifically
designed to protect their skin from the sun’s harmful rays [8,9]. Overall, the cosmetics
industry has seen a steady increase in demand for skin care products. This is driven by a
combination of factors, including self-care, social media, and the need for sun protection.
As consumers become more conscious of the importance of taking care of their skin, this
trend is likely to continue. Though we have seen and read multiple literature reviews on
the broad topic covering one area or another, in this review, we focused on all the possible
areas where exosomes have been used and cited in the last decade.

2. Exosomes in Cosmetics Industry

Exosomes have recently been gaining attention in the cosmetic world [10]. Used
in topical creams, serums, and masks, exosomes have been found to have a number of
therapeutic and anti-aging benefits [11]. Exosomes have been found to be beneficial for
skin care, as they are filled with proteins, lipids, and other molecules that can help to
promote healing, hydration, and the protection of the skin. These molecules can help to
boost collagen production, reduce inflammation, and protect the skin from environmental
stressors. Additionally, exosomes can help to increase the efficacy of other active ingredients,
such as hyaluronic acid, peptides, and antioxidants [11]. Figure 1 depicts Adipose stem cell
derived-condition media (ASC-CM), Bone marrow stem cell derived (BMSC)-exosomes,
decreased reactive oxygen species (ROS), as well as TNF-α and increased TGF-β, resulting
in higher MMP-1 and pro-collagen type I. This led to the increase of collagen synthesis, the
improvement of elasticity, and the reduction of wrinkles, an effective anti-aging therapy [12].
Filled with molecules that help stimulate collagen production, exosomes can help to reduce
wrinkles and fine lines [13]. Additionally, exosomes can help to repair skin damage such as
sun damage and acne scars. Exosomal proteins and lipids can help to plump and hydrate
the skin, which can help to improve skin texture. Ingredients of exosomes such as cytokines,
nucleic acids, proteins, and other bioactive compounds can also help to protect the skin from
x FOR PEER REVIEW environmental stressors and reduce the appearance of dark spots and other3 discoloration.
of 14
With their ability to help improve skin tone, texture, and appearance, exosomes provide
several promising therapeutic and anti-aging benefits.

Figure 1. Role of exosomes

Figure 1.for anti-aging
Role treatment.
of exosomes The treatment.
for anti-aging administration of ASC-CMofand
The administration BMSC-exos
ASC-CM and BMSC-exos
had the effect of decreasing the production
had the effect of decreasing of
thereactive oxygen
production species
of reactive (ROS)
oxygen to a(ROS)
species low to
level,
a lowdecreas-
level, decreasing
ing the expression of tumor necrosis factor-alpha (TNF-α) but increasing the expression of trans-
forming growth factor-beta (TGF-β), leading to an increase in the production of matrix metallopro-
teinase-1 (MMP-1) and pro-collagen type I, which ultimately enhanced the synthesis of collagen in
the skin, improving its elasticity and reducing the appearance of wrinkles, making it an effective
Cosmetics 2023, 10, 65 Figure 1. Role of exosomes for anti-aging treatment. The administration of ASC-CM and BMSC-exos 3 of 14
had the effect of decreasing the production of reactive oxygen species (ROS) to a low level, decreas-
ing the expression of tumor necrosis factor-alpha (TNF-α) but increasing the expression of trans-
forming growth factor-beta (TGF-β), leading to an increase in the production of matrix metallopro-
teinase-1 (MMP-1) and pro-collagen type I, which ultimately enhanced the synthesis of collagen in
the skin,
the expression of tumor
improving its necrosis
elasticityfactor-alpha (TNF-α)
and reducing but increasing
the appearance ofthe expression
wrinkles, of transforming
making it an effective
anti-aging therapy.(TGF-β),
growth factor-beta Figure was created
leading using
to an Biorender.
increase in the production of matrix metalloproteinase-1
(MMP-1) and pro-collagen type I, which ultimately enhanced the synthesis of collagen in the skin,
3.improving
Role of its
Exosomes in Wound
elasticity and reducingHealing
the appearance of wrinkles, making it an effective anti-aging
therapy. Figure was
Exosomes created
have beenusing Biorender.
studied extensively in the context of wound healing, particu-
larly in the context of burn wounds [14]. During injury, the cells release exosomes to help
3. Role of Exosomes in Wound Healing
the wound heal. These immune cells help to clean the wound and reduce the risk of infec-
Exosomes have
tion. Exosomes also been studied
contain extensively in the
pro-inflammatory contextthat
proteins of wound healing,
stimulate particularly
the release of cyto-
in the context of burn wounds [14]. During injury, the cells release
kines and chemokines. These cytokines and chemokines initiate the recruitment of im- exosomes to help
the wound heal. These immune cells help to clean the wound and reduce the risk of
mune cells to the wound site and activate wound healing. In addition, exosomes contain
infection. Exosomes also contain pro-inflammatory proteins that stimulate the release of
growth factors that stimulate the growth of fibroblasts, which helps to close the wound
cytokines and chemokines. These cytokines and chemokines initiate the recruitment of
[15]. Exosomes also promote cell-to-cell communication. They contain miRNAs that are
immune cells to the wound site and activate wound healing. In addition, exosomes contain
proven
growth to regulate
factors gene expression
that stimulate in the
the growth cells around
of fibroblasts, the helps
which wound [16]. This
to close promotes
the wound [15]. the
formation
Exosomes alsoof new blood
promote vessels, communication.
cell-to-cell increasing the blood flow tomiRNAs
They contain the wound site.
that are This in-
proven
creased blood flow then delivers oxygen and nutrients to the wound, which
to regulate gene expression in the cells around the wound [16]. This promotes the formation further speeds
up the healing process [17]. Adipose-derived stem cells (ASCs) and their
of new blood vessels, increasing the blood flow to the wound site. This increased blood exosomes have
been shown
flow then to have
delivers a therapeutic
oxygen and nutrients role in wound,
to the treatingwhich
aberrant skin
further conditions,
speeds including
up the healing
wound
processhealing, acne, and alopecia.
[17]. Adipose-derived ASC-exosomes
stem cells (ASCs) and havetheir been shown
exosomes to reduce
have inflamma-
been shown to
haveand
tion a therapeutic roleproduction
increase the in treating aberrant skin conditions,
of extracellular matrixincluding
and growth wound healing,
factors, acne, in
resulting
and alopecia.
improved skinASC-exosomes have been
quality and healing shown
(Figure 2). to reduce exosomes
Overall, inflammation playand
an increase
important therole
production of
in wound healing. extracellular matrix and growth factors, resulting in improved skin quality
and healing (Figure 2). Overall, exosomes play an important role in wound healing.

Figure 2. Therapeutic role of adipose-derived stem cells (ASC-exosomes) in aberrant skin conditions.
Exosomes released from ASC-exosomes have been found to have regenerative and anti-inflammatory
effects on the skin, helping to improve its appearance and texture. These exosomes are thought
to reduce wrinkles and pigmentation, as well as promote collagen production. Figure was created
using Biorender.

4. Role of Exosomes in the Reconstruction of Skin Flaps

The potential use of exosomes in skin flap reconstruction has been studied in recent
years, with promising results in studies conducted on rats [17]. The use of exosomes in skin
flap reconstruction involves the injection of exosomes directly into the skin flap in order to
promote angiogenesis and wound healing. Studies have shown that the injection of adipose
Cosmetics 2023, 10, 65 4 of 14

mesenchymal stem cell (MSC)-derived exosomes into a skin flap can significantly improve
the survival rate of the flap, as well as reduce the amount of scarring that occurs [18,19]. In
addition to their potential use in skin flap reconstruction, exosomes have also been studied
for their potential to promote skin regeneration. Studies have shown that the injection of
exosomes into the skin can stimulate the production of collagen and elastin, two substances
that are essential for skin regeneration [20]. This is important for skin flap reconstruction,
as these substances are necessary for the formation of the new skin that will form during
the reconstruction process. Overall, the unique properties of exosomes, including their anti-
inflammatory and immunomodulatory properties, their ability to promote angiogenesis
and wound healing, and their potential to promote skin regeneration, make them an
attractive option for reconstructive surgery. Further research is needed to fully understand
their role in skin flap reconstruction and to determine the most effective ways to use them.

5. Role of Exosomes in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multi-
ple organs, including the skin, muscles, and joints. The cause of SLE is unknown, but
it is believed to be the result of an environmental trigger, combined with genetic and
immunological factors [21]. In recent years, researchers have begun to focus on the role
of exosomes in SLE. In SLE, exosomes have been found to play an important role in the
development and progression of the disease. Exosomes from SLE patients have been found
to contain higher levels of cytokines, chemokines, and other molecules that can promote
inflammation [22]. These molecules can also activate other cells of the immune system,
leading to increased production of antibodies that can attack the body’s tissues. Exosomes
can also be used as biomarkers to diagnose and monitor SLE [23]. Serum exosomes have
been found to contain a variety of molecules that can be used to distinguish SLE from other
autoimmune disorders [24–26]. SLE patients-derived exosomes have also been found to
contain higher levels of certain molecules, such as interferon-gamma and interleukin-17,
which can be used to monitor the progress of the disease. In addition, exosomes can be
used to deliver therapeutic molecules to SLE patients. For example, exosomes loaded
with anti-inflammatory molecules can be used to reduce inflammation in SLE patients.
Similarly, exosomes loaded with immunosuppressive molecules can be used to reduce
the production of antibodies that can attack the body’s tissues. Evidently, exosomes can
be used to diagnose and monitor SLE, as well as to deliver therapeutic molecules to SLE
patients. As researchers continue to explore the role of exosomes in SLE, they may be able
to develop new treatments that can improve the lives of SLE patients [24–26].

6. Role of Exosomes in Psoriasis

Psoriasis is a chronic inflammatory skin disease that affects over 125 million people
worldwide [27]. It is characterized by patches of red, scaly skin and is caused by an
overactive immune system. While there is no cure for psoriasis, recent research has shown
that exosomes may play a role in its treatment. In the case of psoriasis, exosomes are
believed to play a role in the overactive immune response that leads to psoriasis. The
exact mechanism by which exosomes contribute to psoriasis is still not fully understood.
However, some studies have suggested that exosomes could be used to modulate the
immune system to reduce inflammation and improve skin health. For example, exosomes
derived from a certain type of immune cell (regulatory T cells) have been shown to suppress
inflammation in mice with psoriasis-like skin conditions. Exosomes could also be used to
deliver therapeutic agents directly to the affected areas. For example, exosomes loaded
with anti-inflammatory drugs have been shown to reduce psoriasis-like skin lesions in
mice [28]. In addition, exosomes loaded with small interfering RNAs (siRNAs) have been
shown to reduce skin inflammation in a mouse model of psoriasis [29]. Overall, exosomes
appear to be promising candidates for the treatment of psoriasis. While further research is
needed to identify their role in psoriasis, exosomes could provide a novel way to target
and modulate the immune system to reduce inflammation and improve skin health.
 7. Role of Exosomes in Atopic Dermatitis
Atopic dermatitis (AD), also known as eczema, is a chronic skin inflammation caused
by an underlying immune system disorder. It is characterized by red, itchy, and scaly
Cosmeticsrashes [27,30]. The exact cause of AD is not known, but it is believed to be caused by a5 of 14
2023, 10, 65
combination of genetic and environmental factors [31]. Exosomes released from T cells,
mast cells, and keratinocytes have been found to contain inflammatory mediators that can
induce or aggravate 7. Role of Exosomes
AD [32]. in Atopicexosomes
For example, Dermatitis released from T cells can activate
Atopic dermatitis
mast cells in the skin, leading (AD), also
to the release known as eczema,
of inflammatory is a chronicsuch
mediators skin inflammation
as histamine, caused
by an underlying immune system disorder. It is characterized by red, itchy, and scaly
which can induce itching and inflammation. Exosomes released from keratinocytes can
rashes [27,30]. The exact cause of AD is not known, but it is believed to be caused by a
also contain inflammatory
combination mediators
of geneticsuch as IL-4 and IL-13,
and environmental which
factors [31]. can promote
Exosomes released the
fromre- T cells,
cruitment of inflammatory
mast cells,cells and exacerbate
and keratinocytes atopic
have been dermatitis.
found to containExosomes
inflammatory can also play
mediators that can
a role in modulating the immune
induce or aggravate system in atopic
AD [32]. dermatitis.
For example, exosomes Forreleased
instance,fromexosomes
T cells can re-
activate
mast cells in the skin, leading to the release of inflammatory
leased from keratinocytes have been found to contain anti-inflammatory mediators such mediators such as histamine,
which can induce itching and inflammation. Exosomes released from keratinocytes can
as transforming growth factor beta (TGF-β), which can suppress the activation of T cells
also contain inflammatory mediators such as IL-4 and IL-13, which can promote the re-
and reduce inflammation.
cruitmentExosomes
of inflammatoryreleased from
cells and mast cells
exacerbate can
atopic also contain
dermatitis. Exosomesregulatory
can also play
cytokines such as IL-10a roleand TGF-β, which
in modulating can suppress
the immune system the activation
in atopic of T cells
dermatitis. and reduce
For instance, exosomes
inflammation. In addition, exosomes have been found to contain immunomodulatory such
released from keratinocytes have been found to contain anti-inflammatory mediators
molecules such as as transforming growth factor beta (TGF-β), which can suppress the activation of T cells
microRNAs, that are shown to regulate the expression of genes in-
and reduce inflammation. Exosomes released from mast cells can also contain regulatory
volved in immune cytokines
responses. For example,
such as IL-10 exosomes
and TGF-β, which canreleased
suppressfrom mast cells
the activation of Thave been
cells and reduce
found to contain microRNAs
inflammation. that
In stimulate the downregulation
addition, exosomes have been found oftopro-inflammatory
contain immunomodulatory cy-
tokines expressionsmolecules
such assuch IL-4asand IL-13 which
microRNAs, that arehave
shown been shown
to regulate theto reduce inflamma-
expression of genes involved
in immune responses. For example, exosomes
tion. Overall, exosomes play a key role in the development and progression of atopicreleased from mast cells have been
der-found
to contain microRNAs that stimulate the downregulation of pro-inflammatory cytokines
matitis. Shin et al. expressions
showed that ASC-exosomes have been found to reduce symptoms of
such as IL-4 and IL-13 which have been shown to reduce inflammation. Overall,
AD. Studies have demonstrated
exosomes play a that these
key role exosomes
in the development canandreduce inflammation
progression and pro- Shin
of atopic dermatitis.
mote skin barrier restoration by increasing ceramide and dihydroceramide production.
et al. showed that ASC-exosomes have been found to reduce symptoms of AD. Studies
have demonstrated
This suggests ASC-exosomes could that
be athese
viableexosomes
treatmentcan reduce
option inflammation
for AD, asand promote
there are lim-skin bar-
rier restoration by increasing ceramide and dihydroceramide production. This suggests
ited available treatments. Therefore, this cell-free therapy could provide much-needed re-
ASC-exosomes could be a viable treatment option for AD, as there are limited available
lief for those suffering from this
treatments. condition
Therefore, (Figure
this cell-free 3) [33].
therapy Further
could provideresearch
much-needed is needed
relief fortothose
better understand the role of
suffering from exosomes in AD
this condition and3)to
(Figure develop
[33]. Further potential therapeutic
research is needed to betterstrate-
understand
the role of
gies to target these exosomes [33,34].exosomes in AD and to develop potential therapeutic strategies to target these
exosomes [33,34].

Figure 3. Role of exosomes in ameliorating atopic dermatitis (AD). ASC-exosomes improved hy-
dration, lowered cytokines IL-4, IL-5, IL-13, IFN-γ, and TNF-α, reduced mast cells and DECs in
lesions, and made ceramides to repair the epidermis, thereby alleviating AD. Figure was created
using Biorender.

8. Role of Exosomes in Systemic Sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by progressive
fibrosis of the skin and internal organs. Patients with SSc suffer from a variety of symptoms,
including Raynaud’s phenomenon, skin thickening, and organ fibrosis [34,35]. While the
etiology of SSc is still unknown, recent evidence has suggested that exosomes may play
an important role in the progression of this disease. Exosomes are small vesicles released
by cells that contain a variety of molecules, including proteins, lipids, and RNA. In SSc,
Cosmetics 2023, 10, 65 6 of 14

exosomes are thought to contribute to the development of fibrosis by releasing pro-fibrotic

molecules, such as transforming growth factor-beta (TGF-β). In addition, exosomes from
SSc patients have been found to contain increased levels of pro-inflammatory cytokines,
such as interleukin-6 (IL-6), which can promote the development of sclerosis [36]. Exosomes
from SSc patients have also been found to contain specific microRNAs (miRNAs) that are
associated with the development of fibrosis. These miRNAs are thought to be involved
in the regulation of gene expression and can thus contribute to the progression of fibrosis.
In addition, exosomes from SSc patients have been found to contain increased levels of
matrix metalloproteinases (MMPs), which are enzymes involved in the breakdown of an
extracellular matrix [25]. The increased levels of these enzymes are thought to contribute to
the development of skin and organ fibrosis. In summary, exosomes have been implicated
in the progression of SSc. They are thought to be involved in the release of pro-fibrotic
molecules as well as increased levels of pro-inflammatory cytokines and MMPs. In addition,
they contain specific miRNAs that can regulate gene expression and thus contribute to the
progression of the disease [34]. Further research is needed to better understand the role of
exosomes in SSc and to develop potential therapies targeting these exosomes.

9. Role of Exosomes in Scar Removal

In recent years, researchers have been exploring the potential of exosome therapy for
scar removal. Exosome-based scar removal works by delivering therapeutic agents directly
to the affected area. Exosomes can deliver cytokines and growth factors that stimulate
the production of new collagen and elastin, which is shown to simulate the reduction of
scars [11]. Exosome therapy can be applied topically or injected directly into the scar tissue.
Injections are often used to treat deeper scars, as they can effectively penetrate the dermis
where the scar tissue is located. Topical applications may be more suitable for superficial
scars, as they can provide a more even distribution of the therapeutic agents. In clinical
studies, exosome therapy has been found to be safe and effective for scar removal [37].
It can reduce the appearance of scars, improve skin hydration and elasticity, and reduce
inflammation. It can also help to strengthen the skin’s natural defenses against infection.
Exosomes derived from umbilical cord-derived MSCs (uMSCs) are enriched in specific
miR-21, miR-23a, miR-125b, and miR-145 [38]. A skin-defect mouse model showed that
these exosomes could suppress fibrosis and scar formation by interfering with the TGF-
β2/SMAD2 pathway. Additionally, exosomes high in miR-21-3p were shown to accelerate
re-epithelialization, reduce scar widths, and promote angiogenesis via inhibition of PTEN
and SPRY1 [39]. These findings suggest that MSC-derived exosomes, including ADSC-exos,
may regulate fibroblast function and collagen deposition to promote scarless healing. Thus,
ADSC-exos represent a potential therapeutic approach for improving wound healing and
scar prevention (Figure 4). Evidently, exosome therapy is a promising treatment for scar
removal, but further research is needed to understand its full potential. If proven effective,
it could provide an alternative to more invasive treatments, such as laser resurfacing and
chemical peels. As the technology continues to evolve, it may become a viable option for
those looking to reduce the appearance of their scars [39].
OR PEER REVIEW 7 of 14

laser resurfacing and chemical peels. As the technology continues to evolve, it may be- 7 of 14
Cosmetics 2023, 10, 65
come a viable option for those looking to reduce the appearance of their scars [39].

Figure 4. Role of exosomes inRole

Figure 4. the of
treatment
exosomes of scars.
in the MSC-derived
treatment exosomes exosomes
of scars. MSC-derived from umbilical cords cords
from umbilical
showed enrichment inshowed
specific miRNAs,
enrichment including
in specific miR-21,
miRNAs, -23a,miR-21,
including -125b, -23a,
and -125b,
-145. and
Their application
-145. Their application
to a mouse skin-defecttomodel
a mouse skin-defect
reduced modelresulting
fibrosis, reduced fibrosis,
in less resulting
scarring.inAdditionally,
less scarring. Additionally,
human um-human
bilical cord-derived exosomes containing miR-21–3p accelerated re-epithelialization, reducedreduced
umbilical cord-derived exosomes containing miR-21–3p accelerated re-epithelialization, scar scar
widths, and boosted
widths, and boosted angiogenesis. angiogenesis.
Thus, MSC-derived Thus, MSC-derived
exosomes couldexosomes could regulate
regulate fibroblasts,
fibroblasts, collagen
colla-
deposition, and promote scarless wound healing. Figure was created using Biorender.
gen deposition, and promote scarless wound healing. Figure was created using Biorender.
10. Role of Exosomes in the Rejuvenation of the Face
10. Role of Exosomes inThe thefield
Rejuvenation of the Face
of facial rejuvenation has seen a wide variety of treatments, from laser
resurfacing
The field of facial to chemical
rejuvenation has peels.
seen aInwide
the midst of this,
variety of atreatments,
new technique fromis gaining
laser re-traction:
surfacing to chemical peels. In the midst of this, a new technique is gaining traction: exo-body’s
exosome facial rejuvenation. This innovative procedure uses stem cells and the
natural healing powers to produce long-lasting, natural-looking results. Exosomes are
some facial rejuvenation.
thought This innovative
to help with tissueprocedure uses
regeneration and stem
cell cells and theand
rejuvenation bodyare s natural
being used as a
healing powers to produce long-lasting,
way to promote natural-looking
facial rejuvenation [40]. Theresults. Exosomes
process begins with aare thought
biopsy to the
of fat from
help with tissue regeneration and cell rejuvenation and are being used as a way to pro- cells
patient, which is then processed to extract the stem cells and exosomes. The stem
and their
mote facial rejuvenation exosomes
[40]. are then begins
The process injected into
withthea facial
biopsy skin,ofwhich is shown
fat from thetopatient,
stimulate the
body’s natural healing process. The exosome facial rejuvenation process can help to reduce
which is then processed to extract the stem cells and exosomes. The stem cells and their
wrinkles, dark circles, and age spots. The process also helps to improve skin tone and
exosomes are then texture,
injectedasinto
well the facial collagen
as increase skin, which is shown
production. to stimulate
Exosome injections the
havebody s of
been part
natural healing process. The
clinical exosome
studies but havefacial rejuvenation
yet to be granted FDA process
approval can forhelp
use astoinjections
reduce wrin-
[41].
kles, dark circles, and age spots. The process also helps to improve skin tone and texture,
11. Role of Exosomes in the Regulation of Pigmentation
as well as increase collagen production. Exosome injections have been part of clinical stud-
Recent studies have identified that exosomes may play an important role in the regu-
ies but have yet to be granted
lation FDA approval
of pigmentation fororganisms,
in multiple use as injections
including[41].
humans, through several different
mechanisms. Exosomes have been shown to regulate the expression of genes involved in
11. Role of Exosomes in the Regulation
pigmentation and provideof
an Pigmentation
efficient way for cells to transfer melanin-producing enzymes
to other cells, enabling them to synthesize and produce melanin [42]. Studies have shown
Recent studies have identified that exosomes may play an important role in the reg-
that exosomes can stimulate the activity of tyrosinase, leading to an increase in melanin
ulation of pigmentation in multiple
production organisms,
[43]. Additionally, including
exosomes humans,
can regulate through several
the expression differ-
of tyrosinase, which is
ent mechanisms. Exosomes have been shown to regulate the expression of genes involved
important for modulating the production of melanin. Keratinocytes-derived exosomes have
in pigmentation andbeen shown an
provide to activate
efficient melanocyte
way forprecursors and induce
cells to transfer their differentiation into
melanin-producing en-mature
melanocytes. Furthermore, exosomes can help to stimulate the migration of melanocytes
zymes to other cells, enabling them to synthesize and produce melanin [42]. Studies have
to areas of the skin where pigment production is needed. In conclusion, exosomes can
shown that exosomes helpcan stimulate
to regulate the the activity
expression of tyrosinase,
of genes involved inleading to an provide
pigmentation, increasea way
in for
melanin productioncells
[43]. Additionally,
to transfer exosomesenzymes,
melanin-producing can regulate the expression
and regulate of expression
the activity and tyrosi- of
nase, which is important for modulating the production of melanin. Keratinocytes-de-
tyrosinase. Additionally, exosomes can help to regulate the development and migration of
rived exosomes have melanocytes.
been shown Therefore, a better
to activate understanding
melanocyte of the roleand
precursors of exosomes
induce in pigmentation
their dif-
could be beneficial for the development of therapeutic agents to treat skin disorders.
ferentiation into mature melanocytes. Furthermore, exosomes can help to stimulate the
migration of melanocytes to areas of the skin where pigment production is needed. In
conclusion, exosomes can help to regulate the expression of genes involved in pigmenta-
tion, provide a way for cells to transfer melanin-producing enzymes, and regulate the ac-
tivity and expression of tyrosinase. Additionally, exosomes can help to regulate the de-
velopment and migration of melanocytes. Therefore, a better understanding of the role of
exosomes in pigmentation could be beneficial for the development of therapeutic agents
Cosmetics 2023, 10, 65 8 of 14

12. Role of Stem Cell-Derived Exosomes in Cosmetic Dermatology

Stem cell-derived exosomes are from pluripotent stem cells, mesenchymal stem cells,
and adipose stem cells [44]. The stem-cell-derived exosomes are like the other exosomes
derived from other cells, morphologically and structurally, and their difference is between
their surface proteins and the information transmitted within the membrane [44,45]. Stem
cell exosomes possess unique abilities for cell proliferation, regeneration, and wound
healing [45]. One such example is an alteration of extracellular matrix compositions and
fibroblast proliferation [45]. Thus, because of these properties, stem cell-derived exosomes
can play a vital role in skin rejuvenation, skin microenvironment, and wound repair during
acne healing [44,45]. As we know, skin aging results from both internal and external factors.
Internally it is based on gene dependence for aging and skin texture [44,45]. However,
externally, multiple factors are responsible for this, such as ultraviolet B (280–320 nm) (UV-
B) light, which induces DNA mutations and increases oxidative stress on the cells which
leads to skin aging [46]. Apart from this, UV-B can also simulate MAPK signaling pathways,
further enhancing the expression of MMPs and leading to downregulating collagen type I
by activator protein-1 [47,48]. Through other research, we know that collagen type I and
III syntheses are essential aspects of ECM, as they eventually make skin look younger
and fuller, leading to skin aging [45,49]. Apart from this, as the dermis fibroblast ages,
it will ultimately lead to reduced collagen [12] and, along with the expression of MMPs,
it will lead to cleavage of existing collagen which leads to skin aging symptoms such as
wrinkles and pigmentation [50–52]. Senescence studies on the skin have proven that stem
cell-derived exosomes are vital in reducing skin aging (Figure 5). Exosomes derived from
human induced pluripotent stem cells (iPSCs) can reduce the aging of human dermal
fibroblasts. It has been shown that iPSCs expression can regulate the expression level of
MMP-1/3 and thus, in turn, increase the expression of type 1 collagen and reduced skin
aging [50–52]. Furthermore, this will reduce the expression of senescence-associated-β-
gaalctosidase (SA-β-Gal) [45]. Apart from a reduction in senescence, stem cell-derived
exosomes play an essential role in wound healing [53,54]. As wound healing involves
inflammation, hyperplasia, and remodeling, inflammation is regulated by the polarization
of macrophages into an M2 phenotype [53]. It has been observed that exosomes secreted by
human mesenchymal stem cells (hMSCs) can decrease the number of neutrophils and, in
turn, decrease the macrophage population during the inflammatory response [54]. Another
study observed conveys that exosomes impact various pathways to wound repairs, such
as the Wnt4/β-catenin signaling pathway [55], Erk1/2 signaling pathway [56], NF-κB
signaling pathway [55], and Notch signaling pathway [57]. Similarly, stem cells derived
exosomes play a vital role in scarless healing [57]. The presence of fine reticular collagen,
lesser inflammation at the recovery site, fewer myofibroblasts, and fewer cross-linking
define scarless healing [58]. Apart from the presence of higher type 1 collagen, TGF β1,
and matrix metalloproteinase tissue inhibitors compared to type III collagen, TGF β3 and
MMPs expression is required for scarless healing [58,59]. Studies have shown that exosomes
derived from human adipose mesenchymal stem cells can regulate the latter expression
and thus help in scarless recovery [59].
x FOR PEER REVIEW 9 of 14
Cosmetics 2023, 10, 65 9 of 14

Figure 5. Stem cell derived exosomes enhance the proliferation and migration of skin fibroblast.
Figure 5. Stem cell derived exosomes enhance the proliferation and migration of skin fibroblast.
Exosomes from stem cells are shown to enhance proliferation and increase migration ability by
Exosomes from stem cells are shown to enhance proliferation and increase migration ability by in-
increasing MAPK and AKT etc. in the case of normal fibroblast cells. However, in the case of
creasing MAPK and AKT etc.fibroblast
senescence in the case of normal
(induced fibroblast
due to exposure cells.the
to UVB), However, in thearecase
same exosomes oftosenes-
found decrease
cence fibroblast (induced
senescence. Stem cell exosomes are found to have an impact on angiogenic ability, collagensenes-
due to exposure to UVB), the same exosomes are found to decrease synthesis,
cence. Stem cell exosomes are found
and regulation to have aninimpact
of inflammation on angiogenic
skin disorders. The greenability,
up-arrowcollagen synthesis,
depicts increased and
expression,
regulation of inflammation incolored
and the red skin disorders.
down-arrow The green
depicts up-arrow
decreased depicts increased expression, and
expression.
the red colored down-arrow depicts decreased expression.
13. Role of Exosomes in Vitiligo
13. Role of ExosomesVitiligo is a skin condition that causes the loss of skin pigment, resulting in white
in Vitiligo
patches on the skin. It affects both men and women of all ages and is more common in
Vitiligo is a people
skin condition
with dark skin that[60].
causes
Whilethe
the loss
causeofof skin pigment,
vitiligo resulting
is still unknown, thereiniswhite
evidence
patches on the skin.that It affectsit both
suggests men and women
is an autoimmune disorderof[60].
all Exosomes
ages andare is thought
more common in
to be involved
in the development of vitiligo by regulating the activity
people with dark skin [60]. While the cause of vitiligo is still unknown, there is evidence of genes involved in melanin
production [43]. Exosomes also contain antioxidants, which may help to protect against
that suggests it is an autoimmune disorder [60]. Exosomes are thought to be involved in
oxidative damage to the skin. While it is not clear how these molecules may play a role
the development inofvitiligo,
vitiligo by studies
some regulating the activity
have suggested thatof genes
they may involved in melanin
help to protect the skin frompro-UV
duction [43]. Exosomes
radiation,also contain
which antioxidants,
is thought which
to be a factor in themay help to protect
development against
of vitiligo. oxi- to
In addition
their role in the regulation of the immune system and in
dative damage to the skin. While it is not clear how these molecules may play a role in protecting the skin from oxidative
damage,
vitiligo, some studies have exosomes
suggested may that
also be involved
they in thetorepair
may help protectof damaged
the skin skinfrom cells
UV[61].
ra- By
delivering the necessary molecules to damaged cells, exosomes may help to stimulate the
diation, which is reparative
thought to be a factor
process in thethe
and promote development
formation of new of vitiligo.
skin cells.In addition tostem
Mesenchymal their
cells
role in the regulation of the immune system and in protecting the skin
(MSCs) are capable of immunomodulatory and regenerative properties, which make them from oxidative
damage, exosomes may also
a potential be involved
treatment option forin vitiligo.
the repair of damaged
By secreting skin cells [61].
immunosuppressive By de-and
cytokines
growth factors, MSCs can modulate the immune response
livering the necessary molecules to damaged cells, exosomes may help to stimulate the and increase the re-pigmentation
of vitiligo lesions. Clinical and pre-clinical studies have already demonstrated promising
reparative process and promote the formation of new skin cells. Mesenchymal stem cells
results of MSC-based therapies for vitiligo treatment (Figure 6). Overall, exosomes appear
(MSCs) are capable of immunomodulatory
to play a role in the developmentand andregenerative properties,
progression of vitiligo. Whilewhich make isthem
more research needed
a potential treatment option for
to understand theirvitiligo.
exact role,Bythey
secreting
may be aimmunosuppressive
potential target for therapies cytokines
that couldandhelp
growth factors, MSCsto improve this condition
can modulate the[61].
immune response and increase the re-pigmenta-
tion of vitiligo lesions. Clinical and pre-clinical studies have already demonstrated prom-
ising results of MSC-based therapies for vitiligo treatment (Figure 6). Overall, exosomes
appear to play a role in the development and progression of vitiligo. While more research
is needed to understand their exact role, they may be a potential target for therapies that
could help to improve this condition [61].
Cosmetics 2023,
Cosmetics 10,10,
2023, x FOR
65 PEER REVIEW 10 of 14 10 of 14

Figure
Figure 6.6.Immunomodulation
Immunomodulation by mesenchymal
by mesenchymal stem
stem cells cellsin (MSCs)
(MSCs) in vitiligo.
vitiligo. MSCs MSCs
have been shownhave been
shown to have immunomodulatory effects in vitiligo. The mechanisms
to have immunomodulatory effects in vitiligo. The mechanisms of MSC-mediated immunomod- of MSC-mediated immuno-
modulation
ulation are complex and involve both cell-cell contact-dependent mechanisms and the secretionsecretion
are complex and involve both cell-cell contact-dependent mechanisms and the
of
of various solublemediators.
various soluble mediators.These
These mediators
mediators cancan affect
affect the the activity
activity of regulatory
of regulatory T cellsT(Tregs),
cells (Tregs), T
helper 1 (Th1) cells, T helper 2 (Th2) cells, T helper 17 (Th17) cells, dendritic cells
T helper 1 (Th1) cells, T helper 2 (Th2) cells, T helper 17 (Th17) cells, dendritic cells (DCs), and (DCs), and natural
killer
natural(NK)
killercells.
(NK)Thecells.mediators include
The mediators interleukins
include interleukins(ILs), interferon-gamma
(ILs), (IFN-γ),tumor
interferon-gamma (IFN-γ), tumor necro-
sis
necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β). Figure was created using
factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β). Figure was created
Biorender.
using Biorender.

14.
14. Role ofExosomes
Role of Exosomesinin Hair
Hair Growth
Growth
Hair
Hairgrowth
growthis isa complex
a complexbiological process
biological regulated
process by numerous
regulated mechanisms,
by numerous in-
mechanisms,
cluding genetics,
including hormones,
genetics, and other
hormones, external
and other factors [62].
external Recent
factors [62].studies
Recent have discovered
studies have discov-
that exosomes, small vesicles released by cells, may play an important role in this pro-
ered that exosomes, small vesicles released by cells, may play an important role in this
cess [63]. Li et al. showed that ADSC-exosomes had a positive effect on DPC proliferation,
process [63]. Li et al. showed that ADSC-exosomes had a positive effect on DPC prolifer-
migration, and hair growth. It decreased apoptosis and increased HFs and dermis thickness.
ation, migration,
RNA-seq showed that andmiR-22
hair growth.
and TNF-αIt decreased apoptosis
were inhibited. qRT-PCRand and
increased
westernHFs and dermis
blotting
thickness.
showed theRNA-seq showed
Wnt/β-catenin that miR-22
pathway and TNF-α
was activated were
in the skin of inhibited. qRT-PCR and west-
ADSC-exosomes-treated
ern blotting
mice. Overall,showed the Wnt/β-catenin
ADSC-exosomes had positivepathway
effects was
on DPCsactivated
and hairin the skininofmice.
growth ADSC-exo-
somes-treated
This suggests that mice. Overall, ADSC-exosomes
ADSC-exosome therapy improved had positive by
hair regrowth effects on DPCs
controlling miR-22,and hair
Wnt/β-catenin,
growth in mice. and TNF-α
This pathways,
suggests thatsuggesting
ADSC-exosome it could be an effective
therapy cell-freehair
improved treatment
regrowth by
for alopecia miR-22,
controlling caused by the immune system
Wnt/β-catenin, [64]. Kwack
and TNF-α pathways, et al.suggesting
showed that exosomes
it could be an effec-
from 3D DP (3D DP-Exos) enhanced the proliferation of dermal papilla (DP) and outer
tive cell-free treatment for alopecia caused by the immune system [64]. Kwack et al.
root sheath (ORS) cells and increased the expression of growth factors (IGF-1, KGF, and
showed that exosomes from 3D DP (3D DP-Exos) enhanced the proliferation of dermal
HGF) in DP cells. When used to treat cultured human hair follicles, 3D DP-Exo treatment
papilla
increased hair and
(DP) shaftouter root sheath
elongation. (ORS) cells
Local injections of 3Dand increased
DP-Exos the expression
also triggered anagen fromof growth
factors
telogen (IGF-1, KGF, and
and prolonged HGF)
anagen in DP
in mice. cells. When
Moreover, whenused to treattreated
DP spheres cultured
withhuman
Exo werehair folli-
cles,
implanted with mouse epidermal cells, hair follicle neogenesis was enhanced. SimilarDP-Exos
3D DP-Exo treatment increased hair shaft elongation. Local injections of 3D
also triggered anagen from telogen and prolonged anagen in mice. Moreover, when DP
spheres treated with Exo were implanted with mouse epidermal cells, hair follicle neo-
genesis was enhanced. Similar outcomes were observed when Exos derived from 2D-cul-
tured DP cells (2D DP-Exo) were used. Their findings suggest that Exos derived from DP
Cosmetics 2023, 10, 65 11 of 14

outcomes were observed when Exos derived from 2D-cultured DP cells (2D DP-Exo) were
used. Their findings suggest that Exos derived from DP cells can promote hair growth
and regeneration by regulating the activity of follicular dermal and epidermal cells. These
results have implications for the development of therapeutic strategies for hair loss [65].
Wu et al. also showed that exosomes from adipose-derived stem cells could promote hair
regeneration [66]. As such, exosomes may play an important role in hair growth and hair
follicle regeneration. Further research is needed to better understand the role of exosomes
in this process.

15. Conclusions and Outlook

The cosmetics industry is constantly evolving as it is driven by consumer demand for
new and innovative products. Exosomes have been identified as potential new ingredients
in cosmetics, with the potential to provide significant cosmetic benefits. Exosomes have
been found to have a therapeutic role in wound healing, skin flap reconstruction, systemic
lupus erythematosus, psoriasis, atopic dermatitis, systemic sclerosis, scar removal, facial
rejuvenation, pigmentation regulation, vitiligo, and hair growth. Exosomes have tremen-
dous potential to revolutionize the cosmetics industry and provide more effective skin
care products. The unique properties of exosomes, such as their ability to penetrate the
skin, their high concentration of bioactive molecules, and their ability to interact with and
modulate the skin’s cells, make them desirable ingredients for cosmetic products.
The future of exosomes in the cosmetics industry appears to be very promising. As
research continues to uncover the potential of exosomes, more and more products will be
developed to take advantage of their unique properties. In addition, the use of exosomes in
combination with traditional cosmetic ingredients is likely to lead to more effective skin
care products. Finally, as technology advances, exosomes may be modified to provide
even more specific benefits, such as targeted delivery of active ingredients. In conclusion,
exosomes have the potential to revolutionize the cosmetics industry. With the help of
exosomes, the cosmetics industry is sure to continue to develop innovative and effective
skin care products in the future.
Despite the tremendous benefits of exosomes, their regulatory aspects have been a
topic of debate. The US Food and Drug Administration (FDA) has yet to officially classify
exosomes for cosmetics; therefore, it is not yet known what type of regulation should
be imposed. In the EU, exosomes for cosmetic use may be subject to regulation by the
European Commission, which could include restrictions on manufacturing, labeling, and
advertising. As exosomes are a relatively new technology, further research and discussion
are needed to understand the regulatory implications of their use.

Author Contributions: Conceptualization, A.T.; validation, A.T., D.S. and D.R.; formal analysis, A.T.;
investigation, A.T., D.S. and D.R.; resources, D.S., D.R., D.C.P., S.P., S.K. and A.C.; data curation, D.R.,
D.C.P., S.P. and S.K.; writing—original draft preparation, A.T.; writing—review and editing, D.S., D.R.
and S.K.; visualization, A.T., D.R., D.C.P. and S.P.; supervision, A.T.; project administration, A.T. All
authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Zhang, J.; Li, S.; Li, L.; Li, M.; Guo, C.; Yao, J.; Mi, S. Exosome and exosomal microRNA: Trafficking, sorting, and function.
Genom. Proteom. Bioinform. 2015, 13, 17–24. [CrossRef] [PubMed]
2. Qiu, G.; Thakur, A.; Xu, C.; Ng, S.-P.; Lee, Y.; Wu, C.-M.L. Detection of Glioma-Derived Exosomes with the Biotinylated
Antibody-Functionalized Titanium Nitride Plasmonic Biosensor. Adv. Funct. Mater. 2019, 29, 1806761. [CrossRef]
Cosmetics 2023, 10, 65 12 of 14

3. Thakur, A.; Qiu, G.; Xu, C.; Han, X.; Yang, T.; Ng, S.P.; Chan, K.W.Y.; Wu, C.M.L.; Lee, Y. Label-free sensing of exosomal MCT1
and CD147 for tracking metabolic reprogramming and malignant progression in glioma. Sci. Adv. 2020, 6, eaaz6119. [CrossRef]
[PubMed]
4. Thakur, A.; Mishra, A.P.; Panda, B.; Sweta, K.; Majhi, B. Detection of Disease-Specific Parent Cells via Distinct Population of
Nano-Vesicles by Machine Learning. Curr. Pharm. Des. 2020, 26, 3985–3996. [CrossRef]
5. Zhang, W.; Yan, Y.; Peng, J.; Thakur, A.; Bai, N.; Yang, K.; Xu, Z. Decoding Roles of Exosomal lncRNAs in Tumor-Immune
Regulation and Therapeutic Potential. Cancers 2022, 15, 286. [CrossRef]
6. Thakur, A.; Liang, L.; Ghosh, D.; Cili, A.; Zhang, K. Identification and functional analysis of exosomal miR-16-5p, miR-6721-5p,
and miR-486-5p associated with immune infiltration for potential vitiligo theranostics. Clin. Immunol. Commun. 2022, 2, 110–117.
[CrossRef]
7. Pop, R.-A.; Săplăcan, Z.; Alt, M.-A. Social Media Goes Green—The Impact of Social Media on Green Cosmetics Purchase
Motivation and Intention. Information 2020, 11, 447. [CrossRef]
8. Limbu, Y.B.; Pham, L.; Nguyen, T.T.T. Predictors of Green Cosmetics Purchase Intentions among Young Female Consumers in
Vietnam. Sustainability 2022, 14, 12599. [CrossRef]
9. Britton, A.M. The Beauty Industry’s Influence on Women in Society. Bachelor’s Thesis, University of New Hampshire, Durham,
NH, USA, 2012.
10. Zhang, Y.; Liu, Y.; Liu, H.; Tang, W.H. Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci. 2019, 9, 19.
[CrossRef]
11. Shi, H.; Wang, M.; Sun, Y.; Yang, D.; Xu, W.; Qian, H. Exosomes: Emerging Cell-Free Based Therapeutics in Dermatologic Diseases.
Front. Cell Dev. Biol. 2021, 9, 736022. [CrossRef]
12. Hu, S.; Li, Z.; Cores, J.; Huang, K.; Su, T.; Dinh, P.-U.; Cheng, K. Needle-Free Injection of Exosomes Derived from Human Dermal
Fibroblast Spheroids Ameliorates Skin Photoaging. ACS Nano 2019, 13, 11273–11282. [CrossRef] [PubMed]
13. Xiong, M.; Zhang, Q.; Hu, W.; Zhao, C.; Lv, W.; Yi, Y.; Wang, Y.; Tang, H.; Wu, M.; Wu, Y. The novel mechanisms and applications
of exosomes in dermatology and cutaneous medical aesthetics. Pharmacol. Res. 2021, 166, 105490. [CrossRef]
14. Bo, Y.; Yang, L.; Liu, B.; Tian, G.; Li, C.; Zhang, L.; Yan, Y. Exosomes from human induced pluripotent stem cells-derived
keratinocytes accelerate burn wound healing through miR-762 mediated promotion of keratinocytes and endothelial cells
migration. J. Nanobiotechnol. 2022, 20, 291. [CrossRef]
15. Xia, W.; Li, M.; Jiang, X.; Huang, X.; Gu, S.; Ye, J.; Zhu, L.; Hou, M.; Zan, T. Young fibroblast-derived exosomal microRNA-125b
transfers beneficial effects on aged cutaneous wound healing. J. Nanobiotechnol. 2022, 20, 144. [CrossRef]
16. Dai, W.; Dong, Y.; Han, T.; Wang, J.; Gao, B.; Guo, H.; Xu, F.; Li, J.; Ma, Y. Microenvironmental cue-regulated exosomes as
therapeutic strategies for improving chronic wound healing. NPG Asia Mater. 2022, 14, 75. [CrossRef]
17. Guo, L.; Chen, Y.; Feng, X.; Sun, D.; Sun, J.; Mou, S.; Zhao, K.; An, R. Oxidative stress-induced endothelial cells-derived exosomes
accelerate skin flap survival through Lnc NEAT1-mediated promotion of endothelial progenitor cell function. Stem Cell Res. Ther.
2022, 13, 325. [CrossRef] [PubMed]
18. Li, C.; Wei, S.; Xu, Q.; Sun, Y.; Ning, X.; Wang, Z. Application of ADSCs and their Exosomes in Scar Prevention. Stem Cell Rev. Rep.
2022, 18, 952–967. [CrossRef]
19. Hong, P.; Yang, H.; Wu, Y.; Li, K.; Tang, Z. The functions and clinical application potential of exosomes derived from adipose
mesenchymal stem cells: A comprehensive review. Stem Cell Res. Ther. 2019, 10, 242. [CrossRef]
20. Yang, G.H.; Lee, Y.B.; Kang, D.; Choi, E.; Nam, Y.; Lee, K.H.; You, H.-J.; Kang, H.J.; An, S.H.; Jeon, H. Overcome the barriers of the
skin: Exosome therapy. Biomater. Res. 2021, 25, 22. [CrossRef]
21. Cojocaru, M.; Cojocaru, I.M.; Silosi, I.; Vrabie, C.D. Manifestations of systemic lupus erythematosus. Maedica 2011, 6, 330–336.
22. Lee, J.Y.; Park, J.K.; Lee, E.Y.; Lee, E.B.; Song, Y.W. Circulating exosomes from patients with systemic lupus erythematosus induce
an proinflammatory immune response. Arthritis Res. Ther. 2016, 18, 264. [CrossRef] [PubMed]
23. Fei, Y.; Liu, Q.; Peng, N.; Yang, G.; Shen, Z.; Hong, P.; Wang, S.; Rui, K.; Cui, D. Exosomes as Crucial Players in Pathogenesis of
Systemic Lupus Erythematosus. J. Immunol. Res. 2022, 2022, 8286498. [CrossRef] [PubMed]
24. Xu, K.; Liu, Q.; Wu, K.; Liu, L.; Zhao, M.; Yang, H.; Wang, X.; Wang, W. Extracellular vesicles as potential biomarkers and
therapeutic approaches in autoimmune diseases. J. Transl. Med. 2020, 18, 432. [CrossRef] [PubMed]
25. Zhu, T.; Wang, Y.; Jin, H.; Li, L. The role of exosome in autoimmune connective tissue disease. Ann. Med. 2019, 51, 101–108.
[CrossRef]
26. Miao, C.; Wang, X.; Zhou, W.; Huang, J. The emerging roles of exosomes in autoimmune diseases, with special emphasis on
microRNAs in exosomes. Pharmacol. Res. 2021, 169, 105680. [CrossRef]
27. Bu, J.; Ding, R.; Zhou, L.; Chen, X.; Shen, E. Epidemiology of Psoriasis and Comorbid Diseases: A Narrative Review. Front. Im-
munol. 2022, 13, 880201. [CrossRef]
28. Zhang, B.; Lai, R.C.; Sim, W.K.; Choo, A.B.H.; Lane, E.B.; Lim, S.K. Topical Application of Mesenchymal Stem Cell Exosomes
Alleviates the Imiquimod Induced Psoriasis-Like Inflammation. Int. J. Mol. Sci. 2021, 22, 720. [CrossRef]
29. Nemati, H.; Ghahramani, M.H.; Faridi-Majidi, R.; Izadi, B.; Bahrami, G.; Madani, S.H.; Tavoosidana, G. Using siRNA-based
spherical nucleic acid nanoparticle conjugates for gene regulation in psoriasis. J. Control. Release 2017, 268, 259–268. [CrossRef]
30. Lu, Z.; Zeng, N.; Cheng, Y.; Chen, Y.; Li, Y.; Lu, Q.; Xia, Q.; Luo, D. Atopic dermatitis and risk of autoimmune diseases: A
systematic review and meta-analysis. Allergy Asthma Clin. Immunol. 2021, 17, 96. [CrossRef]
Cosmetics 2023, 10, 65 13 of 14

31. Wang, W.M.; Wu, C.; Jin, H.Z. Exosomes in chronic inflammatory skin diseases and skin tumors. Exp. Dermatol. 2019, 28, 213–218.
[CrossRef]
32. Shao, S.; Fang, H.; Li, Q.; Wang, G. Extracellular vesicles in Inflammatory Skin Disorders: From Pathophysiology to Treatment.
Theranostics 2020, 10, 9937–9955. [CrossRef] [PubMed]
33. Shin, K.-O.; Ha, D.H.; Kim, J.O.; Crumrine, D.A.; Meyer, J.M.; Wakefield, J.S.; Lee, Y.; Kim, B.; Kim, S.; Kim, H.-k.; et al. Exosomes
from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis
of Ceramides in Atopic Dermatitis. Cells 2020, 9, 680. [CrossRef] [PubMed]
34. Colletti, M.; Galardi, A.; De Santis, M.; Guidelli, G.M.; Di Giannatale, A.; Di Luigi, L.; Antinozzi, C. Exosomes in Systemic
Sclerosis: Messengers Between Immune, Vascular and Fibrotic Components? Int. J. Mol. Sci. 2019, 20, 4337. [CrossRef] [PubMed]
35. Sobolewski, P.; Maślińska, M.; Wieczorek, M.; Łagun, Z.; Malewska, A.; Roszkiewicz, M.; Nitskovich, R.; Szymańska, E.; Walecka,
I. Systemic sclerosis—Multidisciplinary disease: Clinical features and treatment. Reumatologia 2019, 57, 221–233. [CrossRef]
36. O’Reilly, S.; Cant, R.; Ciechomska, M.; van Laar, J.M. Interleukin-6: A new therapeutic target in systemic sclerosis? Clin. Transl.
Immunol. 2013, 2, e4. [CrossRef]
37. Quiñones-Vico, M.I.; Sanabria-de la Torre, R.; Sánchez-Díaz, M.; Sierra-Sánchez, Á.; Montero-Vílchez, T.; Fernández-González, A.;
Arias-Santiago, S. The Role of Exosomes Derived From Mesenchymal Stromal Cells in Dermatology. Front. Cell Dev. Biol. 2021, 9,
647012. [CrossRef]
38. Fang, S.; Xu, C.; Zhang, Y.; Xue, C.; Yang, C.; Bi, H.; Qian, X.; Wu, M.; Ji, K.; Zhao, Y.; et al. Umbilical Cord-Derived Mesenchymal
Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-
β/SMAD2 Pathway During Wound Healing. Stem Cells Transl. Med. 2016, 5, 1425–1439. [CrossRef]
39. Hu, Y.; Rao, S.S.; Wang, Z.X.; Cao, J.; Tan, Y.J.; Luo, J.; Li, H.M.; Zhang, W.S.; Chen, C.Y.; Xie, H. Exosomes from human umbilical
cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function.
Theranostics 2018, 8, 169–184. [CrossRef]
40. Vyas, K.S.; Kaufman, J.; Munavalli, G.S.; Robertson, K.; Behfar, A.; Wyles, S.P. Exosomes: The latest in regenerative aesthetics.
Regen. Med. 2023, 18, 181–194. [CrossRef]
41. Zhang, B.; Gong, J.; He, L.; Khan, A.; Xiong, T.; Shen, H.; Li, Z. Exosomes based advancements for application in medical
aesthetics. Front. Bioeng. Biotechnol. 2022, 10, 1083640. [CrossRef]
42. Lo Cicero, A.; Delevoye, C.; Gilles-Marsens, F.; Loew, D.; Dingli, F.; Guéré, C.; André, N.; Vié, K.; van Niel, G.; Raposo, G.
Exosomes released by keratinocytes modulate melanocyte pigmentation. Nat. Commun. 2015, 6, 7506. [CrossRef] [PubMed]
43. Wong, P.M.; Yang, L.; Yang, L.; Wu, H.; Li, W.; Ma, X.; Katayama, I.; Zhang, H. New insight into the role of exosomes in vitiligo.
Autoimmun. Rev. 2020, 19, 102664. [CrossRef] [PubMed]
44. McCabe, M.C.; Hill, R.C.; Calderone, K.; Cui, Y.; Yan, Y.; Quan, T.; Fisher, G.J.; Hansen, K.C. Alterations in extracellular matrix
composition during aging and photoaging of the skin. Matrix Biol. Plus 2020, 8, 100041. [CrossRef] [PubMed]
45. Oh, M.; Lee, J.; Kim, Y.J.; Rhee, W.J.; Park, J.H. Exosomes Derived from Human Induced Pluripotent Stem Cells Ameliorate the
Aging of Skin Fibroblasts. Int. J. Mol. Sci. 2018, 19, 1715. [CrossRef]
46. Zhong, Q.Y.; Lin, B.; Chen, Y.T.; Huang, Y.P.; Feng, W.P.; Wu, Y.; Long, G.H.; Zou, Y.N.; Liu, Y.; Lin, B.Q.; et al. Gender differences
in UV-induced skin inflammation, skin carcinogenesis and systemic damage. Environ. Toxicol. Pharmacol. 2021, 81, 103512.
[CrossRef] [PubMed]
47. Cooper, S.J.; Bowden, G.T. Ultraviolet B regulation of transcription factor families: Roles of nuclear factor-kappa B (NF-kappaB)
and activator protein-1 (AP-1) in UVB-induced skin carcinogenesis. Curr. Cancer Drug Targets 2007, 7, 325–334. [CrossRef]
[PubMed]
48. Varani, J.; Dame, M.K.; Rittie, L.; Fligiel, S.E.; Kang, S.; Fisher, G.J.; Voorhees, J.J. Decreased collagen production in chronologically
aged skin: Roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am. J. Pathol. 2006, 168,
1861–1868. [CrossRef]
49. Byron, A.; Humphries, J.D.; Humphries, M.J. Defining the extracellular matrix using proteomics. Int. J. Exp. Pathol. 2013, 94,
75–92. [CrossRef]
50. Li, L.; Ngo, H.T.T.; Hwang, E.; Wei, X.; Liu, Y.; Liu, J.; Yi, T.H. Conditioned Medium from Human Adipose-Derived Mesenchymal
Stem Cell Culture Prevents UVB-Induced Skin Aging in Human Keratinocytes and Dermal Fibroblasts. Int. J. Mol. Sci. 2019,
21, 49. [CrossRef]
51. Fafián-Labora, J.A.; Rodríguez-Navarro, J.A.; O’Loghlen, A. Small Extracellular Vesicles Have GST Activity and Ameliorate
Senescence-Related Tissue Damage. Cell Metab. 2020, 32, 71–86.e75. [CrossRef]
52. Tallant, C.; Marrero, A.; Gomis-Rüth, F.X. Matrix metalloproteinases: Fold and function of their catalytic domains. Biochim. Biophys.
Acta 2010, 1803, 20–28. [CrossRef] [PubMed]
53. Juhl, P.; Bondesen, S.; Hawkins, C.L.; Karsdal, M.A.; Bay-Jensen, A.-C.; Davies, M.J.; Siebuhr, A.S. Dermal fibroblasts have
different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis. Sci. Rep. 2020, 10, 17300.
[CrossRef] [PubMed]
54. Carrillo-Gálvez, A.B.; Gálvez-Peisl, S.; González-Correa, J.E.; de Haro-Carrillo, M.; Ayllón, V.; Carmona-Sáez, P.; Ramos-Mejía, V.;
Galindo-Moreno, P.; Cara, F.E.; Granados-Principal, S.; et al. GARP is a key molecule for mesenchymal stromal cell responses to
TGF-β and fundamental to control mitochondrial ROS levels. Stem Cells Transl. Med. 2020, 9, 636–650. [CrossRef]
Cosmetics 2023, 10, 65 14 of 14

55. Zhang, B.; Wu, X.; Zhang, X.; Sun, Y.; Yan, Y.; Shi, H.; Zhu, Y.; Wu, L.; Pan, Z.; Zhu, W.; et al. Human umbilical cord mesenchymal
stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway. Stem Cells Transl. Med. 2015, 4, 513–522.
[CrossRef]
56. Zhang, J.; Chen, C.; Hu, B.; Niu, X.; Liu, X.; Zhang, G.; Zhang, C.; Li, Q.; Wang, Y. Exosomes Derived from Human Endothelial
Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling. Int. J. Biol. Sci.
2016, 12, 1472–1487. [CrossRef] [PubMed]
57. Zhang, B.; Wang, M.; Gong, A.; Zhang, X.; Wu, X.; Zhu, Y.; Shi, H.; Wu, L.; Zhu, W.; Qian, H.; et al. HucMSC-Exosome
Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing. Stem Cells 2015, 33, 2158–2168. [CrossRef] [PubMed]
58. Dalirfardouei, R.; Jamialahmadi, K.; Jafarian, A.H.; Mahdipour, E. Promising effects of exosomes isolated from menstrual
blood-derived mesenchymal stem cell on wound-healing process in diabetic mouse model. J. Tissue Eng. Regen. Med. 2019, 13,
555–568. [CrossRef] [PubMed]
59. Wang, X.; Jiao, Y.; Pan, Y.; Zhang, L.; Gong, H.; Qi, Y.; Wang, M.; Gong, H.; Shao, M.; Wang, X.; et al. Fetal Dermal Mesenchymal
Stem Cell-Derived Exosomes Accelerate Cutaneous Wound Healing by Activating Notch Signaling. Stem Cells Int. 2019,
2019, 2402916. [CrossRef]
60. Picardo, M.; Dell’Anna, M.L.; Ezzedine, K.; Hamzavi, I.; Harris, J.E.; Parsad, D.; Taieb, A. Vitiligo. Nat. Rev. Dis. Prim. 2015,
1, 15011. [CrossRef]
61. Rashighi, M.; Harris, J.E. Vitiligo Pathogenesis and Emerging Treatments. Dermatol. Clin. 2017, 35, 257–265. [CrossRef]
62. Grymowicz, M.; Rudnicka, E.; Podfigurna, A.; Napierala, P.; Smolarczyk, R.; Smolarczyk, K.; Meczekalski, B. Hormonal Effects on
Hair Follicles. Int. J. Mol. Sci. 2020, 21, 5342. [CrossRef] [PubMed]
63. Shimizu, Y.; Ntege, E.H.; Sunami, H.; Inoue, Y. Regenerative medicine strategies for hair growth and regeneration: A narrative
review of literature. Regen. Ther. 2022, 21, 527–539. [CrossRef] [PubMed]
64. Li, Y.; Wang, G.; Wang, Q.; Zhang, Y.; Cui, L.; Huang, X. Exosomes Secreted from Adipose-Derived Stem Cells Are a Potential
Treatment Agent for Immune-Mediated Alopecia. J. Immunol. Res. 2022, 2022, 7471246. [CrossRef]
65. Kwack, M.H.; Seo, C.H.; Gangadaran, P.; Ahn, B.-C.; Kim, M.K.; Kim, J.C.; Sung, Y.K. Exosomes derived from human dermal
papilla cells promote hair growth in cultured human hair follicles and augment the hair-inductive capacity of cultured dermal
papilla spheres. Exp. Dermatol. 2019, 28, 854–857. [CrossRef] [PubMed]
66. Wu, J.; Yang, Q.; Wu, S.; Yuan, R.; Zhao, X.; Li, Y.; Wu, W.; Zhu, N. Adipose-Derived Stem Cell Exosomes Promoted Hair
Regeneration. Tissue Eng. Regen. Med. 2021, 18, 685–691. [CrossRef] [PubMed]

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