Journal of Dermatological Treatment

ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: https://www.tandfonline.com/loi/ijdt20

Objective analysis of volume restoration in

atrophic acne scars and skin pores: a split study
using human stem cell-conditioned media

Chan Seong Park, Ji-Hye Park, Cho Rok Kim & Jong Hee Lee

To cite this article: Chan Seong Park, Ji-Hye Park, Cho Rok Kim & Jong Hee Lee (2019):
Objective analysis of volume restoration in atrophic acne scars and skin pores: a split study
using human stem cell-conditioned media, Journal of Dermatological Treatment, DOI:
10.1080/09546634.2019.1628915

To link to this article: https://doi.org/10.1080/09546634.2019.1628915

Accepted author version posted online: 07

Jun 2019.
Published online: 05 Jul 2019.

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JOURNAL OF DERMATOLOGICAL TREATMENT
https://doi.org/10.1080/09546634.2019.1628915

ARTICLE

Objective analysis of volume restoration in atrophic acne scars and skin pores: a
split study using human stem cell-conditioned media
Chan Seong Parka , Ji-Hye Parka , Cho Rok Kimb and Jong Hee Leea,c
a
Samsung Medical Center, Department of Dermatology, School of Medicine, Sungkyunkwan University, Seoul, Korea; bDepartment of
Dermatology, Kye Dermatology Clinic, Seoul, Korea; cDepartment of Medical Device Management & Research, Samsung Advanced Institute for
Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea

ABSTRACT ARTICLE HISTORY

Background: It is anticipated that the combined treatments of ablative laser and human stem cell-condi- Received 4 February 2019
tioned media produce the synergistic effects. Accepted 31 May 2019
Objectives: To investigated the effects of human stem cell-conditioned media (HSCM) as a post-proced-
KEYWORDS
ural agent after fractional CO2 laser procedure in patients with atrophic acne scars and skin pores.
Antera 3DV CS; atrophic
R

Method: Both cheeks of 15 subjects were treated with a fractional CO2 laser. HSCM was randomly acne scar; fractional CO2
applied to one of the resurfacing sites (T) and normal saline was applied to the other site as a control laser; human stem
(C). During the next six days, a solution containing 80% HSCM and hyaluronic acid (HA) was applied on cell media
the treated side (T) and HA alone was applied to the control side (C). Scar volume and erythema were
objectively evaluated using an Antera 3DV CS.
R

Result: After two months, the scar volume was reduced by 23.5% (T) versus 15.0% (C) (p ¼ .143) and the
volume of the skin pores was reduced by 37.6% (T) versus 15.9% (C) (p ¼ .006), while the erythema was
increased by 2.8% (T) versus 3.1% (C) (p ¼ .934). Atrophic scar and the skin pores in the HSCM-applied
area improved by at least 15.0% after a single treatment session, suggesting better results compared
with the control side.
Conclusion: HSCM may augment the regenerative effects of fractional CO2 laser.

Introduction skin regeneration (8–11). However, due to its hydrophilicity, it

Acne is a common skin disease, affecting 80% of adolescents and
young adults and 5% of older adults (1,2). In 95% of the cases,
acne involves exposed areas, such as the face and the upper
body. Further, permanent scarring including chronic sequelae of
inflammatory acne, affects nearly 95% of patients with acne,
which can lead to serious psychological problems (1,3–5). Acne
scars have been classified into three types: atrophic, hypertrophic,
and keloidal. The atrophic acne scars have been the most com-
mon and they have frequently caused psychosocial problems
because they occur mostly on the face and the cheek areas (3,6).
Atrophic acne scars have been treated with a variety of modal-
ities, including tissue augmentation, chemical peels, surgical treat-
ment, dermabrasion, and ablative and non-ablative laser
resurfacing (6). Treatment with fractional CO2 (carbon dioxide)
lasers has been widely used for acne scars and reported to be
effective in up to 26% to 75% of all cases after a single treatment
session. Previous studies have used ECCA (Echelle d’Evaluation
clinique des Cicatrices d’acne) scores or a 4-point scale to evalu-
ate scars, without objectively evaluating scar volume improve-
ment (7).
Recently, the use of human stem cell-conditioned media
(HSCM) has increased in popularity in cosmetology and medicine,
because of its regenerative effects. The HSCM contains an abun-
dance of growth factors, extracellular matrix involved in skin elas-
ticity and scar regeneration, antioxidants, and cytokines
preventing cellular apoptosis, which promotes wound healing and
cannot be absorbed into the skin deeply even when applied daily.
However, the combination of HSCM and ablative laser therapy
has been found to produce synergistic effects.
In this study, we have sought to objectively analyze and quan-
tify the improvement of atrophic acne scars associated with skin
pores in patients treated with fractional CO2 laser and HSCM. A
split-face study has been performed to investigate the clinical
benefits of HSCM, which is known to increase the treatment
responses and reduce possible side effects, such as erythema after
fractional CO2 laser treatment.
Materials and methods
Subjects
This study includes healthy subjects aged 19 to 65 years and diag-
nosed with atrophic acne scars. Patients with preexisting skin con-
ditions, with skin infections, retinoids intakes, those with
photosensitive dermatoses and severe systemic disease, frequently
smoking tobacco, with allergies to topical anesthetic cream, and
those who were pregnant, or lactating have all been excluded.
This study has been approved by the Institutional Review Board
(IRB) of Samsung Medical Center, Sungkyunkwan University
School of Medicine (IRB file number: SMC 2017–04-100). Written
informed consent has been obtained from all study subjects.

CONTACT Jong Hee Lee bell711@hanmail.net Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81
Irwon-ro, Gangnam-gu, Seoul 06351, Korea
ß 2019 Taylor & Francis Group, LLC
2 C. S. PARK ET AL.

Treatment protocol Statistical analyses

All subjects have undergone single treatment session for both The methods of analysis included independent sample t-tests and
cheeks using fractional eCO2 laser (LutronicV, Korea). The lido- paired t-tests. Statistical significance has been defined by p-values
R

caine 2.5% and prilocaine 2.5% cream (EmlaV, AstraZeneca, South equal to or < .05. All statistical analyses have been performed
R

with SPSS statistical analysis software version 21.0 (SPSSV, IBM).

R
Korea) with one-hour occlusion was used for local anesthesia prior
to treatment. Atrophic scar sites were initially treated with an
energy of 20–30 mJ at a density of 400 per 120 mm spot under Results
static mode. Then, the entire cheeks were treated with an energy
of 20 mJ at a density of 200 per 400 mm spot under dynamic The study enrolled 15 participants. All subjects have completed
mode. Subsequently, the face was divided into left and right sides the study and all follow-up visits and the data have been col-
and then randomly assigned for topical application. Following lected for analysis. Of the 15 subjects in total, 12 (80%) were male
randomization, each patient was treated with 100% human adi- and three (20%) were female. The mean age of patients
pose-derived stem cells-conditioned media (SCM2V, Anterogen,
R was 32.0 ± 8.5 years.
South Korea) to one side of their face and normal saline to the
other side. For the next six consecutive days, a solution contain- Volume of atrophic acne scar
ing 80% HSCM with HA (TheraStemV-Derma, Anterogen, South
R

The scar volume was reduced by 28.5% from baseline until week
Korea) was applied to the 100% HSCM-treated side, twice a day.
two in the side treated with HSCM (p ¼ .003) compared with
On the opposite side, HA alone was applied twice daily as a con-
20.3% (p < .001) in the control side. The scar volume was reduced
trol (Figure 1).
17.0% in the HSCM-treated side (p ¼ .006) compared with 7.2%
(p ¼ .038) in the control, by the first month. Finally, it was reduced
Evaluations 23.5% in the HSCM-treated side (p ¼ .001) compared with 15.0%
(p < .001) in the control, by the second month. No statistically sig-
In order to assess the treatment response, we objectively meas-
nificant differences have been detected in the volume of atrophic
ured the volume and erythema of the scar using an Antera 3DV
R

acne scars between the groups at two weeks, one month, and
CS (Miravex, Dublin, Ireland) at baseline, the week 2, and at two months (p ¼ .433, .251, and .143, respectively) (Figure 3).
months 1 and 2 after treatment. The Antera 3DV CS is a novel
R

instrument for objective analysis of 3D images and measurement

of data, such as volume and erythema. Volume of skin pores
Antera 3DV CS accurately displays depressed and erythematous
R

By week 2, the skin pore reduction from baseline was 27.7% on

areas. Furthermore, if one of the areas is used as a reference, this
device generates the image of the same area during the treat-
ment. The volume of the selected area and the degree of ery-
thema are displayed, as well. Antera 3DV CS also automatically
R
displays the graph of the variables, for intuitive assessment of the
results (Figure 2). Each atrophic scar volume was measured indi-
vidually; however, in case of skin pores, the cheeks were analyzed
as a whole.
the HSCM-treated side (p ¼ .088) compared with 11.9% (p ¼ .117)
on the control side. By the first month, it was 26.3% for the
HSCM-treated side (p ¼ .042) compared with 16.3% (p ¼ .335) on
the control side, and by the second month, the skin pores were
reduced by 37.6% on the HSCM-treated side (p ¼ .015) compared
with 15.9% (p ¼ .004) on the control. No statistically significant dif-
ferences have been detected in the volume of skin pores between
the groups at two weeks and one month (p ¼ .254 and .578,

Figure 1. Flowchart outlining the study protocol.


Figure 2. Results in the volume of atrophic acne scar in one patient measured with Antera 3DV CS (baseline, 2 weeks, 1 month, and 2 months after the laser treat-
ment. Bar graphs show the changes in scar volume at each visit).
Figure 3. Average atrophic acne scar volume data measured with Antera 3DV CS
R R
in both groups.
Figure 4. Average skin pore volume data measured with Antera 3DV CS in
R
both groups.
respectively); however, statistically significant differences have
been detected at two months (p ¼ .006) (Figure 4).
Erythema
By week 2, the erythema aggravation from the baseline was 6.2%
on the HSCM-treated side (p ¼ .008) compared with 4.8%
(p ¼ .046) on the control side. By the first month, it was 2.2% on
the HSCM-treated side (p ¼ .388) compared with 2.6% (p ¼ .540)
on the control side. By the second month, it was 2.8% on the
HSCM-treated side (p ¼ .419) compared with 3.1% (p ¼ .365) on
the control. No statistically significant differences have been
detected in erythema between the groups at two weeks, one
month, and two months (p ¼ .628, .904, and .934, respectively)
(Figure 5).
JOURNAL OF DERMATOLOGICAL TREATMENT 3
R
Figure 5. Average erythema data measured with Antera 3DV CS in both groups.
Discussion
Various treatment modalities have been investigated for atrophic
acne scars, among which fractional CO2 laser is one of the most
common procedure (6). However, no objective analysis has been
used for the assessment of acne scars independent of the evalua-
tors in patients treated with fractional CO2 laser.
A previous study conducted by Cho et al. (12) has evaluated
the efficacy and safety of fractional CO2 laser treatment for atro-
phic acne scars in Korean patients. After a single treatment ses-
sion, the treatment responses have been as follows:  25% (mild),
26–50% (moderate), 51–75% (marked), and >75% (excellent). A
single patient (5%) showed excellent outcome, nine (45%)
revealed marked results, seven (35%) had moderate improve-
ments, and three (15%) showed minimal to no improvement after
a three-month follow-up. Another study by Zhang et al. (13) has
compared the efficacy and safety of fractional microplasma radio
frequency with those of fractional CO2 laser for the treatment of
atrophic acne scars. They have used ECCA scores comprising the
sum of six specific types of scars (ranging from 0 to 4) and their
numerical values as a weighting factor (ranging from 15 to 50).
The mean ECCA score dropped from 48.8 to 19.9 (59.2% improve-
ment); however, with this semi-quantitative scale, the actual scar
volume reduction cannot be measured objectively (14). High-reso-
lution ultrasound imaging has also been used to demonstrate the
efficacy of fractional CO2 laser treatment for acne scars in a previ-
ous study (15). Following a single treatment session with frac-
tional CO2 laser, the mean dermal thickness increased by 25%.
This study has been a prospective observational study involving
24 consecutive patients. The follow-up period varied from 41.5 to
91 days after the treatment.
To the best of our knowledge, this is the first study attempting
to quantify atrophic scars and skin pore improvement in patients
4 C. S. PARK ET AL.
with acne treated with fractional CO2 lasers, objectively. This
study has demonstrated an improvement in the volume of atro-
phic acne scars by 15.0 to 23.5% and that of skin pores by
15–37%, following a single session of fractional CO2 laser treat-
ment. Based on this finding, at least four to five treatment ses-
sions are theoretically required to resolve the atrophic scars and
skin pores.
In order to evaluate the clinical efficacy of HSCM after laser
treatment, the laser-treated sides have been divided into two cat-
egories: one side treated with HSCM, and a control exposed to
normal saline and HA. No considerable differences have been
detected in the improvement of atrophic scar volumes between
the HSCM-treated and the control sides. However, a statistically
significant difference has been found in skin pore volume.
Patients with atrophic acne scars also have widened skin pores,
especially on the cheek area, which are also of concern to
patients and dermatologists.
Topical agents containing HA alone are also very popular as
an adjuvant or for post-procedural care (16). Recent studies have
focused on the effects of HA derivatives, including adipose-
derived stem cells combined with HA (8,17). Multi-potent adipose-
derived stem cells promote tissue regeneration and can be easily
obtained from abundant fat tissues. However, they are easily
degradable, suggesting the need for modification or integration
into a scaffold, such as HA, to prevent rapid clearance (8). Herein,
we have shown that application of HSCM combined with HA is
more effective in improving skin pores compared with HA alone,
suggesting that HSCM combined with HA rather than HA alone,
has been more powerful in regenerating tissue, consistent with a
previous study analyzing cartilage defects (18).
Persistent erythema is the most common and challenging issue
in fractional ablative laser treatment (19). Usually, repeated treat-
ments are necessary for atrophic scar treatment using fractional
ablative lasers. Therefore, persistent erythema has been a major
hindrance to further treatment. Most post-procedural topical
agents have focused on minimizing the period of erythema and
preventing post-inflammatory hyperpigmentation (20–23). Very
frequently, intense erythema results in post-inflammatory hyper-
pigmentation (24). Therefore, in this study, we have attempted to
evaluate the effects of HSCM-containing agents on the reduction
of erythema. HSCM did not show any significant improvement in
reducing erythema following fractional CO2 laser compared with
HA application. More importantly, following the application of
HSCM or HA, a well-known and effective post-procedural agent,
erythema persisted in the second month after laser treatment,
albeit with reduced intensity. Thus, repeated treatment using frac-
tional ablative laser treatment is recommended at least two
months after the previous session to avoid or prevent persist-
ent erythema.
Because of their hydrophilicity and high molecular weight,
HSCM and HA barely penetrate the skin through the normal epi-
dermal barrier. Therefore, we applied these agents for six con-
secutive days after the laser procedure to facilitate the entry of
HSCM and HA deeply into the compromised skin barrier. The use
of HSCM and HA for one week may not be sufficient to restore
the skin completely back to normal status. The prolonged applica-
tion of active agents may have changed the results.
Changes in scar volume following ablative laser treatment
have shown three phases: decrease by the second week, increase
by the first month, followed by decrease again at the second
month. This phenomenon can be explained by the three stages
of wound healing: inflammatory, proliferative, and remodeling
phases (25). After fractional CO2 laser treatment, acne scars
undergo repair and recovery. In the second week, edema caused
by acute inflammatory reaction reduced the scar volume. At the
first month, decreased inflammation led to a transient increase in
scar volume and onset of proliferative phase. At the second
month, remodeling may have induced volume improvement. Our
study has been closed after two months of follow-up but consid-
ering that the remodeling process usually lasts more than a year,
the scar volume may have reduced further due to the sustained
treatment effect of fractional CO2 laser.
Conclusion
This study has demonstrated that a session of single fractional
CO2 laser treatment improved the volume of atrophic acne scars
and skin pores by at least 15%. Application of HSCM as a post-
procedural agent has been shown to enhance the regenerative
effects of fractional CO2 laser. The use of HSCM combined with
HA has been more effective for the treatment of dilated skin
pores compared with HA alone. At least four to five treatment
sessions are required to visualize the desirable effects in the atro-
phic scars or skin pores. In addition, repeated fractional CO2 laser
treatment sessions should be performed at least two months
apart to avoid or prevent persistent and prolonged erythema.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This study has been funded by Anterogen Inc. Seoul, Korea.
However, Anterogen had no role in the data collection, data ana-
lysis, data interpretation, manuscript preparation, manuscript
review or approval. This study has also been registered in
National Research Institute of Health (KCT003718).
ORCID
Chan Seong Park http://orcid.org/0000-0001-5809-0561
Ji-Hye Park http://orcid.org/0000-0002-6699-5202
Cho Rok Kim http://orcid.org/0000-0003-4168-4245
Jong Hee Lee http://orcid.org/0000-0001-8536-1179
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