Received: 2 March 2023 | Revised: 30 May 2023 | Accepted: 4 June 2023

DOI: 10.1111/jocd.15869

REVIEW ARTICLE

Systematic review of exosome treatment in hair restoration:

Preliminary evidence, safety, and future directions

Aditya K. Gupta MD PhD1,2 | Tong Wang MSc2 | Jeffrey A. Rapaport MD3

1
Department of Medicine, Division of
Dermatology, University of Toronto, Abstract
Toronto, Ontario, Canada
Background: Exosomes are small extracellular vesicles with potential roles in modu-
2
Mediprobe Research Inc., London,
Ontario, Canada
lating the hair growth cycle and are an emerging therapy for patients with alopecia. In
3
Rapaport Hair Institute, Englewood recent years, researchers have made significant progress in deciphering the network
Cliffs, New Jersey, USA of cellular interactions and signaling pathways mediated by the transfer of exosomes.
Correspondence This has opened the door to a wide range of potential therapeutic applications with
Aditya K. Gupta, Mediprobe Research Inc., an increasing focus on its application in precision medicine.
645 Windermere Road, London, ON N5X
2P1, Canada. Aim: To evaluate current published evidence, both preclinical and clinical, on the use
Email: [email protected] of exosomes for hair restoration.
Methods: In January 2023, a systematic search was conducted using PubMed,
Embase, and the Cochrane Library. Records were identified, screened, and assessed
for eligibility as per the PRISMA guideline.
Results: We identified 16 studies (15 preclinical and 1 clinical) showing varying de-
grees of efficacy using exosomes derived from sources including adipose-­derived
stem cells (ADSCs) and dermal papilla cells (DPCs). Applications of exosomes isolated
from ADSCs (ADSC-­Exo) and DPCs have shown early promising results in preclini-
cal studies corroborated by results obtained from different model systems. Topical
ADSC-­Exo has been tried successfully in 39 androgenetic alopecia patients demon-
strating significant increases in hair density and thickness. No significant adverse re-
actions associated with exosome treatment have been reported thus far.
Conclusions: Although current clinical evidence supporting the use of exosome treat-
ment is limited, there is a growing body of evidence suggesting its therapeutic po-
tential. Further studies are warranted to define its mechanism of action, optimize its
delivery and efficacy, and to address important safety concerns.

KEYWORDS
alopecia, exosomes, hair, regenerative medicine

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.

2424 | 
wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2023;22:2424–2433.
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GUPTA et al. 2425

1 | I NTRO D U C TI O N well as any observed genotypic and/or phenotypic effects are sum-
marized in Table 1; each data entry was sorted based on the model
Hair loss attributed to non-­scarring alopecia, such as androgenetic system used (i.e., in vitro, in vivo, or ex vivo). Results from 1 clinical
alopecia (AGA) or alopecia areata (AA), represents a significant study of 39 patients are summarized in Table 2. No randomized or
source of disease and psychological burden to patients of all ages.1,2 controlled trials were found.
There is a need for new and innovative therapies that offer sustained
hair regrowth over extended durations with minimal side effects.
Previous studies have shown the potential efficacy of stem cell 3.1 | Preclinical evidence
therapies derived from the adipose tissue in inducing significant hair
growth in AGA and AA patients; similar results were also observed Favorable effects have been observed using exosomes derived from
using extract of secreted proteins containing exosome and other ex- a variety of cell types, this includes exosomes derived from mes-
tracellular vesicles (EVs).3,4 enchymal stem cells such as adipose-­derived stem cells (ADSCs)
Exosomes are small (30–­150 nm) cargo-­delivering EVs that mediate observed to increase hair growth and dermis thickness in vivo,
intercellular communications, they are characterized by a phospholipid potentially through paracrine regulation of DPCs as demonstrated
bilayer with specific surface markers and cargos that affect cell signal- in vitro (Table 1).10–­12,19 Similar functions were observed for DPC-­
ing and gene expression (e.g., cytokines, growth factors and regula- Exos; most notably, DPC-­E xos purified from three-­dimensional cell
tory microRNAs [miRNAs]).5 Although its exact mechanism of action culture induced human hair follicle growth (Table 1).13 This result
is unclear; it is suspected that exosomes, through modulations of para- corroborated findings of previous in vivo studies demonstrating
crine signaling, can mediate the crosstalk between epithelial cells and hair growth effects including the acceleration of the telogen-­to-­
mesenchymal cells during the hair growth cycle.6 For example, exo- anagen transition in mice, potentially through the upregulation of
somes derived from dermal papilla cells (DPCs; DPC-­Exos) were shown fibroblast growth factor and β-­catenin pathways.7,13,20 DPCs may
to upregulate the Wnt/β-­catenin pathway in outer root sheath cells function as a paracrine regulator of hair follicle stem cells (HFSCs)
(ORSCs), resulting in the telogen-­to-­anagen transition in mice.7 and ORSCs.7,13–­15 Interestingly, another in vitro study showed that
The present review covers the current landscape of exosome treat- exosomes isolated from human ORSCs exhibited similar effects vice
ment in hair restoration, with a focus on preclinical, clinical, and safety versa in DPCs (Table 1).17
data reported thus far in the literature. Issues concerning the safety of Other potential sources of exosomes include myeloid-­derived
exosome treatment, as well as future directions, are discussed. suppressor cells and amniotic fluid stem cells (Table 1). 21,22
Exosomes purified from platelet lysis or platelet-­rich plasma (PRP)
did not appear to be effective in vitro.12,17 The addition of fisetin (a
2 | M ATE R I A L S A N D M E TH O DS plant extract), as well as the use of bovine colostrum as an alterna-
tive exosome source, may increase the production of exosomes in
An electronic search was conducted in January 2023 using PubMed, cell culture systems (Table 1).16,18 Moreover, the use of a micronee-
Embase (Ovid), and the Cochrane Library, without date or language dle patch loaded with exosomes may improve the efficacy of topical
restrictions. We aimed to investigate published evidence pertaining formulations (Table 1). 23
to the use of exosomes for hair growth. Items identified using the Regulation of the hair growth cycle observed in preclinical stud-
following search/MeSH terms were combined: “exosome,” “alope- ies may be attributed to the delivery of miRNAs, which are short
cia,” “hair follicle,” “dermal papilla cell,” “root sheath,” and “Wnt path- strands of non-­coding RNA molecules with regulatory functions in
way.” Reference sections of relevant review articles were screened gene expression (Figure 2). Variable effects, such as promoting or
for additional records. Deduplication and screening of identified inhibiting hair growth, can be seen depending on the type of miRNA
records were performed using Rayyan (https://www.rayyan.ai/). delivered. A previous in vitro study reported migration of DPCs to
Studies were excluded if a mixture of EVs was used, and if the ob- the proximity of HFSCs during the telogen phase, which led to the
served effects could not be attributed to the exosome fraction; for uptake of CD63+ DPC-­E xos. 25 Sequencing analysis of DPC-­E xos
instance, studies examining the effects of nanovesicles produced identified 111 differentially expressed miRNAs, with miR-­22-­5p ex-
through serial cell protrusions were excluded as it may contain cel- hibiting inhibitory effects on hair growth through the downregula-
lular organelles and proteins not associated with exosomes.8 This tion of the LEF1 gene. 25 In contrast, miR-­181a-­5p and miR-­218-­5p
review was designed in concordance with the PRISMA guideline.9 found in DPC-­E xos were shown to induce hair growth in vitro and in
vivo, respectively (Table 1; Figure 2).14,20

3 | R E S U LT S A N D D I S CU S S I O N
3.2 | Clinical evidence
Following the initial identification of 255 search results, 16 articles
were eligible for data extraction (Figure 1). Of the 15 preclinical Exosomes are currently not approved by the U.S. Food and Drug
studies, information on source, content and target of exosomes, as Administration (FDA) to treat hair disorders. In a case series, records
 |

14732165, 2023, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.15869 by CAPES, Wiley Online Library on [06/05/2024]. 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
2426 GUPTA et al.

F I G U R E 1 Overview of the systematic search. CENTRAL, Cochrane Central Register of Controlled Trials.

of 39 AGA patients with mild to moderate hair loss who received 3.3 | Safety
exosome treatment were reviewed (Table 2). 24 Exosomes purified
from ADSCs were applied topically (>6 × 1010 particles/vial); each There is scarce information on the safety of exosome treatment in
application was administered with a microneedle roller once weekly patients experiencing hair loss. Safety data on topical exosome treat-
24
for 12 weeks. At follow-­up, significant improvements in hair den- ment are available from two studies of 39 AGA patients and 25 pa-
sity (146.6 hairs/cm2 vs. 121.7 hairs/cm2) and hair thickness (61.4 μm tients treated for acne scars.24,27 No serious adverse reactions were
vs. 52.6 μm) were observed. There were no age-­or hair loss duration-­ reported in AGA patients after exosomes derived from ADSCs were
dependent effects on treatment response. However, the possibility applied topically once weekly for a total of 12 treatment sessions
of spontaneous hair regrowth could not be excluded in this study (Table 2).24 In another double-­blinded study, 25 patients with acne
due to lack of control. scars were randomized to receive topical applications of either a 30%
Nonetheless, these results corroborated the findings of another gel of ADSC-­Exo or a control gel.27 Treatment was given twice a day
case series study using intradermal biologic injection containing for 2 days. At follow-­up, symptoms including pain, erythema, edema,
26
EVs. After one course of treatment, 64.5% (20/31) of patients and dryness were reported with both ADSC-­Exo treatment and con-
reported hair growth at follow-­up; trichoscan assessment in 11 re- trol, which resolved within 5 days.27 An average downtime of 4.1 days
sponders showed an increase in hair density between 11.1% and was associated with topical ADSC-­Exo treatment, which was signifi-
24.2%. 26 However, the effects observed in this study can not be cantly shorter compared with patients who received the control gel
attributed to the exosome fraction as the patients had received (4.3 days); one case of mild hyperpigmentation was also reported.27
injections containing a mixture of EVs. Another open-­label, single-­ The safety of subcutaneous injections was assessed in a case
arm study examining the effects of placental mesenchymal cell–­ series of 31 AGA patients who received biologic treatment derived
derived exosomes in alopecia patients is ongoing (Clini​calTr​ials.gov; from human bone marrow mesenchymal stem cells (MSCs), which
NCT05658094). contains a mixture of EVs in addition to exosomes. 26 Patients were
 TA B L E 1 Summary of preclinical evidence on the use of exosomes in hair restoration.

Source Content Target Observed genotypic effects Observed phenotypic effects Ref.
GUPTA et al.

In vitro results
ADSC -­ DPC • Downregulation of miR-­22 and • Increase in cell proliferation and migration [10]
TNF-­α signaling pathways • Protection against H2O2-­induced apoptosis
-­ DPC • Upregulation of β-­c atenin and • Increase in cell proliferation and migration [11]
MMP3 • Increase in the number of Ki67+ cells
• Increase in protein levels of β-­c atenin and MMP3
-­ DPC • Upregulation of hair follicle • Increase in cell proliferation and migration [12]
inductivity markers (ALP, versican,
and α-­SMA)
DPC -­ DPC • Upregulation of growth factors • Increase in cell proliferation [13]
(IGF-­1, KGF, and HGF) • Increase in secretion of growth factors (IGF-­1, KGF, and HGF)
miR-­181a-­5p HFSC • Downregulation of WIF1 and • Increase in cell proliferation [14]
SFRP2 • Protection against apoptosis
• Upregulation of Wnt/β-­c atenin
signaling pathway (BCL2, CCND1,
CTNNB1, and LEF1)
-­ HFSC • Upregulation of Wnt/β-­c atenin • Increase in cell proliferation [15]
signaling pathway • Protection against apoptosis
-­ ORSC -­ • Increase in cell proliferation and migration [7]
• Increase in protein levels of β-­c atenin and Shh
-­ ORSC • Upregulation of apoptosis regulator • Increase in cell proliferation [13]
(bcl2)
• Downregulation of apoptosis
regulator (bax)
HaCaT cella -­ HFSC • Upregulation of Wnt/β-­c atenin • Nuclear translocation of β-­c atenin [16]
signaling pathway (AXIN2) • Increase in the number of Ki67+ cells
• Increase in mitochondria activation (TOMM20+ cells)
• Increase in the number of cells with active mitochondria
HHORSC -­ DPC • Upregulation of hair follicle • Increase in cell viability, proliferation and migration [17]
inductivity markers (ALP, versican,
and α-­SMA)
PL -­ DPC • No or minimal change in hair follicle • Decrease in cell viability and proliferation [17]
inductivity markers (ALP, versican,
and α-­SMA)
PRP -­ DPC • No or minimal change in hair follicle • No or minimal change in cell proliferation [12]
inductivity markers (ALP, versican,
α-­SMA)
| 2427

(Continues)

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 TA B L E 1 (Continued)
| 2428

Source Content Target Observed genotypic effects Observed phenotypic effects Ref.

Bovine colostrum -­ DPC -­ • Increase in cell proliferation [18]

• Protection against the inhibitory effects of DHT on cell proliferation
• Increased protein level of β-­c atenin
In vivo results
ADSC -­ C57BL/6 mice • Upregulation of Wnt/β-­c atenin • Improved hair growth [10,11]
signaling pathway (WNT3A, AXIN2) • Increase in hair follicle count and dermis thickness
• Downregulation of SFRP1 • Increase in the protein level of β-­c atenin
• Loading of exosomes onto a microneedle patch improved hair coverage
-­ Nu/nu athymic nude • Upregulation of PDGF and VEGF • Appearance of terminal hairs [19]
mice • Downregulation of TGF-­β1 • Increase in the number of hair follicles compared to control
DPC miR-­218-­5p C57BL/6 mice • Upregulation of β-­c atenin • Increase in hair growth [20]
• Downregulation of SFRP2 • Increase in the protein level of β-­c atenin
-­ C57BL/6 mice -­ • Accelerate the onset of the anagen phase, delayed the catagen phase [7]
• Increase in protein levels of β-­c atenin and Shh
-­ C57BL/6 mice -­ • Prolonged anagen phase [13]
a
HaCaT cells -­ C57BL/6 mice -­ • Increase in hair growth [16]
• Increase in protein levels of β-­c atenin and Ki67 in CD34 + cells
hAFSC -­ SD rats -­ • Increase in epidermal layer thickness [21]
• Increase in HF count
MDSC -­ AA-­affected C3H/ • Upregulation of FoxP3 and arginase 1 • Partial hair regrowth [22]
HeJ mice • Downregulation of T cell • Increase in Treg proliferation
hyperactivity • Mitigated cytolytic activity
• Decrease in T helper proliferation
MSCb -­ C57BL/6J mice -­ • Increase in hair density [23]
• Fast onset of hair regrowth
• Increase in protein levels of β-­c atenin, K15, CD34, ALP, and PCNA
Bovine colostrum -­ C57BL/6 mice -­ • Darker skin pigmentation [18]
• Increase in hair coverage
• Transition to the anagen phase
• Increase in the number of Ki67+ cells in hair matrix
• Increase in the protein level of β-­c atenin and Wnt3a
Ex vivo results
ADSC -­ Mice HF -­ • Increase in hair length [11]
• Increase in the number of Ki67+ cells in hair matrix
DPC -­ Human HF -­ • Hair shaft elongation [13]
• Increase in Ki67 positive cells around the dermal papilla
GUPTA et al.

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GUPTA et al. 2429

sheath cell; PCNA, proliferating cell nuclear antigen; PDGF, platelet-­derived growth factor; PL, platelet lysis; PRP, platelet-­rich plasma; SFRP, secreted frizzled-­related protein; Shh, sonic hedgehog; TGF-­β1,
administered 2 or 5 mL of undiluted solutions or up to 8 mL of diluted

ERK, extracellular signal-­regulated protein kinase; hAFSC, human amniotic fluid stem cell; HF, hair follicle; HFSC, hair follicle stem cell; HHORSC, human hair outer root sheath cell; K15, keratin 15; Ki67,
Abbreviations: AA, alopecia areata; ADSC, adipose-­derived stem cell; ALP, alkaline phosphatase; AXIN2, axis inhibition protein 2; CCND1, cyclin D1; DHT, dihydrotestosterone; DPC, dermal papilla cell;
solutions (1:2–­1:5) at alopecic scalp regions. 26 During follow-­up, ad-

antigen KI-­67; LEF1, lymphoid enhancer-­binding factor 1; MDSC, myeloid-­derived suppressor cell; miR, microRNA; MMP-­3, matrix metalloproteinase 3; MSC, mesenchymal stem cell; ORSC, outer root
Ref.

[14]
verse reactions including fever, myalgias, chills, fatigue, or scalp cel-
lulitis were not reported. 26
A recent study performed safety evaluation of exosomes using
in vitro and in vivo models.28 Exosomes were isolated from human-­
induced pluripotent stem cells. Tissue-­specific localization was iden-
tified in the liver, kidneys, brain, and lungs without significant adverse
reactions. Specifically, evidence of hemolysis, DNA damage, and cyto-
lytic effects were not observed; there were no abnormal histological
• Increase in the protein levels of CCND1 and LEF1

findings, along with normal hemocyte, liver and kidney parameters, al-
beit with elevations in immunoglobulins and circulating CD8+ T cells.28
Similar results were also reported in another in vivo study of exosomes
isolated from mesenchymal stromal cells.29 However, differences in
experimental design hamper the clinical translation of these findings,
and there remains an undetermined risk of tumor development and
Observed phenotypic effects

metastasis depending on the source and content of exosomes.30

Further studies are clearly warranted to fully define the molecular and
• Hair shaft elongation

functional characteristics of exosomes from different sources.

transforming growth factor beta 1; Treg, regulatory T cell; VEGF, vascular endothelial growth factor; WIF, WNT inhibitory factor.

3.4 | Regulatory concerns

The U.S. FDA has issued alerts against the use of exosome prod-
ucts.31,32 Exosomes are regulated as a drug and as a biologic, none
signaling pathway (BCL2, CCND1,

of the marketed products are currently approved by the FDA.31,32

• Upregulation of Wnt/β-­c atenin

Several technical challenges exist that hinder the clinical use of

• Downregulation of SFRP2
Observed genotypic effects

exosomes.5,33 Owing to its molecular heterogeneity, no consensus

has been established to date on methods for the isolation and char-
acterization of exosomes, which limits the reproducibility across
CTNNB1, LEF1)

studies. To address this issue, a 2018 guideline was introduced by

the International Society for EVs on experimental design and spe-
Keratinocytes (HaCaT cells) were treated with fisetin (a plant flavonoid extract).

cial considerations when reporting study results.34 Although sev-

eral isolation methods such as ultracentrifugation and ultrafiltration
are available, there remains a possibility that the functional profile
of exosomes reported previously could be due to other subtypes
of EVs. Furthermore, limited detection methods for exosome con-
tent associated with specific functions, such as hair regrowth (e.g.,
miRNA), pose another challenge to its clinical application.33
Rabbit HF
Target

Although described as a “cell-­free” therapeutic product which,

Exosomes were loaded onto a microneedle patch.

in theory, decreases the risk of tumorigenesis and infections com-

pared to stem cell therapy, cases of severe infections were reported
in 2019 due to substandard manufacturing conditions.35 Adherence
miR-­181a-­5p

to good manufacturing practice (GMP) is paramount for minimizing

risks of contamination in the cell-­culture system, such as microbes
Content

including Mycoplasma, as well as intracellular contents that can trig-

ger the host immune response.36,37
TA B L E 1 (Continued)

3.5 | Future directions

Source

In addition to addressing safety issues concerning the isolation

and quality control of exosomes for industrial production, current
b
a
 |

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2430 GUPTA et al.

literature suggests that further improvements can be made to opti-

[24]
Ref
mize its formulation, regimen, and delivery methods.
As aforementioned, the use of topical formulations may im-

site; no serious adverse

Pricking at the injections
prove patient adherence and satisfaction over intradermal injec-

reactions reported
tions owing to fewer required clinic visits, as well as decreased

Adverse reactions
risks of adverse reactions related to pain at the injection site,
systemic side effects, and infections. In addition, this may satisfy
current regulatory issues.
Incorporating exosome treatment in combination regimens may
further improve the clinical outcome. In a mice model study, topical
5% minoxidil applied daily showed synergistic effects with ADSC-­
2

Exo.10 In another study, 11 AGA patients who received autologous

Mean hair density: 146.6 ± 39.5 hairs/cm

ADSC treatment combined with PRP showed more profound rever-

Mean hair thickness: 61.4 ± 10.7 μm
Final hair measurements (p-­value)

sal of hair loss compared to patients treated with PRP alone (51.6%
vs. 21.5%).38 Exosomes present in PRP may complement the effects
of exosome treatment in hair growth.39 However, two recent stud-
ies using PRP-­ or platelet lysate-­derived exosomes reported no sig-
nificant effects in DPCs (Table 1).12,17 The authors have attributed
the lack of efficacy to the purity of the isolated exosomes; further
(p < 0.001)

(p < 0.001)

studies examining alternative isolation methods affecting the phys-

iochemical and functional properties of platelet-­derived exosomes
maybe warranted.5,17,34
Given the current limitations of topical and systemic treatments
on the long-­term efficacy, safety, and compliance, novel methods for
2
Mean hair density: 121.7 ± 37.2 hairs/cm

targeted drug delivery has been an area of ongoing investigation.38

Mean hair thickness: 52.6 ± 10.4 μm

Administration of ADSC-­conditioned media using a microneedle

roller once per week, which creates microchannels in the scalp that
Baseline hair measurements
TA B L E 2 Summary of clinical evidence on the use of exosomes in hair restoration for AGA.

facilitates drug penetration, resulted in significant increases in hair

density and thickness after 12 weeks.40 Similarly, low-­frequency ul-
trasound devices that enhance skin permeability at specific locations
of the scalp may also improve treatment efficacy; however, the reg-
ulatory status needs to be determined. In a study of 30 AA patients,
applications of methylprednisolone or cyclosporine with ultrasound
resulted in marked hair regrowth after 3 months.41 It remains to be
seen if clinically significant delivery of exosomes to the dermis and
subcutis could occur with the use of low-­frequency ultrasound de-
Patients (n)

Abbreviations: ADSC, adipose-­derived stem cell; QW, once weekly.

vices. This may change the cosmetic designation of the therapy.

In addition, delivery systems that enhance the pharmacokinet-
39

ics of exosomes may further improve the utility of topical formula-

tions. Application of a microneedle patch loaded with MSC-­E xo led
12 weeks
Duration

to improved hair coverage compared to the subcutaneous injection

method. 23 Similar findings were also reported using ADSC-­E xo.11
This higher rate of regrowth could be attributed to the improved drug
particles/vial) with

penetration, duration as well as rate of release; the addition of chi-

microneedle roller

tosan lactate may also decrease the risk of bacterial infections.11,23

Scalp application

As the large-­scale production of exosomes is currently limited

(>6 × 1010

due to its low yield in cell culture (<1 μg/mL); strategies that enhance
Regimen

QW

exosome production as reported previously, such as the addition of

plant extracts or phototherapy, as well as protruding cells using serial
porous membranes (i.e., engineered nanovesicles [eNVs]), warrants
further validation.5,8,16,42 In a study applying low-­level laser irradia-
Source

ADSC

tion (LLLI), endothelial exosome production increased by 1.64-­fold

following LLLI treatment through modulations of the Wnt signaling
 |

14732165, 2023, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.15869 by CAPES, Wiley Online Library on [06/05/2024]. 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
GUPTA et al. 2431

F I G U R E 2 microRNA (miRNA) mediated effects through the transfer of dermal papilla cell-­derived exosomes (DPC-­E xo). Exosomes are
secreted following the transport and fusion of multivesicular bodies to the cell membrane. Previous studies have identified two subsets
of DPC-­E xo containing miRNA with modulatory effects on hair growth.14,20 CD9+ CD81+ DPC-­E xo containing miR-­218-­5p demonstrated
favorable effects in a mice model study. 20 While CD9+ DPC-­E xo containing miR-­181a-­5p demonstrated favorable effects in hair follicle stem
cells and in organ culture of rabbit whisker follicles.14 EV, extracellular vesicle; MVB: multivesicular body; SFRP2, secreted frizzled-­related
protein 2; WIF1, WNT inhibitory factor 1.

pathway.43 Another study demonstrated a 250-­fold increase in C O N FL I C T O F I N T E R E S T S TAT E M E N T

production yield for eNVs compared with the traditional exosome AKG, TW, and JAR have no competing interests to declare.
production method; however, although eNVs and exosomes share
similar molecular characteristics, eNVs in comparison are packaged DATA AVA I L A B I L I T Y S TAT E M E N T
with non-­selective cargos.44 Data sharing is not applicable to this article as no new data were cre-
Lastly, exosomes derived from alternative sources, such as bo- ated or analyzed in this study.
vine colostrum or plants, may be considered to increase produc-
tion yield while adhering to GMP.18,45 Bovine colostrum-­derived E T H I C S S TAT E M E N T
exosomes were shown to enhance DPC proliferation in vitro, and Authors declare human ethics approval was not needed for this
18
improve hair coverage in vivo (Table 1). Similarly, exosome-­like study.
nanovesicles derived from Ashwagandha seeds were also shown to
enhance DPC proliferation in vitro.45 This may allow for a clearer ORCID
path to commercialization. Aditya K. Gupta https://orcid.org/0000-0002-8664-7723
In summary, there has been exciting advances in the field exo- Tong Wang https://orcid.org/0000-0001-9359-9750
some research over the past decade, despite significant roadblocks Jeffrey A. Rapaport https://orcid.org/0000-0003-4454-5400
in its clinical translation. There are important safety concerns yet to
be addressed. For alopecia patients, off-­label exosome treatment has
REFERENCES
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1. Blume-­Peytavi U, Blumeyer A, Tosti A, et al. S1 guideline
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