Hair Regeneration in Androgenetic Alopecia using Secretome of Adipose-derived Stem Cells (ADSC) and Minoxidil: A Comparative Study of Three Groups

doi:10.21203/rs.3.rs-4205976/v1

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Research Article

Hair Regeneration in Androgenetic Alopecia using Secretome of Adipose-derived Stem Cells (ADSC) and Minoxidil: A Comparative Study of Three Groups

https://doi.org/10.21203/rs.3.rs-4205976/v1

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Introduction: Androgenetic alopecia (AGA) is one of the most common cause of hair loss disorder, characterized by the shortening duration of anagen phase, increased telogen phase, and miniaturization of hair follicles, eventually leading to their regression. This disorder tends to progress into partial or even complete baldness.Several therapeutic options are now available for AGA, including conventional medications such as finasteride, dutasteride, and minoxidil. However, side effects of these medications are also commonly reported. The use of adipose derived stem cells (ADSCs) and their secreted bioactive molecules, “secretome” has gained attention which could produce many effects for hair growth promotion and has been proven in clinical trials. However, there is still insufficient evidence regarding the comparison of effectiveness of secretome with treatments like minoxidil.

Objective: This study aims to compare the effectiveness and safety of secretome from ADSCs with minoxidil in AGA cases, to provide future reference in the application of cell-based therapy in AGA cases.

Method: 60 subjects were divided into three treatment groups (minoxidil only, secretome only, and combination of both) and were given intervention on week 0, 4, and 8. All subjects were evaluated by physical examination, photography, trichoscopy, and trichoscan until week 12.

Results: All groups showed a statistically significant improvement (p <0.05) on hair growth parameters from week 4, with the best improvement observed on week 12. There were a significant difference between groups on some of the delta hair growth parameters (p <0.05), observed between secretome and combination groups. The combination group had the best improvement substantially on hair growth parameters. Side effects are minimum and only reported by the subjects in minoxidil group.

Conclusion: All of the interventions give a significant improvement on hair growth with the best improvement observed after 12 weeks. However, the best improvement substantially were observed in combination group.

Adipose-tissue derived stem cells conditioned media

androgenetic alopecia

hair regrowth

minoxidil

secretome

stem cells

Androgenetic alopecia (AGA) is a hair loss disorder characterized with the shortening duration of anagen phase, increased telogen phase, and miniaturization of hair follicles, eventually leading to their regression. This hereditary and androgen-dependent disorder tends to progress into partial or even complete baldness.¹ Based on the research conducted in dr. Cipto Mangunkusumo hospital in 2017–2019, AGA is found to be the second most common cause of hair loss in Indonesia.² Several therapeutic options are now available for AGA, including conventional medications such as finasteride, dutasteride, and minoxidil. However, side effects of these medications are also commonly reported.³ Finasteride is an oral medication that inhibits action of dihydrotestosterone (DHT). While it can be effective in slowing hair loss and promoting hair regrowth, some individuals may report side effects including impotence, erectile dysfunction, decreased libido, and ejaculation disorders. Another medication namely minoxidil, a topical solution that can be applied to the scalp, is also associated with side effects like itching, skin irritation, scalp dryness and unwanted hair growth. Additionally, there are other treatment options for AGA, such as platelet-rich plasma (PRP) therapy, low-level laser therapy and transplantation of hair procedure.⁴

The usage of mesenchymal stem cells (MSCs) and their secreted bioactive molecules, often referred to as the “secretome” or “conditioned media” has gained attention in regenerative medicine and therapeutic applications. This includes the use of the secretome from mesenchymal stem cells derived from adipose tissue (ADSCs) for various medical purposes, including hair growth stimulation. This secretome plays a role in producing anti-inflammatory effects, anti-apoptotic effects, angiogenesis, and immunomodulatory effects in relation to hair growth promotion and has been proven in 3 different clinical trials.^5,6

Other studies applying constituent extracts from ADSCs topically have also shown positive results on increased hair count and hair diameter with minimal side effects. It is important to acknowledge that the comparison of the effectiveness of secretome products of ADSCs with established treatments like minoxidil is a critical area of research as there has been no sufficient evidence in Indonesia. While both treatments have shown promise in promoting hair growth, conducting well-designed comparative studies is essential for evaluating their relative effectiveness, safety, and potential as alternatives or complementary therapies for hair loss.⁷

The inclusion of stem cell research and the development of stem cell derivatives in Indonesia’s national development priority sector is a forward-thinking approach that has the potential to yield significant benefits for both healthcare and the economy. Some key points to consider regarding the potential advantages include reduced dependence on imports, especially cosmetics, economic growth, and also innovation and research.

Therefore, this present study aims to compare the effectiveness and safety of secretome from ADSCs with minoxidil in AGA cases, to provide future reference or standard in the application of cell-based therapy and its derivatives in AGA cases.

This study was a single-blind clinical trial using an experimental research design on subjects with androgenetic alopecia. Variables tested in this study was the method of "treatment of AGA by administering secretome concentrate alone (S), compared to using minoxidil alone (M) and with a combination of both (C)." The "evaluation” assessed was the clinical improvement of the research subject, which were carried out by assessing hair growth with clinical examination, and supporting examinations using photography, trichoscopy and trichoscan. The preparation of secretome concentrate from ADSCs was done at the Integrated Service Installation (IPT) Stem Cell Medical Technology at Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine, University of Indonesia (RSCM-FKUI). The study was conducted for 5 months, from August to December 2023 at the dermato-venereology outpatient clinic of Dr. Cipto Mangunkusumo Hospital for recruitment, treatment, and evaluation of research subjects.

Calculation for the sample size of this study was done with the help of G*Power version 3.1 software (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany). For differences in mean hair density, data was obtained based on previous research by Tanglertsampan, where the clinically significant difference between groups was 10, and the standard deviation was 18. Therefore, a total sample size of 51 subjects was obtained. Anticipating a dropout rate of 15%, the overall sample size was 60 subjects. Subjects were then divided into 3 groups; 20 subjects received secretome, 20 subjects received minoxidil, and the other 20 subjects received both treatments. Before selecting samples, it must be ensured that all patients have met the inclusion criteria, stated as follows: Male patients aged 18–59 years, clinical presentation of AGA with Hamilton-Norwood Grade III-VI, and willing to be a research subject, sign a consent form, and commit regular follow-up visits.

While the exclusion criteria are as follows: Hair loss other than AGA, including telogen effluvium, alopecia areata, secondary syphilis, trichotillomania, systemic lupus erythematosus hair loss due to chemotherapy, autoimmune conditions, or malignancies, patients taking oral medications or vitamins aimed at increasing hair growth in the last month, patients applying topical medications aimed at increasing hair growth in the last 2 weeks, patients with active bacterial, viral or fungal infections on the scalp, and patients undergoing AGA therapy cosmetic procedures in the form of PRP injections, laser procedures, or micro-needling in the last 3 months.

All research subjects then underwent history taking to identify complaints, medical history, family history, hair loss history and smoking habits. Subsequently, a physical examination of the research subjects was conducted, including vital signs, body weight and hair pull test. Pictures of patients’ heads were then taken from 7 different angles and hair loss degree was graded using Hamilton-Norwood.

Evaluation of hair growth was performed every month starting from week 0, 4, 8, and 12. Patients’ satisfaction towards their hair growth results was assessed in the third month using the 7-point scale method. Clinical assessment of hair growth were examined through physical and supporting examinations including photography, trichoscan and trichoscopy. Subjects were also given a booklet for evaluation of complaints and side effects experienced at home.

Statistical data were analysed using SPSS® version 21 software. On numerical data, normality analysis was carried out using the Kolmogorov-Smirnov test. Numerical data that is distributed normally were shown in the form of mean and standard deviation, while those that are not normally distributed were presented in the median and interquartile range. Comparison of the mean values of hair growth parameters from baseline and week 4, baseline and week 8, and baseline and week 12 were analyzed using the paired T-test. If the data is not normally distributed, the Wilcoxon test is used. Comparison of the mean values of delta of hair growth parameters between the three research groups was analyzed using the One-way ANOVA test. If the data is not distributed normally, an alternative test is used, namely the Kruskal-Wallis test. The significance limit used in this study was an alpha of 5%. If there was a significant difference observed, the Post-Hoc Bonferroni test was used to analyze which group has the significant difference.

This research was done from August 2023 until December 2023. We have obtained 90 subject candidates from the recruitment process. After the selection process through clinical examination, 60 subjects which met the inclusion and exclusion criteria were obtained. The subjects were divided equally into three groups. Each group received minoxidil, secretome, and combination of both respectively.

Subjects’ Sociodemographic and Clinical Characteristics

All subjects in three groups had a mean age of around 30 years old and above. Mean age of the onset of AGA ranged from 26,3–37,05 years old. Their IMT ranges around 26 which is classified as ‘obese’ based on the Asia-Pacific classification of BMI. Their academic status varies from senior high school to doctoral degree, but the majority of each group has a bachelor’s degree. Based on history taking, all subjects in the three groups had experienced alopecia for around 5 years. Most of them also had a familial history of alopecia, mainly paternally inherited. Majority of the subjects did not have complaints on the alopecia condition.

Of the total, three subjects had diabetes, five had hypertension, and four had hyperlipidemia. None of the subjects had a previous history of cardiovascular disease. Majority of the subjects did not have previous therapy of alopecia and did not take any daily medication. 48 (80%) of the subjects were non-smokers, and 12 (20%) of them were smokers. There were no statistically significant differences on sociodemographic characteristics between groups. The Hamilton Norwood Grading of the subjects are varied, with the commonly found grades are III vertex and V. There was no statistically significant difference between groups. There was improvement on the Hamilton Norwood Grading of the subjects in week 12. Subjects’ sociodemographic and clinical characteristics are presented in Table 1.

Table 1

Sociodemographic and Clinical Characteristics
Sociodemographic and Clinical Characteristics	Groups			P
Sociodemographic and Clinical Characteristics	Minoxidil (n = 20)	Secretome (n = 20)	Combination (n = 20)	P
Age (Years), Median (IQR)	31 (11)	34,5 (11)	35,5 (18)	0,430*
BMI (kg/m²), Mean (SD)	26,46 ± 5,34	26,10 ± 2,21	26,59 ± 3,15	0,912
Waist Circumference (cm), Mean (SD)	91,40 ± 14,82	94,00 ± 8,42	94,10 ± 10,25	0,703
Academic Level, n (%)				0,596^†
Low	0 (0)	0 (0)	0 (0)
Moderate	1 (5)	0 (0)	1 (5)
High	19 (95)	20 (100)	19 (95)
Alopecia Age (Years), Mean (SD)	26,3 ± 7,68	28,15 ± 7,49	37,05 ± 9,10	0,538
Alopecia Duration (Years), Median (IQR)	4,5 (5)	5 (5)	5 (7)	0,708
Familial History of Alopecia, n (%)				0,972^†
None	8 (40)	7 (35)	8 (40)
Paternal	9 (45)	9 (45)	10 (50)
Maternal	2 (10)	2 (10)	1 (5)
Others	1 (5)	2 (10)	1 (5)
Current Complaints, n (%)				0,265^†
No symptoms	11 (55)	17 (85)	15 (75)
Cosmetic Concern	1 (5)	1 (5)	1 (5)
Lowered self-esteem	2 (10)	1 (5)	1 (5)
Itch	5 (25)	1 (5)	1 (5)
Others	1 (5)	0 (0)	2 (10)
Previous Therapy of Alopecia, n (%)				0,017^†
None	16 (80)	10 (50)	15 (75)
Topical Minoxidil	0 (0)	5 (25)	0 (0)
Topical Tonic Hair	0 (0)	0 (0)	0 (0)
Oral Finasteride	1 (5)	2 (10)	2 (10)
Oral Supplements	1 (5)	1 (5)	0 (0)
Interventional Therapy	2 (10)	2 (10)	3 (15)
Previous Medical History, n (%) Diabetes Hypertension Hyperlipidemia Cardiovascular Disease	2 (10) 1 (5) 0 (0) 0 (0)	0 (0) 0 (0) 1 (5) 0 (0)	1 (5) 4 (20) 3 (15) 1 (5)	0,349^† 0,059^† 0,153^† 0,362^†
Current Medication, n (%) None Oral Finasteride Systemic Oral Medication Supplements Others	17 (89,5) 0 (0) 2 (10, 5) 0 (0) 0 (0)	19 (95) 0 (0) 1 (5) 0 (0) 0 (0)	14 (70) 0 (0) 6 (30) 0 (0) 0 (0)	0,339^†
Smoking, n (%) No Yes	16 (80) 4 (20)	16 (80) 4 (20)	16 (80) 4 (20)	1,000^†
Hamilton Norwood Grade, n (%)				0,645^†
III III Vertex IV V VI	1 (5) 8 (40) 4 (20) 5 (25) 2 (10)	1 (5) 6 (30) 2 (10) 9 (45) 2 (10)	1 (5) 4 (20) 6 (30) 5 (25) 4 (20)
*Kruskal-Wallis Test, ^†Chi-Square Test

Clinical Photography and Satisfaction Factor of the Subjects

Clinical photography of subjects from each group all showed improvement from all of the seven positions of the photos, as seen from one of the subject from each group in Fig. 1. From the seven point scale satisfaction questionnaires, 50% of the subject strongly agree that there were significant hair growth after treatment, 56,7% strongly agree that the treatment reduced hair loss, 56,7% felt strongly agree that their confidence increases after treatment, and 50% felt strongly agree that they had better physical appearance after receiving treatment. Furthermore, 53,3% of subjects strongly agree that the treatment gave effects and results as expected and 75% of subjects would strongly agree to recommend the treatment.

Hair Growth Parameters

In all groups, there were statistically significant differences found from baseline to week 12 as seen on Table 2. There were increasing numbers of anagen and terminal hair growth parameters, and reduced numbers for telogen and vellus hair parameters. There were also declining numbers of hair count and hair density on Week 4 for all groups, and Week 8 for the M group.

Table 2. Difference in hair growth parameters on week 0 and 12, on three different treatment groups

*Wilcoxon Test

Delta of Hair Growth Parameters

There were no statistically significant differences (p > 0,05) found for the delta of hair growth parameters across all groups on week 4 and week 8, as seen on Table 3. However, the C group showed the most positive results among all groups.

On week 12, there were statistically significant differences found on the delta of anagen hair rate, telogen hair rate, telogen hair count, and telogen hair density. Because of that, we analyzed the data using the Post-Hoc Bonferroni Test. The results showed that between the S group and the combination group, there were significant differences (p < 0,05).

Table 3

Delta of hair growth parameters in three different treatment groups.
Clinical Characteristics	W0-W12			P
Clinical Characteristics	Minoxidil (n = 20)	Secretome (n = 20)	Combination (n = 20)	P
Δ Hair Count, Mean (SD)	32,55 ± 20,69	36,35 ± 27,11	30,98 ± 40,86	0,851
Δ Hair Density, Mean (SD)	36,01 ± 22,91	40,19 ± 30,07	34,93 ± 39,05	0,855
Δ Hair Rate Anagen, Mean (SD)	16,44 ± 5,81	11,51 ± 14,21	20,12 ± 5,66	0,020
Δ Hair Rate Telogen, Mean (SD)	-16,44 ± 5,81	-11,50 ± 14,20	-20,12 ± 5,66	0,020
Δ Hair Count Anagen, Mean (SD)	50,80 ± 15,61	49,50 ± 21,54	54,60 ± 22,94	0,712
Δ Hair Count Telogen, Mean (SD)	-15,65 ± 10,73	-13,20 ± 9,11	-23,05 ± 16,04	0,038
Δ Hair Density Anagen, Mean (SD)	56,47 ± 16,80	54,80 ± 23,85	60,45 ± 25,39	0,715
Δ Hair Density Telogen, Mean (SD)	-17,43 ± 11,66	-14,61 ± 10,08	-25,81 ± 18,32	0,035
Δ Hair Rate Terminal, Mean (SD)	39,51 ± 18,71	33,11 ± 20,59	45,40 ± 14,19	0,107
Δ Hair Rate Vellus, Mean (SD)	-40,00 ± 19,43	-33,11 ± 20,59	-45,41 ± 14,18	0,112
Δ Hair Count Terminal, Mean (SD)	81,60 ± 43,99	76,75 ± 40,75	88,95 ± 18,22	0,468
Δ Hair Count Vellus, Mean (SD)	-46,60 ± 42,08	-40,45 ± 24,85	-57,40 ± 31,53	0,279
Δ Hair Density Terminal, Mean (SD)	93,55 ± 43,77	84,96 ± 28,71	98,46 ± 20,17	0,416
Δ Hair Density Vellus, Mean (SD)	-54,39 ± 40,68	-44,78 ± 27,53	-63,54 ± 34,91	0,242
Δ Mean Thickness, Mean (SD)	0,023 ± 0,009	0,020 ± 0,008	0,026 ± 0,007	0,072
Δ Total Follicular Unit, Mean (SD)	11,75 ± 11,12	12,35 ± 16,08	5,95 ± 25,95	0,496
Δ Average Hair Unit, Mean (SD)	0,22 ± 0,13	0,18 ± 0,11	0,18 ± 0,13	0,525
* Kruskal-Wallis Test

Trichoscopy

There were improvements on white dots from baseline (68,3%) to week 12 (36,7%), hair diameter diversity from baseline (90,0%) to week 12 (33,3%), as seen on the trichoscopy photo on Fig. 2. There were no significant differences between groups. However, the combination group showed the best improvement on white dots from baseline (41,5%) to week 12 (22,7%). Only four subjects had peripillar signs, which disappeared on week 12, as seen on Fig. 3. None of the subjects had yellow dots. All subjects had vellus hairs on baseline, week 4, week 8, and week 12.

Sociodemographic and Clinical Characteristics

In this study, we aimed to discover the effectiveness of each treatment, with minoxidil, secretome, and combination of both. All 60 subjects of this study were men. We discovered that the mean age of the subjects in all groups are 31, 34,5, and 35,5, with the onset age ranging from 27–37. It could be concluded that our subjects are mostly early-onset AGA, which were characterized by the onset of AGA < 30.⁸ A study by Ding et al stated that early-AGA are most likely to be inherited through paternal pattern.⁹ The statement correlates with our findings, that most of the subjects in each group had paternal familial history of AGA.

Previous study by Esra, et al on early-onset AGA found that people with moderate to severe AGA had a greater body mass index, which concludes that dietary habits and lifestyle have roles in early-onset AGA.¹⁰ In our study, we found that the subjects’ BMI across all groups were obese and had mean waist circumference > 90 cm. No statistically significant differences were found between groups.

Most of the subjects did not have any complaints towards the alopecia. Some of them had concerns regarding low self esteem, cosmetic concern, and itch. A systematic review by Frith et al stated that from 10 studies and 6 assessments, three assessments reported AGA men had lower self esteem than normal group, while three assessments reported that self-esteem levels of AGA men is still within the normal range or even higher than the normal group. Overall, there were minimum evidence that AGA men had lower self-esteem.¹¹ Furthermore, study by DeMuro-Mercon et al reported that men with moderate to extensive AGA were unbothered by the condition.¹² This may be due to the limited knowledge of the patients that AGA could be treated and feeling of helplessness towards the therapy of AGA.

A cross sectional study by Salem et al stated that prevalence of AGA is statistically greater among smokers than among non-smokers.¹³ In our study, we found that 80% of the subjects were non-smokers. This may be concluded that smoking was not the only major factor that contributed to AGA.

Our study found that the most common AGA type was III vertex across all groups. This finding was in concordance with an epidemiological study by Salman, et al which also discovered the most common AGA type were III vertex, that were mostly found on subjects with age of 30-39.¹⁴

Hair Growth Parameters and Trichoscopy

Topical minoxidil is known to treat AGA through arteriolar vasodilation, reducing pro-inflammatory cytokines, and increasing vascular endothelial growth factor (VEGF) levels. It is also known that the earliest effects of minoxidil starts at 6–8 weeks and reached maximum effects by 12–16 week.¹⁵ A study by Goren et al reported that less than 40% patients gave positive responses after 16 weeks of application.¹⁶ In our study, minoxidil group showed declining level of hair count and density on week 4 & 8. This may be caused by shortening of the telogen phase by minoxidil. The effects may persist on 8 weeks after initiating the treatment.¹⁷ The hair shedding phenomenon caused by minoxidil were also found on a study by Blume-Pevtavi et al, which were found on 12,5% subjects that were using 5% minoxidil topical foam.¹⁸ However, there was a significant increase of anagen hair rate, anagen hair count, anagen hair density, and terminal hair rate, also significant drops of telogen hair rate, telogen hair count, vellus hair count, and vellus hair density on week 4–12. These findings are in concordance with an experimental study that showed increase of anagen phase in the dermal papilla with minoxidil use.¹⁹

Secretome are known to improve hair growth due to its composition of vascular endothelial growth factors, platelet-derived growth factor, and keratinocyte growth factor.²⁰ A study by Fukuoka et al discovered that all subjects with AGA shown a statistically significant improvement in hair growth compared to baseline, with four treatment sessions of secretome injection over 3–4 month period for best results.²⁰ In our study, we found that there were a statistically significant difference on anagen and telogen hair parameters after one treatment session over 4 weeks, and two treatment sessions over 8 weeks. However, there were declining numbers on hair count and hair density after one treatment session over 4 weeks, which was never reported in previous studies. Although, both hair count and hair density rise back significantly on week 8 and 12. The increase on anagen hair rate and hair density also reported by Narita et al with the intradermal injection of secretome monthly for total 6 months.²¹

Combinations of both minoxidil and secretome are known to increase hair growth parameters. From our previous study, the hair growth parameters increase on week 6 after intervention with concentrated secretome and minoxidil.²² In this study, we found that most of the hair growth parameters had statistically significant differences from baseline to week 4, baseline to week 8, and baseline to week 12, with an increased anagen and terminal hair parameters, and reduced telogen and vellus hair parameters. However, there were declining numbers of hair count and hair density on week 4, and an increase on week 8 and 12. The declining numbers may be due to the hair shedding side effects of minoxidil.

To our knowledge, our study is the first one to include a three-arms study, comparing the effectiveness of minoxidil, secretome, and combination of both. As we already tested the combination of both in the previous study, we need to find the effectivity of each treatment alone. We found that each treatment had a statistically significant difference from baseline on week 4, week 8, and week 12 on the hair growth parameters. This could be concluded that all of the treatments are eligible to give similar significant improvement.

Furthermore, we found that there were no statistically significant differences in the delta of the hair growth parameters on week 4 and 8. There were significant differences in the delta of hair anagen rate, hair telogen rate, telogen hair count, and telogen hair density in week 12, while the significant differences were observed in the secretome and combination group. There were also improvements on trichoscopy with the reduced white dots and hair diameter diversity on week 12. White dots are known as the opening of sweat glands and empty follicular ostium, which is seen in sun-exposed scalp. Hair diameter diversity is defined as > 20% variability in hair diameter which is seen in many early cases.²³

The best improvements overall were observed on the combination group. We hypothesized that the combination of minoxidil and secretome had synergistic effects and complements each other in hair growth. Minoxidil works on increasing VEGF while secretome contains abundance of VEGF. VEGF is known to increase perifollicular angiogenesis, which improves the size of hair shafts and follicles.²⁴ Furthermore, the side effects of hair shedding of minoxidil were not observed in combination group on week 8, which could be hypothesized that the secretome as an adjuvant therapy could help to subside the side effects. The significant difference in secretome and combination group on anagen and telogen hair growth parameters may be due to the telogen shortening effects of minoxidil, which rapidly shifts the telogen phase in 1–2 days, compared to the normal telogen phase of 20 days.²⁵ The effect of phase shift have not yet reported in secretome usage. Therefore, the combination of minoxidil in secretome therapy helps in shifting the telogen phase to anagen phase.

However, minoxidil as the standard treatment has several weaknesses, which are the adverse effects and the high need for patients’ compliance. A review by Suchonwanit et al stated that the most reported side effects of topical minoxidil were intolerance, pruritus, erythema, dermatitis, and headache.²⁵ Topical minoxidil treatment also had challenges in the patients’ compliance, which Shadi et al reported that 86,3% of patients with AGA that received minoxidil discontinued the treatment, despite having no side effects. The discontinuation factors noted were longer duration of use, perceived improvement, and the occurrence of side effects.²⁶ Injection of secretome could be the alternative for patients who did not wish to experience the adverse effects nor had the low compliance, which had minimum side effects reported and lower need of compliance because of only one injection for every four weeks.

Our study’s limitations were the duration of follow up and the numbers of intervention. Further research with a longer follow up period and more sessions of intervention could be done to observe the improvement of AGA over time after the interventions.

All of the interventions (minoxidil, secretome, and combination of both) could improve all of the hair growth parameters in a four week period, with best results in a 12 week period. However, the most substantially significant improvements were observed in the combination group. Further research using longer duration of follow up and more sessions of intervention is required to furthermore compare the differences with each group.

Ethical Approval and Consent to Participate

The research was approved ethically under the title “Regenerasi Rambut pada Alopesia Androgenetik Menggunakan Sediaan Sekretom dari Sel Punca Mesenkimal Asal Jaringan Adiposa (SPM-AD) dan Minoksidil: Sebuah Studi Komparasi Tiga Kelompok”. The Health Research Ethics Committee of Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital (HREC-FMUI/CMH) approved the study with decision number KET-977/UN2.F1/ETIK/PPM.00.02/2023 in July 24, 2023. The Innovation and Intellectual Property Management Unit of Dr. Cipto Mangunkusumo Hospital issued the location permit to conduct the research on August 16, 2023, with decision number YR.02.01/2.6.1/0933/2023. The research was also registered in clinicaltrial.com with decision number NCT06066827. Prior to the study, we provided a thorough explanation about the research protocol and asked the participants to sign a consent form before enrolling in the study.

Consent for Publication

All participants had given consent for images or other clinical information relating to their case to be published in a medical publication. The writers will make substantial efforts to conceal their identities.

Availability of Supporting Data

All of the data acquired or analyzed during this study are included in this article. Other data that support the findings of this study are not openly accessible due to reasons of privacy. Further enquiries regarding the data access can be directed to the corresponding author.

Competing Interests

The authors have no conflicts of interest to declare.

Funding

This study was funded by the Ministry of Research, Technology, and Higher Education through its Kedaireka Matching Fund Grant in the year 2023 with decision number 15/E1/PPK/KS.03.00/2023. The funding party had no role in the design of the study and data collection, data analysis, interpretation of data and in writing process of the manuscript.

Author Contributions

All authors gave their contribution to the study preparation and design. Material preparation, data collection were performed by LL, IBSS, SNY, SPS, EN, FDR, NPH, and BCL. IKL, TK, and ISP contributed on the preparation of tools and materials for the research. Data analysis is performed by LL, FDR, NPH, and BCL. The first draft of the manuscript was written by LL and FDR. All authors gave revisions on previous versions of the manuscript. All authors have read and gave approval to the final manuscript.

Acknowledgements

The authors would like to thank all employees of Stem Cell Medical Technology Integrated Service Unit, PT. Kimia Farma, Tbk, and the dermato-venereology outpatient clinic of Dr. Cipto Mangunkusumo Hospital for their contribution in this research.

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Editorial decision: Major Revision
05 Jun, 2024
Reviewers agreed at journal
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Hair Regeneration in Androgenetic Alopecia using Secretome of Adipose-derived Stem Cells (ADSC) and Minoxidil: A Comparative Study of Three Groups

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