Discussion
hair loss, half-scalp, trichoscopy
REGRESSION, HAIR LOSS, LENS, STILL
In this study, we aimed to identify whether intradermal administration of ADSC-CM could stimulate hair regeneration in AGA. All 37 patients that enrolled in this study were men (100%), as AGA is more prevalent in males [Treatment of AGA is quite challenging. Available treatment modalities, while abundant, fail to provide a lasting effect on hair growth [Autologous platelet-rich plasma (A-PRP) and adult SCs such as adipose-derived mesenchymal stem cells (AD-MSCs) and human follicle stem cells (HFSCs) are proposed as minimally invasive alternative treatments for AGA. The antiapoptotic effects of A-PRP have been suggested as one of the primary elements encouraging hair growth by extending the survival of dermal papilla cells (DPCs) throughout the hair cycle, stimulating HFSC differentiation, and lengthening the anagen phase. Additionally, it enhanced the perifollicular vascular plexus by raising levels of angiogenic factors [Recent studies have shown that A-PRP as an AGA treatment is clinically beneficial. In a recent study by Gentile et al. the improvement in hair density for A-PRP was 28 ± 2% hairs/cmFew clinical trials have investigated the effects of ADSC-based therapies on the hair cycle in humans. An observational study in 27 females with AGA who were treated with single ADSC-CM intradermal injection resulted in elevated hair density and thickness [We believe that objective evaluation of hair growth is vital to determine the efficacy of our treatment regimen. Hence, we utilized a non-invasive video-trichoscopy device that is able to measure various hair parameters in real time. To our knowledge, we are the only study that included parameters such as VR, TR, MT, and TFU in our data. We observed a significant improvement not only microscopically, as shown in Fig. Microscopic changes observed using trichoscopy at baseline and 6 weeks after ADSC-CM and minoxidil applicationMacroscopic changes were taken using FotofinderOur results demonstrated that concentrated ADSC-CM successfully promoted the increase of HC, HD, TR, MT, and TFU as well as decreased the number of VR compared to baseline. Although patients in the non-concentrated ADSC-CM group also generated similar positive outcomes in hair parameters, we saw a decline in TFU on both the placebo and treatment sides of the scalp. We suspect that this is due to the use of topical minoxidil, which is known for causing initial hair loss after treatment is initiated. The injection of non-concentrated ADSC-CM on the treatment side may have minimized the hair loss, which would account for the greater reduction on the placebo side.Much to our surprise, we found that the majority of hair growth parameters also improved on the placebo side, and there was no statistically significant difference between the groups. Analysis using another statistical method, mixed model linear regression, also showed similar insignificant difference between the groups (Additional file Second, we hypothesize that ADSC-CM might have diffused to the placebo-treated side of the scalp. This could explain why in both sections of the concentrated ADSC-CM group, all parameters increased simultaneously, with very identical results. It is possible that larger concentrations of ADSC-CM enabled a more optimal spread of growth factors, causing the placebo-treated side of concentrated ADSC-CM to have a higher mean in all hair parameters than the non-concentrated ADSC-CM group. Dissemination of growth factors in ADSC-CM through local circulation exert a paracrine effect on the surrounding tissues and cells [To date, our study is one of the first clinical trials to evaluate the efficacy of ADSC-CM combined with minoxidil in AGA. The rationale behind our decision to incorporate 5% topical minoxidil with ADSC-CM in our treatment regimen stems from the fact that 5% topical minoxidil is widely recognized as the first-line standard therapy for AGA. As the safety and efficacy of ADSC-CM use for AGA is currently limited, given the preliminary nature of our pilot study conducted in Indonesia, we found it essential to retain minoxidil as the standard therapy. Still, we believe that ADSC-CM possesses the potential as adjuvant therapy. It is also the first to apply two different concentrations of ADSC-CM, as we believed the culture medium used during production might have diluted the growth factors. Yet, we could not find any statistically significant difference between the use of concentrated and non-concentrated ADSC-CM. Disruption in the expression of growth factors might be a cause, which affects the hair cycle differently depending on age and sex [We believe that outcomes of ADSC-based treatments for AGA vary depending on formulation type, presence of other treatments, and mode of administration. Pre-existing studies which applied different formulations, treatment duration, and study methods have generated variable results [There are certain limitations to our research. First, since the study duration was 6 weeks long, maximum hair growth could not be adequately measured and documented. Even though the ADSC-CM used in our study did not cause any substantial side effects, the short duration of the study may not be able to assure its long-term safety. Furthermore, our results may not be generalizable as our sample size was relatively small. Lastly, the half-scalp comparison study design and the use of minoxidil as standard therapy might have obscured the therapeutic potential of ADSC-CM.Despite these shortcomings, our research still possesses several strengths. This is the first randomized, double-blind clinical trial in Indonesia to assess the potential of ADSC-CM combined with minoxidil for hair regrowth in AGA. Hair regrowth was also measured objectively using trichoscan, which produced more reliable quantitative assessments compared to a photograph-based analysis by an investigator or self-assessments by study participants, both of which have been employed in earlier studies. All patients’ photographic views were taken on the same fixed area of the scalp, including the same light and distance from the lens. All evaluations each week are performed by the same person. As this research was conducted during the COVID-19 pandemic, researchers strongly implemented strict safety and health measures.