Received: 3 May 2023 | Revised: 29 June 2023 | Accepted: 3 July 2023

DOI: 10.1111/jocd.15930

ORIGINAL ARTICLE

A review of exosomes and their application in cutaneous

medical aesthetics

Kehinde Raji Olumesi MD, MPH | David J. Goldberg MD, JD

Skin Laser and Surgery Specialists-­A

Division of Schweiger Dermatology
Group, Hackensack, New Jersey, USA
Correspondence
David J. Goldberg, Skin Laser and Surgery
Specialists-­A Division of Schweiger
Dermatology Group, 20 Prospect Ave,
Suite 702, Hackensack NJ 07601, USA.
Email: david.goldberg@schweigerderm.
com
Abstract
Background: Exosomes have gained recent popularity in aesthetic medicine; how-
ever, there is still a dearth of understanding on the etiology of exosomes, their physi-
ologic function, and regenerative capabilities.
Objective: The purpose of this article is to summarize some of the physiologic func-
tions of exosomes, their mechanistic role, and current commercial landscape in regen-
erative aesthetics.
Methods: A Medline search was conducted with the keywords, exosomes, extracel-
lular vesicles, stem cells, skin rejuvenation, and cutaneous aesthetics. MeSH term “ex-
osomes” filtered by relevant subheadings was also utilized. Pertinent original articles
encompassing animal studies, cell studies, and human studies were included. We re-
stricted to articles published in the last 10 years.
Results: Pre-­clinical studies have demonstrated the therapeutic capabilities of ex-
osomes in wound healing, scar modulation, alopecia, and skin rejuvenation. Exosomes
primarily exert their effects in a paracrine function and modulate the interactions be-
tween keratinocytes and other cells of the skin. Exogenous exosomes can be utilized
in a variety of settings to bring about desired aesthetic outcomes and to date, has only
been approved for topical administration.
Conclusion: The safety, efficacy, potency, and dosages of exosomes remains to be
determined via robust human clinical trials. Isolation and purification techniques have
yet to be standardized, and this would be required for regulatory approval of all deliv-
ery modes. Overall, exosomes deliver yet another therapeutic option in regenerative
aesthetics.

KEYWORDS
dermatology, exosomes, stem cells, therapeutic, tissue regeneration

1 | I NTRO D U C TI O N
Exosomes are secreted extracellular vesicles (EVs) that contain
products of their predecessor cells to include RNA, DNA, proteins,
lipids, amino acids, and metabolites.1 All cells release EVs, and they
are found in all bodily fluids with exosomes being a subcategory that
is smaller and endosomal in origin.1,2 They are ~100 nm in diameter,
and their constituents suggest a role in cell-­to-­cell communication.1
Exosomes have been found to modify the biologic responses of re-
cipient cells based on the proteins, metabolites, and nucleic acids

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

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wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2023;22:2628–2634.

Flora Martinez - dra.floramartinez@gmail.com - IP: 201.88.48.64


OLUMESI and GOLDBERG
conveyed. These modifications either inhibit or stimulate disease
1
pathogenesis. These intrinsic properties have elevated the poten-
tial utilization of exosomes not only in the therapeutic control of
various pathogenesis, but also in the realm of cutaneous medical
aesthetics.
In the skin, it has been demonstrated that exosome-­mediated
cell-­to-­cell communication and transfer plays a role in tissue ho-
meostasis and maintenance of cellular function with a demonstrated
interplay in the pathophysiology of chronic inflammatory skin dis-
3,4
eases. In addition, extracellular vesicles released by mesenchymal
stem cells (MSCs-­E V) are noted to play a role in wound healing by
delivering proangiogenic, anti-­inflammatory, and antifibrotic proper-
ties, hence the recent introduction of exosomes derived from stem
2
cells in conditioned media into the skin rejuvenation space. Other
types of stem-­cell-­derived extracellular vesicles (SC-­E Vs) have also
been found to have a role in anti-­aging.5 For instance, exosomes
derived from human umbilical cord blood mesenchymal stem cells
(UCB-­MSCs) have been demonstrated to promote cell migration and
collagen synthesis of human dermal fibroblasts (HDFs).6 The same
group found that these UCB-­MSCs-­derived exosomes permeated
the skin layer and were found to increase the synthesis of collagen 1
and elastin, the major building blocks of skin rejuvenation.
The goal of this review is to provide a summary of the mech-
anistic role of exosomes in aesthetic medicine as it relates to skin
rejuvenation with a brief spotlight on wound healing and scar re-
modeling, as well as describe some of the existing and emerging
commercially available therapies. The objective is to provide the
novice dermatologist with an understanding of the mechanism and
therapeutic applications of exosomes in the cutaneous aesthetic
medicine. We performed a systematic literature review in Medline
utilizing the terms “exosomes in cutaneous aesthetics” and “exo-
some physiology.” In addition, the MeSH term “exosomes” along
with various subheadings to include chemistry, classification, drug
effects, metabolism, physiology, and ultrastructure were used to
build a PubMed search. Reference lists from included studies and
review articles were also perused to identify additional studies. We
limited to articles published in the last 10 years.
2 | E XOS O M E S I N S K I N R EG E N E R ATI O N
A N D R E PA I R
2.1 | Wound healing
Exosomes have been found to play a role in angiogenesis, cell pro-
liferation and differentiation, apoptosis, and inflammation, which
has led to a surging interest in their therapeutic potential in wound
healing.3,7 Exosomes derived from multiple sources, by modulating
effector cells, can regulate wound healing (Figure A1). Various nota-
ble sources include MSCs, keratinocytes, endothelial cells, immune
cells, and several body fluids.
In the skin, the complex interplay between the various cells
involved in wound healing to include keratinocytes, macrophage,
Flora Martinez - dra.floramartinez@gmail.com - IP: 201.88.48.64
|
14732165, 2023, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.15930 by UFMS - Fundacao Universidade Federal de Mato Grosso do Sul, Wiley Online Library on [23/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2629
endothelial cells, fibroblasts, adipocytes, and other cells of the im-
mune system have been found to be partially facilitated by skin-­cell-­
derived exosomes.3,8 For instance, mice studies found that injecting
M2 macrophage-­produced exosomes into skin wounds increased
M2 populations of macrophages which are anti-­inflammatory, lead-
ing to increased fibroblast migration, deposition of collagen and
endothelial cell stimulation, while decreasing M1 macrophage (pro-­
inflammatory) populations.3,9 Diabetic wound healing mice studies
also found that MSC-­derived exosomes, through secretion of proin-
flammatory cytokines and molecules, promoted angiogenesis and
proliferative effects.10 Mesoglycan a fibrinolytic compound recently
found to have promising effects in skin wound healing was investi-
gated by Belvedere et al. and demonstrated its ability to activate ke-
ratinocytes to produce extracellular vesicles, particularly exosomes.
In vitro assays of the secreted exosomes from these mesoglycan-­
treated keratinocytes demonstrated pro enhanced migration and
invasion of fibroblasts and endothelial cells.11
Exosomes derived from mesenchymal stem cells (MSCs-­E xos)
have been found to have better functionality and are easier to han-
dle than cell-­based products.12 They inhibit pro-­inflammatory cyto-
kines to promote anti-­inflammatory effects and enhance remodeling
of the extracellular matrix (ECM) to stimulate tissue regeneration.3,7
Furthermore, human bone-­marrow MSC (BMSCs)-­derived exosomes
were found to have promising potential in the acceleration of wound
healing via mice studies by inhibiting the transforming growth factor
beta (TGF-­B)/Smad signal pathway (Figure A1). Attenuation of this
pathway has been demonstrated in non-­healing wounds.13,14
3 | A PPLI C ATI O N O F E XOS O M E S I N S K I N
A E S TH E TI C S
Dermatologists are often faced with a plethora of various cosmetic
concerns. Scarring, skin aging, pigmentary alterations, and hair loss
are some of the more common concerns that dermatologists face in
their day-­to-­day practice. Exosomes serve as a robust therapeutic
option to simultaneously address a multitude of concerns given their
recent application in scar improvement therapies, pigmentation cor-
rection, skin rejuvenation, and hair loss recovery.
3.1 | Exosomes in scar remodeling
Scar formation is an essential, yet oftentimes undesired outcome
of cutaneous injury, whether accidental, pathological, or iatrogenic,
such as surgical scars. Mechanistically, various factors that potenti-
ate scar formation include increased collagen deposition, decreased
fibroblast apoptosis, protracted inflammation, excessive angiogen-
esis, augmented TGF-­B1 expression, and delayed keratinocyte func-
tion.3 Exosomes have been found to the involved in the intercellular
communication required for scar formation.15 Several studies have
investigated the action of exogenous exosomes derived from vari-
ous sources on scar formation.
 |
2630
One study investigated the systemic administration of exo-
somes derived from adipose mesenchymal stem cells (ASCs-­E xos)
in mice wound models. They found that while early wound heal-
ing stages were characterized by increased collagen I and III, later
stages demonstrated reduced scar formation leading them to be-
lieve that the ASC-­E xos downregulated collagen expression at this
time point.16 Another study found that remodeling of the extracel-
lular matrix (ECM) via intravenous administration of ASC-­E xos was a
key component of achieving a scarless wound repair.17 Furthermore,
exosomes derived from human induced pluripotent stem-­
cell-­
derived mesenchymal stem cells (hiPSC-­MSCs-­E xos) were found to
enhance re-­epithelization, angiogenesis, collagen maturity, and led
to reduced scar widths.18 Exosomes from menstrual-­blood derived
MSCs were found to increase neoangiogenesis and accelerate re-­
epithelization of wounds in diabetic mice models, leading to reduced
scar formation (Figure A1).19 The exosomes from umbilical cord-­
derived MSCs (uMSCs-­exos) were found to suppress the differen-
tiation and excessive aggregation of myofibroblasts, subsequently
leading to reduced fibrosis and scar development (Figure A1).3
Overall, these findings indicate that exosomes from various
sources have a key role in regulating fibroblast function and col-
lagen remodeling or deposition to promote reduced scar forma-
tion. Exosomes are therefore a promising therapeutic approach
to not only enhancement of wound healing but also possible scar
prevention.
3.2 | Exosomes in skin rejuvenation
The effects and appearance of the aged skin are one of the more
common reasons for seeking dermatologic cosmetic consultation.
Both internal and external factors contribute to skin aging to include
UV radiation, air pollution, and behavioral choices such as smoking
and tanning. Photodamage, in particular, leads to changes in the
ECM to include decreased collagen and elastic fibers, leading to the
clinical appearances of wrinkles, coarseness, dryness, and sallow
20,21
skin texture. Overall, skin aging is characterized by degradation
of skin matrix by metalloproteinases (MMPs) and reduced fibroblast
16
function, hence reduced collagen formation and restoration.
Exosomes, in their ability to modulate cell–­cell communication
and some functions of fibroblasts, have gained a lot of attention
and potential therapeutic utility in skin rejuvenation in recent years.
One study examining the utility of transdermal delivery of exosomes
derived from three-­dimensional spheroids of HDFs discovered an
increase in procollagen type 1 and decreased MMP-­1 expression
22
(Figure A1). Another study investigated the effect that application
of exosomes derived from human induced pluripotent stem cells
(iPSCs-­E xos) had on UVB irradiated (aged) HDFs. 23 Authors found
that pretreatment with the iPCS-­E xos impeded damage to the HDFs,
decreased overexpression of MMP, and restored collagen type 1 ex-
pression.3,5 Furthermore, exosomes derived from embryonic stem
cells were found to have the ability to reverse fibroblast senescence
by regulating the TGF-­B receptor 2 pathway (Figure A1). 22 These
Flora Martinez - dra.floramartinez@gmail.com - IP: 201.88.48.64
14732165, 2023, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.15930 by UFMS - Fundacao Universidade Federal de Mato Grosso do Sul, Wiley Online Library on [23/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
OLUMESI and GOLDBERG
properties have led to the recent introduction of various commer-
cially available stem cell-­derived extracellular vesicles in the skin
rejuvenation space.
4 | CU R R E NT TH E R A PEU TI C A N D
CO M M E RC I A L L A N DS C A PE O F
E X TR AV E S I CU L A R V E S I C LE S ( E V )
There is yet to be FDA clearance for any injectable exosome therapy,
and current use in dermatologic practice is confined to topical ap-
plication. This is sometimes done in conjunction with micro-­needling
or laser therapy to enhance penetration. It is possible that injected
exosomes will be regulated as drugs and biological products under
section 351 of public Health Service (PHS) Act and the Federal Food
Drug & Cosmetics (FD&C) Act, although to our knowledge, no pub-
lications on specific regulatory guidelines exist. 24 The above guide-
lines would require that studies demonstrate safety, efficacy, purity,
and potency of their specific product. 25 It is therefore important for
practitioners to implement caution when utilizing injected exosomes
as adjunctive therapies.
What is also clear is that the efficacy of pre-­clinical studies, and
some clinical data, has highlighted the significant commercial poten-
tial of EV/exosomes therapy. Currently, over 30 international com-
panies have EV products in the research and development phase. 24
Three main categories are included: EVs of cellular origin (typically
stem cells), engineered EVs (cell source genetically modified to over-
express the therapeutic component of interest), and fusion systems,
in which EVs are combined with synthetic lipid nanoparticles. 24
Several EV products currently undergoing research and devel-
opment for chronic wound healing and inflammatory skin conditions
are summarized in the included Table. One example is ExoWound by
Exogenus Therapeutics, a combination of EVs derived from human
umbilical cord blood mononuclear cells with a slow-­release hydrogel.
Topical application of this product to wound in diabetic mice models
led to accelerated wound closure. 26,27 Another allogenic EV product
(Syngenus) being developed by Regenus also delivered via hydrogel
is being studied in the management of acne. 24
Another notable exosome product developed by BENEV Inc., in
partnership with ExoCobio (Table A1) demonstrated improvement/
reversal of the aging process through mice studies in which small
EVs (sEVs) from adipose MSCs (ADSC-­sEVs) from young mice were
injected into older mice. 28 An improvement in motor coordination,
grip strength, fatigue-­resistance, fur regeneration, and renal func-
tion was demonstrated. Furthermore, a notable decrease in oxidate
stress, inflammation, and senescence markers was noted. 28 This
exosome regenerative complex is now marketed for post-­procedure
topical application for the management of hair loss, skin aging, and
dyspigmentation.
Combination of EVs with over-­the-­counter moisturizers and se-
rums is a growing trend in the commercial space with the exosomes
in these formulations primarily derived from adult human stem
cells. 24 Doses of extracellular vesicles in these products are difficult

OLUMESI and GOLDBERG
to ascertain. One product Zen, developed by Exoskin Simple, was
24
found to have 500 000 EVs per mL. In contrast, the products mar-
keted for clinical applications, primarily containing adult or neonatal
stem cell-­derived exosomes, were developed to deliver between 1
and 25 billion EVs (Table A1). 24 Information on how companies de-
fine EVs in their products is often ambiguous. 29
Overall, these available products are formulated for topical ad-
ministration or in combination procedures to enhance delivery such
as micro-­needling or laser treatments.
5 | LI M ITATI O N S
Exosomes are an emerging powerhouse in cutaneous medical aes-
thetics. Their multifunctionality has proven exceedingly promising
in expanding therapeutic options for various pathologies. However,
there are various limitations to consider and address for widespread,
homogenous utilization in clinical practice to occur.
Currently, no standardized protocol for the isolation, storage,
or identification of exosomes exists. The sourcing and isolation,
purification, and identifications of exosomes are widely heterog-
enous and their specific mechanisms of actions remains mostly
unclear. For instance, several isolation techniques described in-
clude ultracentrifugation, size-­
b ased filtration, size-­
e xclusion
chromatography, polymer precipitation, and novel combination
techniques. 3,7
Another limitation is that pre-­clinical studies of mice and animal
while showing promising effects may not necessarily translate to
clinical application due to a difference in physiological and patholog-
ical processes. Human clinical trials are just beginning to determine
true safety and efficacy.
6 | CO N C LU S I O N
The therapeutic potential of exosomes in dermatology is wide and
varied. From inflammatory skin conditions to cosmetic concerns,
exosome use opens up a whole new avenue of management options
for clinicians.30
C O N FL I C T O F I N T E R E S T S TAT E M E N T
No conflicts of interest.
DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable to this article as no new data were cre-
ated or analyzed in this study.
E T H I C S S TAT E M E N T
The authors confirm that the ethical policies of the journal, as noted
on the journal’s author guideline, have been adhered to. Since this
article is a review of the medical literature and no subjects have been
treated, the issue of informed consent is not relevant.
Flora Martinez - dra.floramartinez@gmail.com - IP: 201.88.48.64
|
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2631
ORCID
David J. Goldberg https://orcid.org/0000-0002-8950-439X
REFERENCES
1. Kalluri R, LeBleu VS. The biology, function,and biomedical ap-
plications of exosomes. Science. 2020;367(6478):eaau6977.
doi:10.1126/science.aau6977
2. Yin L, Liu X, Shi Y, et al. Therapeutic advances of stem cell-­derived
extracellular vesicles in regenerative medicine. Cell. 2020;9(3):707.
doi:10.3390/cells9030707
3. Xiong M, Zhang Q, Hu W, et al. The novel mechanisms and ap-
plications of exosomes in dermatology and cutaneous medi-
cal aesthetics. Pharmacol Res. 2021;166:105490. doi:10.1016/j.
phrs.2021.105490
4. Wang WM, Wu C, Jin HZ. Exosomes in chronic inflammatory
skin diseases and skin tumors. Exp Dermatol. 2019;28(3):213-­218.
doi:10.1111/exd.13857
5. Oh M, Lee J, Kim YJ, Rhee WJ, Park JH. Exosomes derived from
human induced pluripotent stem cells ameliorate the aging of
skin fibroblasts. Int J Mol Sci. 2018;19(6):1715. doi:10.3390/
ijms19061715
6. Kim YJ, Yoo SM, Park HH, et al. Exosomes derived from human um-
bilical cord blood mesenchymal stem cells stimulates rejuvenation
of human skin. Biochem Biophys Res Commun. 2017;493(2):1102-­
1108. doi:10.1016/j.bbrc.2017.09.056
7. Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of
the isolation, characterization, biological function, and multifar-
ious therapeutic approaches of exosomes. Cells. 2019;8(4):307.
doi:10.3390/cells8040307
8. Çankirili NK, Altundag O, Çelebi-­Saltik B. Skin stem cells, their
niche and tissue engineering approach for skin regeneration. Adv
Exp Med Biol. 2020;1212:107-­126. doi:10.1007/5584_2019_380
9. Kim H, Wang SY, Kwak G, Yang Y, Kwon IC, Kim SH. Exosome-­
guided phenotypic switch of M1 to M2 macrophages for cutaneous
wound healing. Adv Sci (Weinh). 2019;6(20):1900513. doi:10.1002/
advs.201900513
10. Li M, Wang T, Tian H, Wei G, Zhao L, Shi Y. Macrophage-­
derived exosomes accelerate wound healing through their anti-­
inflammation effects in a diabetic rat model. Artif Cells Nanomed
Biotechnol. 2019;47(1):3793-­3803. doi:10.1080/21691401.2019.16
69617
11. Belvedere R, Pessolano E, Porta A, et al. Mesoglycan induces the
secretion of microvesicles by keratinocytes able to activate human
fibroblasts and endothelial cells: a novel mechanism in skin wound
healing. Eur J Pharmacol. 2020;15(869):172894. doi:10.1016/j.
ejphar.2019.172894
12. Marote A, Teixeira FG, Mendes-­Pinheiro B, Salgado AJ. MSCs-­
derived exosomes: cell-­ secreted Nanovesicles with regener-
ative potential. Front Pharmacol. 2016;3(7):231. doi:10.3389/
fphar.2016.00231
13. Jiang T, Wang Z, Sun J. Human bone marrow mesenchymal stem
cell-­derived exosomes stimulate cutaneous wound healing medi-
ates through TGF-­β/Smad signaling pathway. Stem Cell Res Ther.
2020;11:198. doi:10.1186/s13287- ­020- ­01723-­6
14. Ramirez H, Patel SB, Pastar I. The role of TGFβ signaling in wound
epithelialization. Adv Wound Care (New Rochelle). 2014;3(7):482-­
491. doi:10.1089/wound.2013.0466
15. Chen J, Zhou R, Liang Y, Fu X, Wang D, Wang C. Blockade of
lncRNA-­A SLNCS5088-­enriched exosome generation in M2 mac-
rophages by GW4869 dampens the effect of M2 macrophages on
orchestrating fibroblast activation. FASEB J. 2019;33(11):12200-­
12212. doi:10.1096/fj.201901610
16. Hu L, Wang J, Zhou X, et al. Exosomes derived from human ad-
ipose mensenchymal stem cells accelerates cutaneous wound
 |
2632
healing via optimizing the characteristics of fibroblasts. Sci Rep.
2016;12(6):32993. doi:10.1038/srep32993
17. Wang L, Hu L, Zhou X, et al. Exosomes secreted by human adipose
mesenchymal stem cells promote scarless cutaneous repair by reg-
ulating extracellular matrix remodelling. Sci Rep. 2017;7(1):13321.
doi:10.1038/s41598-­017-­12919-­x
18. Zhang J, Guan J, Niu X, et al. Exosomes released from human in-
duced pluripotent stem cells-­derived MSCs facilitate cutaneous
wound healing by promoting collagen synthesis and angiogenesis. J
Transl Med. 2015;1(13):49. doi:10.1186/s12967-­015-­0 417-­0
19. Dalirfardouei R, Jamialahmadi K, Jafarian AH, Mahdipour E.
Promising effects of exosomes isolated from menstrual blood-­
derived mesenchymal stem cell on wound-­healing process in dia-
betic mouse model. J Tissue Eng Regen Med. 2019;13(4):555-­568.
doi:10.1002/term.2799
20. Davinelli S, Bertoglio JC, Polimeni A, Scapagnini G. Cytoprotective
polyphenols against chronological skin aging and cutaneous
Photodamage. Curr Pharm des. 2018;24(2):99-­105. doi:10.2174/13
81612823666171109102426
21. Tigges J, Krutmann J, Fritsche E, et al. The hallmarks of fibro-
blast ageing. Mech Ageing Dev. 2014;138:26-­4 4. doi:10.1016/j.
mad.2014.03.004
22. Hu S, Li Z, Cores J, et al. Needle-­free injection of exosomes de-
rived from human dermal fibroblast spheroids ameliorates skin
Photoaging. ACS Nano. 2019;13(10):11273-­11282. doi:10.1021/
acsnano.9b04384
23. Bae YU, Son Y, Kim CH, et al. Embryonic stem cell-­d erived
mmu-­m iR-­2 91a-­3 p inhibits cellular senescence in human dermal
fibroblasts through the TGF-­β receptor 2 pathway. J Gerontol
A Biol Sci Med Sci. 2019;74(9):1359-­1367. doi:10.1093/gerona/
gly208
24. Davies OG, Williams S, Goldie K. The therapeutic and com-
mercial landscape of stem cell vesicles in regenerative derma-
tology. J Control Release. 2023;353:1096-­1106. doi:10.1016/j.
jconrel.2022.12.025
25. Ilic N, Savic S, Siegel E, Atkinson K, Tasic L. Examination
of the regulatory frameworks applicable to biologic drugs
Flora Martinez - dra.floramartinez@gmail.com - IP: 201.88.48.64
14732165, 2023, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.15930 by UFMS - Fundacao Universidade Federal de Mato Grosso do Sul, Wiley Online Library on [23/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
OLUMESI and GOLDBERG
(including stem cells and their progeny) in Europe, the U.S., and
Australia: part II –­ a method of software documentary analy-
sis. Stem Cells Transl Med. 2012;1(12):909-­9 20. doi:10.5966/
sctm.2012-­0 038
26. Cardoso RMS, Rodrigues SC, Gomes CF, et al. Development of an
optimized and scalable method for isolation of umbilical cord blood-­
derived small extracellular vesicles for future clinical use. Stem Cells
Transl Med. 2021;10(6):910-­921. doi:10.1002/sctm.20-­0376
27. Rodrigues SC, Cardoso RMS, Freire PC, et al. Immunomodulatory
properties of umbilical cord blood-­ d erived small extracellu-
lar vesicles and their therapeutic potential for inflammatory
skin disorders. Int J Mol Sci. 2021;22(18):9797. doi:10.3390/
ijms22189797
28. Sanz-­Ros J, Romero-­García N, Mas-­Bargues C, et al. Small extracel-
lular vesicles from young adipose-­derived stem cells prevent frailty,
improve health span, and decrease epigenetic age in old mice. Sci
Adv. 2022;8(42):eabq2226. doi:10.1126/sciadv.abq2226
29. Bai Y, Han YD, Yan XL, et al. Adipose mesenchymal stem cell-­
derived exosomes stimulated by hydrogen peroxide enhanced
skin flap recovery in ischemia-­ reperfusion injury. Biochem
Biophys Res Commun. 2018;500(2):310-­317. doi:10.1016/j.
bbrc.2018.04.065
30. Zhao G, Liu F, Liu Z, et al. MSC-­derived exosomes attenuate cell
death through suppressing AIF nucleus translocation and enhance
cutaneous wound healing. Stem Cell Res Ther. 2020;11(1):174.
doi:10.1186/s13287-­020-­01616-­8\
How to cite this article: Olumesi KR, Goldberg DJ. A review of
exosomes and their application in cutaneous medical
aesthetics. J Cosmet Dermatol. 2023;22:2628-2634.
doi:10.1111/jocd.15930
 APPENDIX

TA B L E A 1 Commercially available EV formulation for clinical application use.

Company Product EV source EV dose Therapeutic effects Application

Exocel Bio, USA Exovex Revive Placental MSC a-­derived 5 billion/1 mL Modulation of macrophages involved in Skin
inflammatory initiation and resolution24 Skin
Exovex Renew 12 billion/2.5 mL
OLUMESI and GOLDBERG

Exovex Reveal 25 billion/5 mL Skin, neck, décolleté

ExoCoBio, South Korea ASCEb + Derma Signal Human adipose MSC a-­ 5 billion Reduces local levels I inflammatory cytokines and Skin
SRLV1c derived, lyophilized induced de novo production of ceramides24
ASCEb + Scalp Care HRLVd 10 billion Scalp
(ExoSCTR™)e Replenish skin barrier
Exomage TFf skin barrier 15% exosomes
ampoule
Infusio, Germany N/A Placental MSCsa ≥15 billion per treatment Based on demonstrated principle of anti-­aging in Anti-­aging/rejuvenation

Flora Martinez - dra.floramartinez@gmail.com - IP: 201.88.48.64

mice models that found that infusion of EVs
from plasma young mice led to increase lifespan
of older mice28
Kimera Exosomes, USA XoGlo® Perinatal MSC a-­derived 1 billion/mL No cellular or molecular evidence of soft tissue Skin
regeneration was provided
Regen Suppliers ReBellaXO™ Wharton's jelly-­derived 15 billion/mL Information difficult to ascertain Soft tissue, hair, facial
a
Direct Biologics, USA XoFlow™ Bone marrow MSC -­derived >10 billion/mL Information difficult to ascertain Wound healing, hair,
(allogenic) aesthetics
Benev, USA Exosome Regenerative MSC a-­derived, lyophilized 2.5 billion Information difficult to ascertain Skin
complex + powered by
ExoSCRT™
Exosome Regenerative 5 billion Skin and Scalp
complex + powered by
ExoSCRT™
AnteAgeMD, USA AnteAge® with Stem Bone-­marrow MSC a-­derived Not readily available Information difficult to ascertain Skin, hair
Cytokines
Vitti Labs, USA Vitti Cosmetics Cryo Elixir Placental MSC a-­derived Not readily available Skin rejuvenation
Elevai Labs Inc, USA ELEVAI empower Human umbilical Not readily available Anti-­inflammatory and wound healing effects Skin recovery
Elevai enfinity MSC a-­derived Skin rejuvenation
a
Mesenchymal stem cells.
b
Advanced Skin Care Complex from ExoCoBio.
c
Skin Rejuvenation Lyophilized Vehicle.
d
Hair Rejuvenation Lyophilized Vehicle.
e
|

Moniker for the patented purification method by which ExoCoBio separates and refines 0.1% pure exosomes from stem cell conditioned media and lyophilizes it to maximize stability before freeze drying.
f
Triple Function.
2633

14732165, 2023, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.15930 by UFMS - Fundacao Universidade Federal de Mato Grosso do Sul, Wiley Online Library on [23/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
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14732165, 2023, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.15930 by UFMS - Fundacao Universidade Federal de Mato Grosso do Sul, Wiley Online Library on [23/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2634 OLUMESI and GOLDBERG

F I G U R E A 1 Summarized mechanism of exosome regulation in wound healing, scar remodeling, and skin rejuvenation. mRNAs from
saliva-­derived exosomes were demonstrated to mediate proliferation, migration, and angiogenesis in in vitro studies of human umbilical
endothelial cells (HUVECs) leading to accelerated wound healing. Bone marrow MSCs (BMSCs)-­derived exosomes promoted keratinocyte
and fibroblasts proliferation in mice studies as well as decreased apoptosis and inflammation of fibroblasts demonstrating potential for
accelerating wound healing. Human amnion MSCs increased migration of epidermal cells. ASC-­E xos increased tube formation of HUVECs
and capillary density in skin flap neovascularization studies. Umbilical cord-­derived exosomes inhibited differentiation fibroblasts to
myofibroblasts leading to decreased scar formation. Skin rejuvenation characterized by increased collagen and elastin synthesis, improved
keratinocytes and fibroblast function, antisenescence of HDFs, and changes in genotype and phenotype of UVB-­irradiated HDFs were
modulated by 3D-­cultured HDFs, keratinocyte-­derived exosomes, embryonic stem cells, and human-­induced pluripotent stem cells (iPSCs).

Flora Martinez - dra.floramartinez@gmail.com - IP: 201.88.48.64