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Review

A Decade of Autologous Micrografting Technology in Hair Restoration: A Review of Clinical Evidence and the Evolving Landscape of Regenerative Treatments

by
Vera Wang
1,*,
Antonella Tosti
2,
Antoniya Ivanova
3,
Marta Huertas
4 and
Colombina Vincenzi
5
1
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91765, USA
2
Dermatology Department, University of Miami, Miami, FL 33416, USA
3
Regenera Activa Worldwide, 08031 Barcelona, Spain
4
Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Barcelona, Spain
5
Private Practice, 40138 Bologna, Italy
*
Author to whom correspondence should be addressed.
Cosmetics 2025, 12(6), 254; https://doi.org/10.3390/cosmetics12060254
Submission received: 4 October 2025 / Revised: 26 October 2025 / Accepted: 3 November 2025 / Published: 11 November 2025
(This article belongs to the Section Cosmetic Dermatology)
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Abstract

Androgenetic alopecia (AGA) is a prevalent, multifactorial hair disorder affecting a substantial portion of both males and females, with significant psychosocial consequences. Over the past decade, regenerative medicine has reshaped AGA treatment, offering biologically driven alternatives to conventional pharmacological and surgical therapies. Among these, Autologous Micrografting Technology (AMT) (Regenera Activa® by Rigenera® Technology, Barcelona, Spain) emerged 10 years ago as a notable innovation leveraging the body’s intrinsic regenerative potential through micrografts derived from a healthy scalp tissue. This review provides a comprehensive overview of the pathophysiology of AGA—including genetic, hormonal, and inflammatory contributors—and evaluates the clinical efficacy, safety, and mechanistic basis of AMT in comparison with other regenerative strategies such as platelet-rich plasma, adipose-derived mesenchymal stem cells, and exosome-based treatments. Clinical studies demonstrate that AMT yields significant short-term improvements in hair density and thickness with favorable safety outcomes. Moreover, advancements in device technology and treatment protocols have enhanced consistency and reproducibility. As multimodal and personalized approaches gain traction in hair restoration, AMT is a minimally invasive point-of-care procedure within the evolving regenerative landscape. Future studies are warranted to optimize treatment algorithms, extend follow-up data, better define patient selection criteria for maximizing outcomes with AMT, and expand the indication of autologous micrografting technology.

1. Introduction

Androgenetic alopecia (AGA) is the most common multifactorial hair disease, presenting clinically with hair thinning and decreased hair density and affecting about 80% of males and 50% of females [1]. Typically, AGA is diagnosed in genetically susceptible men and women in specific patterns, namely male pattern hair loss (MPHL) and female pattern hair loss (FPHL) [2]. MPHL describes recession of the frontal hairline and/or diffuse hair thinning at the vertex, and, eventually, a loss of all but the marginal parietal and occipital hair. FPHL typically presents as a diffuse reduction in hair density that mainly affects the mid and frontal regions of the scalp with preservation of the frontal hairline [3,4]. While AGA does not typically cause serious medical problems, it can have significant psychological and emotional impacts, affecting self-esteem and quality of life. Along with studies suggesting growing prevalence of AGA, there has also been growing awareness of this condition by both healthcare professionals and patients [5].
AGA is a chronic condition and treatment requires frequent medical visits, ‘off-label’ drugs, and outpatient procedures, most of which are not reimbursed by medical insurance [5]. Each case must be treated individually, so patient-doctor collaboration to accurately discuss treatment options and relay patient history, lifestyle habits, and other secondary contributing factors is crucial. This helps not only to optimize treatment, but also to estimate the prognosis of AGA in the patient [6].
Current therapies are mainly topical and oral medications, including minoxidil, finasteride, and dutasteride. Combination therapies are not definitively supported by the literature; however, many patients exhibit significant improvements utilizing more than one therapy and/or procedure. Most commonly, topical and oral drugs are combined and have demonstrated a significantly superior clinical response to single drug therapy [7]. The cost varies depending on location and individual case, however AGA treatment ranges between $100 and $15,000 over 5 years [6].
Over the past decade, regenerative medicine has presented additional options in the field of hair restoration, shifting the focus from traditional pharmacological and surgical interventions to also include alternative procedures in the “point-of-care”. Autologous Micrografting Technology (AMT) emerged more than 10 years ago as another approach, leveraging the body’s own regenerative potential to stimulate hair follicle growth and improve scalp health [8].
The growing interest in regenerative medicine underscores the need for a comprehensive assessment of emerging treatment alternatives, particularly in the management of AGA and other hair loss conditions. Furthermore, as the landscape of hair restoration continues to evolve, understanding the integration of AMT into multimodal treatment approaches will be crucial for optimizing patient outcomes. By documenting the clinical and technological progress, as well as efficacy and safety, of AMT, this review seeks to provide valuable insights for clinicians, researchers, and stakeholders in the field of regenerative medicine and trichology.

1.1. Pathophysiology of Androgenetic Alopecia

Hair follicles (HF) are complex and dynamic mini-organs that can regenerate throughout adult life. Stem cells in the bulge of HFs permit cyclic transition between stages of rapid growth (anagen phase), apoptotic involution (catagen phase) and relative quiescence (telogen phase) [9]. At any given time, 80–90% of the HFs are in the anagen phase whereas only 1–2% and 5–15% are in the catagen and telogen phase, respectively. When this cycle is dysregulated, HFs either become non-functional or dead, leading to a progressive decline in a defined pattern [10].
AGA is a non-scarring multifactorial alopecia caused by the interaction between genetics, hormonal factors, metabolic factors, micronutrients, micro-inflammation, and skull bone prominences that influence scalp blood supply. Systemic and environmental factors such as aging and stress also contribute, all leading to altered crosstalk between numerous cell subpopulations, causing blood vessels regression in the dermal papilla (DP) and hair miniaturization [11,12].
AGA has a genetic basis, supported by a high family prevalence and an increased maternal predisposition. It follows a polygenic pattern, as demonstrated by a genome-wide association study that revealed the involvement of 71 loci, some included in the X chromosome. These involved the AR/EDA2R locus, the PAX1/FOXA2 locus and the HDAC9 locus [13].
Sex hormones, particularly androgens, play a crucial role in the onset and progression of AGA. During puberty, increased androgen levels act on androgen receptors in DP cells, causing enlargement of HFs in hormone-sensitive areas of the scalp [14]. However, in genetically predisposed individuals, this same androgenic stimulation that initially promotes follicle growth turns, with advancing age, into a deleterious process that leads to follicle miniaturization [15].
Testosterone, the main circulating androgenic hormone, is converted into its most active metabolite, dihydrotestosterone (DHT), by the enzyme 5α-reductase. DHT binds with high affinity to the ARs in DP cells, altering intracellular signalling. This binding inhibits the Wnt/β-catenin signalling pathway, which is crucial for the proliferation and differentiation of hair follicle stem cells, thus impairing the normal follicular cycle [16,17]. Heightened androgen sensitivity is most pronounced in the DP cells of balding scalp regions, where increased AR and type II 5α-reductase expression facilitate local DHT production and signaling. This imbalance helps explain the variability in the follicular response to androgens and the selective distribution of hair loss in different areas of the scalp [18].
Microinflammation is another factor in the pathogenesis of AGA. Histological studies have found mild, chronic inflammatory infiltrates—primarily lymphocytes and macrophages—around the upper third of hair follicles in affected scalp regions, often accompanied by perifollicular fibrosis and thickening of the follicular sheath. These are closely linked to the miniaturization of hair follicles characteristic of AGA [19]. This microinflammation is distinct from the more aggressive inflammation seen in scarring alopecia and is thought to be a slow, silent process that may contribute to disease progression and reduced response to treatments like minoxidil [20].
Recent molecular and spatial transcriptomic analyses have revealed changes in the immune microenvironment of AGA scalps, including increased infiltration of specific immune cells (such as CD4+ T cells, mast cells, and γδ T cells) and activation of immune-related pathways, particularly those involving interferon-γ signaling [21]. While microinflammation is involved, it may not be the sole driver of follicular miniaturization [22]. Overall, microinflammation is now considered an integral, though secondary, component of AGA pathogenesis, reinforcing the effects of genetic and hormonal factors and representing a potential target for future therapeutic strategies [23].

1.2. Differential Diagnosis

AGA is a clinical diagnosis, relying heavily on patient perception of hair loss, medical history, and clinical examination to evaluate hair density and capture macroscopic pictures of the patient’s baseline. In AGA, a loss of density in the frontal, parietal and/or vertex areas is expected following a MPHL or FPHL that can be classified in the Norwood–Hamilton scale or the Ludwig scale, respectively [24,25]. Furthermore, the pull test will be negative [19]. Trichoscopy can also help identify characteristic features (Table 1).

2. Approved Treatments

AGA therapy primarily aims to prevent follicular miniaturization and slow hair loss [12]. Currently, the only FDA-approved treatments for AGA are topical Minoxidil and Finasteride or oral dutasteride [7,11].

2.1. Minoxidil

The exact mechanism of action of Minoxidil in promoting hair growth is not fully understood, but several potential pathways have been identified. Minoxidil is a prodrug converted to its active form, minoxidil sulfate, through sulfation by the sulfotransferase SULT1A1. Once activated, it serves as an adenosine triphosphate-sensitive potassium channel opener, leading to the hyperpolarization of cell membranes. Minoxidil also contains a nitric oxide moiety and may act as a nitric oxide agonist, potentially influencing hair growth cycles by transitioning follicles from the telogen phase to the anagen phase [26]. These are both thought to widen blood vessels, increasing the delivery of oxygen, blood, and nutrients to hair follicles [27].
Additionally, minoxidil has been shown to downregulate AR expression and inhibit enzymes involved in androgen metabolism (CYP17A1) while increasing aromatase (CYP19A1) activity, thereby reducing local DHT formation and androgenic signaling in affected follicles [28].
The effectiveness of minoxidil can vary among individuals due to differences in enzyme expression levels. Low sulfotransferase activity has been associated with a lack of response to topical minoxidil treatment [29,30,31]. Despite its widespread use, minoxidil has certain limitations. It is less effective in individuals with extensive areas of hair loss and has shown greater efficacy in younger men who have experienced hair loss for less than five years [32]. Additionally, minoxidil is primarily indicated for central (vertex) hair loss and may not be as effective for other patterns of hair loss [27].

2.2. Finasteride

Finasteride selectively inhibits the type II and III isoforms of the enzyme 5α-reductase, which are responsible for converting testosterone into dihydrotestosterone (DHT) in tissues such as the prostate gland, skin, and hair follicles [33]. By reducing DHT levels, finasteride decreases androgen signaling in these tissues, thereby mitigating hair loss associated with AGA [34].
Clinical studies have demonstrated that finasteride can lower circulating DHT levels by approximately 65–70% with a daily oral dose of 5 mg, and reduce DHT levels in the prostate gland by up to 80–90% with daily doses of 1 or 5 mg [35].
However, finasteride is associated with several potential side effects such as decreased libido, erectile dysfunction, reduced semen volume, and gynecomastia (enlargement of male breast tissue) [36]. While these adverse effects are generally reversible upon discontinuation of the medication, there have been reports of persistent sexual side effects in a subset of patients, a condition referred to as post-finasteride syndrome [37].

2.3. Dutasteride

Dutasteride is an oral medication primarily used to treat benign prostatic hyperplasia, but it has also been employed off-label for AGA. It functions as a 5α-reductase inhibitor, targeting all three isoforms of the enzyme responsible for converting testosterone into DHT. By inhibiting this conversion, dutasteride significantly reduces DHT levels, that play a critical role in the miniaturization of hair follicles [38]. Clinical studies have demonstrated that dutasteride can lower circulating DHT levels by approximately 94.7% over 24 weeks, surpassing the reduction achieved by finasteride [39].
This decrease in DHT contributes to its effectiveness in promoting hair regrowth and slowing hair loss progression in individuals with AGA. However, the use of dutasteride is associated with potential side effects, like those reported for oral finasteride, as they have a similar mechanism of action [40].

3. Regenerative Medicine-Based Treatments

Regenerative medicine-based treatments for AGA, including platelet-rich plasma (PRP), exosomes, adipose tissue-derived mesenchymal stem cells (AT-MSCs), and Regenera Activa®, represent an alternative approach to hair restoration. These biologically driven therapies aim to stimulate hair follicle regeneration and delay or reverse follicular miniaturization by using autologous tissue sources of regenerative cells, growth factors, cytokines, and extracellular vesicles (like exosomes) [41]. The mechanisms of action across these therapies typically involve progression of the hair cycle, enhancement of angiogenesis, immunomodulation, and activation of key pathways such as Wnt/β-catenin signaling throughout paracrine communication [42].
These interventions are performed as point-of-care procedures and rely on the intraoperative preparation of the final product, which is reintroduced into the patient scalp. It is essential that clinicians employ original, certified technologies that meet countries’ regulatory standards. In particular, verification of the official certification mark and consultation with the authorized manufacturer or distributor are strongly recommended prior to device use [43]. This step ensures compliance with medical regulations and maintains the quality and traceability of the components involved for protecting patient safety and clinical outcomes.
Incorporating best practices is critical not only for the consistency of results but also for upholding ethical and regulatory standards in clinical practice. As the popularity of regenerative treatments grows, so too does the responsibility of practitioners to ensure that every aspect of the treatment, from technique to equipment, adheres to validated and approved protocols [44].

3.1. Platelet-Rich-Plasma (PRP)

PRP therapy involves drawing a patient’s blood, processing it to concentrate platelets, and injecting the resultant plasma into the scalp. The plasma contains high concentration of growth factors and cytokines, stimulating the Wnt/β-catenin, ERK, and Akt signaling pathways, promoting hair growth and increasing hair density [45]. PRP also enhances vascularization and angiogenesis around hair follicles, improving blood supply and nutrient delivery, which further supports follicle health and growth. Growth factors released from platelets—such as PDGF, TGF-β, VEGF, and IGF—activate stem cells in the bulge area of hair follicles, and stimulate dormant follicles [46,47].
Previous clinical studies have shown that PRP can improve hair density, thickness, and number of anagen hairs compared to placebo in both men and women with AGA [48,49]. Although PRP shows clinical improvement, the treatment efficacy is influenced by the number of sessions, the age and gender of the patient, and the specific techniques and medical devices used during preparation and administration [50].
PRP therapy is generally considered safe due to its autologous nature, however potential side effects include pain at the injection site, scalp tension, swelling and, in rare cases, infection. Moreover, results only persist with maintenance treatments every 6–12 months after the initial three to four monthly treatments, as discontinuation can lead to a resumption of hair loss [51].

3.2. Adipose Tissue-Derived Mesenchymal Stem Cells (AT-MSCs)

MSCs derived from adipose tissue are another emerging AGA treatment. This technique involves two components: freshly derived primary MSCs from the stromal vascular fraction (SVF)-also known as adipose-derived stromal vascular cells (ADSVCs) or adipose-derived regenerative cells (ADRCs)- and isolated, cultured pure adipose-derived MSCs (AD-MSCs). SVF, obtained by removing fat cells from subcutaneous tissue, contains various cell types, including macrophages, neutrophils, vascular endothelial cells, and ADRCs. The presence of multiple cell types may enhance paracrine actions, synergistically promoting hair regrowth and follicular health. Isolated, cultured pure AD-MSCs offer a more defined stem cell population, activating signaling pathways via secretion of exosomes containing micro-RNAs that inhibit the Transforming Growth Factor-β (TGF-β)/SMAD pathway and activate Wnt/β-catenin signaling [52,53,54]. Overall, AT-MSCs activate epidermal stem cells and dermal papilla cells enhancing an immunomodulatory effect and support the transition from telogen to anagen by influencing the subcutaneous adipocyte layer. The choice between these approaches may depend on the desired balance between cellular heterogeneity and stem cell purity, as well as practical considerations regarding preparation and regulatory requirements.
The combination of ADRCs with adipose tissue for enhanced hair growth in patients with male or female pattern hair loss has demonstrated promising results. One study found a 23% increase in hair count with ADRCs versus a 7.5% increase with non-assisted adipose tissue [48]. Various other studies have also shown an increase in hair density and diameter with ADSC treatment compared to controls.
Although effective, treatment with AT-MSCs is costly and involves invasive procedures for adipose tissue extraction and cell manipulation [55]. Additionally, as the procedure has been on the market for only a few years, further studies are needed to assess its long-term efficacy and safety.

3.3. Exosomes

Exosomes are treatments that deliver isolated extracellular vesicles that play a crucial role in cell communication and have gained attention as a novel treatment for AGA (Figure 1). These vesicles are primarily derived from adipose-derived mesenchymal stem cells, containing bioactive molecules such as proteins, lipids, growth factors, mRNAs, and microRNAs [56]. Exosomes promote hair follicle regeneration by delivering growth factors, stimulating DP cells (DPCs), enhancing angiogenesis and reducing inflammation levels. Additionally, they activate the Wnt/β-catenin pathway and inhibit the TGF-β/SMAD signaling axis, extending the anagen phase of the hair cycle while preventing follicular miniaturization [8].
In addition to naturally derived exosomes, synthetic exosomes have been developed to improve consistency and scalability in treatment. These include polymeric nanoparticles, liposomes and engineered extracellular vesicles, which mimic the biological functions of natural exosomes [57]. Synthetic exosomes can be loaded with specific bioactive molecules and offer advantages like improved stability, consistency, and controlled release compared to naturally sourced exosomes [58]. These engineered vesicles have been primarily tested in preclinical settings, demonstrating efficacy comparable to or exceeding first-line agents such as minoxidil [57,58].
Despite their potential, exosome therapy for AGA has some limitations such as the complexity and costs of the production and purification processes, making the treatment less accessible. Moreover, human data is limited and standardized protocols for their application and dosing are still lacking, leading to variability in clinical outcomes [59].

3.4. Autologous Micrografting Technology

AMT (Rigenera Activa® by Rigenera® Technology) has been adopted in clinical practice for over a decade for the treatment of both male and female patients with AGA (Table 2). The system has undergone continuous refinement across four generations of medical devices, with the latest generation N4SA EVO Smart Microblade Technology introducing significant technical advancements that further optimize the quality of micrograft suspension. These include enhanced mechanical disaggregation through improved torque control, a more homogenous tissue breakdown process, and advanced stability via better temperature regulation [2]. The integration of touch-screen LCD controls and automated calibration processes also reduces human error and intervention, streamlining the clinical workflow. All these innovations minimize mechanical and thermal stress on the harvested tissue, resulting in micrografts with up to 90% cell viability and a 50% increase in the concentration of biological components such as growth factors and EVs like exosomes [20].
The final product is a suspension of 80 µm micrografts derived from small tissue biopsies at the patient’s occipital scalp region which are subsequently injected into AGA-affected areas. These autologous micrografts contain HF-MSCs, DP cells, and other dermal cell populations with regenerative potential, along with their full secretome—including tissue specific growth factors, cytokines, extracellular matrix fragments, and exosomes. These collectively stimulate follicular stem cell proliferation, promote angiogenesis, and help re-establish a functional hair cycle in miniaturized follicles affected by AGA (Figure 2) [20]. While both AMT and exosomes-based therapies for AGA are categorised under regenerative based medicine, their mode of action and regulatory classifications differ substantially. Exosome treatments deliver pure isolated EVs from typically one type of cell, whereas micrografts deliver autologous and non-manipulated exosomes throughout the secretome of intact cell populations such as HF-MSCs and/or dermal cells.
Current clinical evidence on AMT consists primarily of non-randomised, single-arm and pilot studies with limited sample sizes and maximum of 12 months follow-up durations. Several of these early trials provide encouraging findings regarding the efficacy and safety of AMT, using the Regenera Activa® system, in the treatment of AGA. Krefft-Trzciniecka et al. (2024) [60] conducted an interventional study involving 23 female patients diagnosed with AGA (grades I to III on the Ludwig scale). Patients received a single treatment and were evaluated after six months using standardized photography and the Visual Analogue Scale (VAS) scored by four independent dermatologists. Results showed an average increase of 1.5 points in VAS and a one-grade improvement on the Ludwig scale, indicating notable visual improvement following treatment [60].
Similarly, Alvarez X. et al. (2017) [61] performed an interventional study on 17 patients treated with Regenera Activa®. Subjective patient assessments revealed that 82.3% of patients expressed moderate to high satisfaction with the treatment. Furthermore, 70.6% perceived an increase in hair thickness, while almost half of the patients (47.1%) noticed reduced hair loss [61].
Ruiz R.G. et al. (2019) [62] conducted a larger-scale study with 100 patients to assess the long-term effects of AMT. Using photographic analysis and TrichoScan® at 2-, 6-, and 12-months post-treatment, a significant improvement in hair density (+33.3 hairs/cm2) and thickness (+5.6%) was observed at two months. Histological evaluation with Mallory’s trichrome staining revealed a higher number of hair follicles, dermal papilla growth, and organized collagen structures at 6 to 9 months post-treatment, confirming active hair follicle regeneration and enhanced scalp architecture [62].
Gentile P. et al. (2020) [50] examined the use of autologous micrografts (with HF-MSCs) and PRP in improving hair re-growth in AGA, in two separate groups. Patients underwent evaluations at five intervals over a 23-week period. At the final follow-up, the treated areas, both with PRP and AMT, showed a 29 ± 5% increase in hair density, significantly outperforming the placebo regions, which exhibited less than 1% change [50]. These findings underscore the clinical efficacy of AMT vs. PRP in promoting follicular renewal and improving hair density.
Zari S. (2021) [63] evaluated the short-term effectiveness of a single Regenera Activa® session in 140 adults with confirmed AGA. TrichoScan analysis conducted between one and six months after treatment revealed statistically significant improvements in key parameters, including hair density (increase of 4.5 to 7.1 hairs/cm2), average hair shaft thickness (0.96 to 1.88 μm), cumulative hair thickness (0.48 to 0.56 units), and the number of follicular units (1.30 to 2.77). The frontal scalp region demonstrated the most consistent improvements, with reductions in negative indicators such as yellow dots and thin hair. Notably, male patients experienced greater gains in hair density, while female patients saw significant improvements in thickness and yellow dot reduction. Additionally, an increase in trichometry indicators was also observed in the occipital (donor) region of female patients, even though it was not the target treatment area—an effect that may have implications for future hair transplantation strategies [63].
The most recent study from Gentile P. et al. (2024) [64] shows significant clinical results with an increase in hair density of 28 ± 4 hairs/cm2 in FPHL with statistically significant difference in hair regrowth (p = 0.0429) and an increase of 30 ± 5 hairs/cm2 in MPHL with hair regrowth (p = 0.0012) at 12 months vs. baseline. In addition, the study shows the presence of EVs and their characterization as exosomes throughout quantitative and qualitative measurements, such as the mean diameter ranging from 95.9 nm to 123.2 nm and a concentration of 108 to 1010 particles/mL [64].
These preliminary studies support the efficacy and safety of Regenera Activa® in treating AGA and promoting hair regrowth, although more research is necessary to make definitive conclusions. Consistent improvements have been observed across objective trichometry parameters, histopathological findings, and patient-reported outcomes, highlighting AMT as a regenerative medicine point-of-care approach for both male and female patients affected by the most prevalent form of hair loss [65]. Further controlled, blinded, long-term trials are needed to confirm benefits and indications of Regenera Activa®.
Table 2. Summary of studies of autologous micrografting technology for androgenetic alopecia.
Table 2. Summary of studies of autologous micrografting technology for androgenetic alopecia.
No.StudyYearBrief DescriptionSample Size & Study DesignFindings
1Trovato, Letizia et al. [66]2015In vitro preclinical validation of Regenera®, demonstrating the viability and characterization of stem cell populations into 80 µm micrografts 23 samples, All samples were tested for cell viability and cell characterization throughout flow cytometry analysis (FACS) with antibodies and 7AAD stainingIn vitro, the presence of MSCs with expression of CD90 (52%), CD105 (82%) and CD73 (82%). Cell viability in all tissue samples is over 70%, up to 100%.
2Álvarez, X., Valenzuela, & M., Tuffet, J. [61]2017Pilot study evaluating the Regenera® technology for treating AGA through microscopic and histologic analyses for grade III–IV of alopecia Hamilton scale.3 patients with male pattern AGA., Results were measured 30 days post-treatment with a micrometer (for hair thickness), hair loss test, and biopsy for identification of cells in the proliferative phase of the cell cycle.The microscopic results showed an increase in hair thickness and a reduction in hairreduction of hair loss. The histological results showed an increase in epidermis thickness, the number of blood vessels and fibroblastic activity in the hair bulb.
3Álvarez, X., Valenzuela, & M., Tuffet, J. [67]2017The clinical and histological evaluation of the Regenera® method for AGA treatment showed promising results, including increased hair density and follicle regeneration.17 patients with AGA (9 with MPHL and 8 with FPHL). Variables assessed after 30 days post-AMT with picture comparison and improving according to Hamilton and Ludwig scale.An increase in hair thickness in 70% of the patients, 50% of the patients observed a decrease in hair loss. The perception of pain during the treatment was evaluated by most of the patients as level 3 out of 10.
4Pinto, H., Gálvez, R., & Casanova, J. [68]2018The article highlights the importance of dermatoscopy in predicting the outcomes for AGA using the Regenera® protocol.Review of 100 dermoscopies, the aim of this study was to establish an algorithm based on the 8 most important trichoscopic parameters and guideline to select the patients for AMT.Scalp dermascopic measurements used to propose an easy score system and algorithm for treating different patient profiles with AGA.
5Gentile, Pietro et al. [48]2019The study evaluated the clinical outcomes of autologous micrografts (with HF-MSCs) vs. Placebo in AGA. A randomized, long-term, evaluator-blinded, half-head group study.27 patients, 17 males with Hamilton II–VI and 10 females Ludwig I–II. Clinical Evaluation of hair regrowth using phototrichograms. Histological evaluation of the skin biopsies for viability and quantity of the cells.Improvement shown in the hair cumulative mean after 58 weeks of 18 hairs more vs. baseline. A total hair density increase of 23.3 hairs/cm2 vs. baseline. Characterization was made of HF-MSCs and mean quantity of 4124.7 cells. With the highest % of CD44+ cells from dermal papilla.
6Ruiz, R. G. et al. [62]2019The study explored the use of progenitor-cell-enriched micrografts from the dermis in the treatment of AGA by clinical and histological evaluations after 4, 6 and 12 months.100 patients with AGA were treated with AMT and assessed with TrichoScan Test and histological evaluation of the biopsies was performed.The TrichoScan Analysis reported a mean increase in total hair density of 30% after 2 months post-treatment and a 10% increase in anagen hairs.
7Zari S. [63]2021A retrospective cohort study assessed the short-term efficacy of autologous cellular micrografts in treating AGA in 140 patients, both males and females.140 patients with AGA (male and female). Efficacy was evaluated at 1 and 6 months by trichometry parameters (TrichoScan).The results showed an increase in mean hair density by 4.5–7.12 hair/cm2. average hair thickness by 0.96–1.88 μm, % thick hair by 1.74–3.26%, and mean number of follicular units by 1.30–2.77, resulting in an increase in cumulative hair thickness by 0.48–0.56 unit.
8Hawwam, S. A., Ismail, M., & Elhawary, E. [69]2023This study evaluated the effectiveness of autologous micrograft injections from scalp tissue in treating COVID-19-associated telogen effluvium.20 female patients. Patients were evaluated at the beginning, after 3 and 6 months post-treatment. The evaluation was based on changes in hair density and hair thickness and global photographic assessment.11, 6 and 3 patients presented marked clinical improvement, moderate and mild improvement, respectively. Hair density/cm2 mean was 184.1 (T0) vs. 192.9 (T6). Hair thickness (mm) 0.06 (T0) vs. 0.08 (T6).
9Krefft-Trzciniecka K. et al. [60]2024The clinical assessment focused on treating female AGA with autologous stem cells derived from human hair follicles.23 patients with AGA (Ludwig grade I–III). The aim of the study was to evaluate the clinical effect of AMT based on images before and 6 months after the treatment. A significant improvement was observed on the visual analog scale (VAS) when comparing pre- and post-procedure photos (p < 0.001).
10Vincenzi, C., Cameli, N., Pessei, V., Tosti, A. [70]2024The study highlighted the use of the Regenera® system for autologous micrografting in AGA treatment. Patients reported satisfactory hair improvement and treatment tolerability, indicating this regenerative approach as a promising tool for clinicians.Combination of 2 studies involving the analysis of 30 patients in total. 17 patients with 1 time AMT/year vs. 13 patients with 2 times AMT/year. Clinical assessment with global photography using TrichoLab and patient satisfaction.After 3 months versus baseline, hair diameter increases by 7.35% +/−1.89% (p < 1%). After 6 months versus baseline, hair diameter increases by 5.23% +/−1.78% (p < 1%). 69% (9/13) of the patients revealed an improvement. No statistically significant outcomes were seen 1 time AMT group vs. 2 times AMT.
11Gentile, P. et al. [64] 2025This multicentric, observational, evaluator-blinded study analysed autologous micrografts containing nanovesicles, exosomes, and follicle stem cells for AGA treatment.83 patients (52 with MPHL and 31 with FPHL). The treated patients were 60. Hair regrowth was evaluated with photography, physician’s and patient’s global assessment scales and phototrichograms at 1 year follow-up. In vitro analysis was performed through quantitative, morphological and size characterization of EVs with TEM and fluorescent microscopy.A hair density (HD) increases of 28 ± 4 hairs/cm2 at T4 (12 months) vs. baseline in FPHL. In MPHL, an HD increase of 30 ± 5 hairs/cm2 at T4 (12 months) with an SSD in hair regrowth (p = 0.0012). The presence of EVs and their interaction with the surrounding cellular population were demonstrated.

3.5. Comparison of Regenerative Treatments

Although the aforementioned regenerative approaches may open the door to a very promising landscape in which AGA can be managed in an easier and non-drug dependent way, they differ in the source tissue, protocol, invasive profile, and costs (Table 3). In terms of the treatment protocol, PRP requires several sessions that might compromise patient compliance. However, it is the least invasive treatment compared to AT-MSCs and AMT, as it only requires blood extraction. When considering methods of preparation, AMT is faster and easier to standardise than the others. AT-MSCs is probably the most invasive procedure, as it requires extraction of adipose tissue from subcutaneous tissue. These approaches, although promising, share similar boundaries. They need more consistent and reproducible evidence to prove efficacy and they require procedure standardization.

4. Discussion

This review synthesizes the available clinical and mechanistic evidence over the past decade, highlighting the rapid evolution of regenerative approaches for the management of AGA. A review of regenerative treatments by Alves and Grimalt [71]. suggests PRP remains the most evidence-based option, supported by several randomized controlled trials and meta-analyses demonstrating consistent efficacy and safety profiles [72,73,74]. This stronger evidence base likely reflects PRP’s longer clinical use, wider accessibility, and lower cost compared to other regenerative interventions. By contrast, therapies such as exosome-based formulations, adipose-derived stem cell procedures, and AMT have gained popularity and market presence only in the past five years, which partly explains the limited number of high-quality, independent clinical studies currently available.
Encouraging results have been reported for AMT, with improvements in cumulative hair thickness of up to 0.56 units, hair shaft thickness increases of approximately 3.26%, and mean hair density gains of up to 7.12 hairs/cm2 [63]. However, it is essential to recognize that the majority of these studies are non-randomized, single-centre pilot investigations with relatively small sample sizes and short follow-up durations. Robust randomized controlled trials with appropriate blinding and independent assessment are still lacking. AMT (by Rigenera®) can be described as a complex biologically active autologous micrograft system, yet its precise mechanisms of action in hair follicle regeneration remain incompletely understood, and independent molecular validation in human tissue is warranted.
Beyond the specific limitations of the study designs with AMT, the field of hair restoration also faces significant challenges in standardisation. Currently, there is no unified regulatory or methodological framework guiding the clinical development of regenerative medicine-based devices and procedures for hair restoration. Establishing clear guidelines would enable the generation of more uniform and comparable data across studies and products, including the definition of mandatory outcome parameters for assessing follicular regeneration and hair growth. Moreover, classifying treatments according to their biological source (autologous vs. allogenic) and the degree of tissue manipulation (minimal vs. substantial) would improve transparency and reproducibility.
Clinical intervariability remains another critical issue especially in autologous procedures. Outcomes may vary depending on patient-specific factors such as biological age, tissue quality, hormonal status, and overall systemic health, as well as on operator technique and device calibration. Future research should aim to develop predictive tools or metrics that account for these biological and procedural variables, thereby improving patient selection and individualising treatment protocols. Addressing these challenges through rigorous clinical design, harmonised standards, and reproducibility-focused studies will be essential to advance not only AMT but also the other regenerative options toward validated, evidence-based integration into routine clinical practice.

5. Conclusions

Regenerative medicine-based modalities in hair restoration are rapidly expanding. Future research in this field should prioritise not only the implementation of multicentric, randomised, and controlled blinded clinical trials but also the establishment of uniform and standardised clinical guidelines that define methodological frameworks for hair research. Such harmonisation is essential to ensure consistency in study design, data collection, and interpretation across the various regenerative approaches. Standardised guidelines would not only facilitate collaboration among researchers, clinicians, and industry stakeholders but also support the generation of robust, comparable evidence. Ultimately, this coordinated effort is vital to accelerate the development and clinical translation of safe, effective, and reproducible regenerative therapies for patients with androgenetic alopecia.

Author Contributions

Conceptualization, A.T., A.I., M.H. and C.V.; writing—original draft preparation, V.W., A.I. and M.H.; writing—reviewing and editing, V.W., A.T., A.I., M.H. and C.V.; visualization, A.I., M.H. and C.V. All authors have read and agreed to the published version of the manuscript.

Funding

The Article Publishing Charge was funded by Regenera Activa, Barcelona, Spain.

Conflicts of Interest

Antonella Tosti—Consultant: DS Laboratories, Almirall, Tirthy Madison, Eli Lilly, Pfizer, Myovant, Bristol Myers Squibb, Ortho Dermatologics, Sun Pharmaceuticals, Abbvie, WellBeauty Company LLC, L’Oreal/Vichy USA, Amgen LLC, Veradermics; Antoniya Ivanova—Medical Advisor, Regenera Activa Worldwide, Barcelona, Spain.

References

  1. Liu, Y.; Tosti, A.; Wang, E.; Heilmann-Heimbach, S.; Aguh, C.; Jimenez, F.; Sung-Jan, L.; Kwon, O.; Plikus, M. Androgenetic alopecia. Nat. Rev. Dis. Primers 2025, 11, 73. [Google Scholar] [CrossRef]
  2. He, F.; Shen, M.; Zhao, Z.; Liu, Y.; Zhang, S.; Tang, Y.; Xie, H.; Chen, X.; Li, J. Epidemiology and disease burden of androgenetic alopecia in college freshmen in China: A population-based study. PLoS ONE 2022, 17, e0263912. [Google Scholar] [CrossRef]
  3. Norwood, O.T. Male pattern baldness: Classification and incidence. South Med. J. 1975, 68, 1359–1365. [Google Scholar] [CrossRef]
  4. Ludwig, E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br. J. Dermatol. 1977, 97, 247–254. [Google Scholar] [CrossRef]
  5. Ingrassia, J.; Buontempo, M.; Alhanshali, L.; Akoh, C.; Glick, S.; Shapiro, J.; Lo Sicco, K. The financial burden of alopecia: A survey study. Int. J. Women’s Dermatol. 2023, 9, e118. [Google Scholar] [CrossRef] [PubMed]
  6. Nestor, M.S.; Ablon, G.; Gade, A.; Han, H.; Fischer, D.L. Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics. J. Cosmet. Dermatol. 2021, 20, 3759–3781. [Google Scholar] [CrossRef]
  7. Zhou, Z.; Cui, Y.; Wu, J.; Jin, H. Efficacy and safety of dutasteride compared with finasteride in treating males with benign prostatic hyperplasia: A meta-analysis of randomized controlled trials. Exp. Ther. Med. 2020, 20, 1566–1574. [Google Scholar] [CrossRef] [PubMed]
  8. Egger, A.; Tomic-Canic, M.; Tosti, A. Advances in Stem Cell-Based Therapy for Hair Loss. CellR4 Repair Replace. Regen. Reprogramming 2020, 8, e2894. [Google Scholar]
  9. Ohyama, M. Hair follicle bulge: A fascinating reservoir of epithelial stem cells. J. Dermatol. Sci. 2007, 46, 81–89. [Google Scholar] [CrossRef] [PubMed]
  10. Geyfman, M.; Plikus, M.V.; Treffeisen, E.; Andersen, B.; Paus, R. Resting no more: Re-defining telogen, the maintenance stage of the hair growth cycle. Biol. Rev. Camb. Philos. Soc. 2015, 90, 1179–1196. [Google Scholar] [CrossRef]
  11. Lolli, F.; Pallotti, F.; Rossi, A.; Fortuna, M.; Caro, G.; Lenzi, A.; Sansone, A.; Lombardo, F. Androgenetic alopecia: A review. Endocrine 2017, 57, 9–17. [Google Scholar] [CrossRef]
  12. Cuevas-Diaz Duran, R.; Martinez-Ledesma, E.; Garcia-Garcia, M.; Gauzin, D.; Sarro-Ramírez, A.; Gonzalez-Carillo, C.; Rodríguez-Sardin, D.; Fuentes, A.; Cardenas-Lopez, A. The Biology and Genomics of Human Hair Follicles: A Focus on Androgenetic Alopecia. Int. J. Mol. Sci. 2024, 25, 2542. [Google Scholar] [CrossRef] [PubMed]
  13. Pirastu, N.; Joshi, P.K.; de Vries, P.S.; Cornelis, M.; McKeigue, P.; Keum, N.; Franceschini, N.; Colombo, M.; Giovannuci, e.; Spiliopoulou, A.; et al. GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk. Nat. Commun. 2017, 8, 1584. [Google Scholar] [CrossRef]
  14. Trüeb, R.M. Molecular mechanisms of androgenetic alopecia. Exp. Gerontol. 2002, 37, 981–990. [Google Scholar] [CrossRef]
  15. Cellular Senescence: Ageing and Androgenetic Alopecia—PubMed. Available online: https://pubmed-ncbi-nlm-nih-gov.proxy.westernu.edu/37088073/ (accessed on 24 August 2025).
  16. Leirós, G.J.; Attorresi, A.I.; Balañá, M.E. Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia. Br. J. Dermatol. 2012, 166, 1035–1042. [Google Scholar] [CrossRef]
  17. Chen, X.; Liu, B.; Li, Y.; Han, L.; Tang, X.; Deng, W.; Lai, W.; Wan, M. Dihydrotestosterone Regulates Hair Growth Through the Wnt/β-Catenin Pathway in C57BL/6 Mice and In Vitro Organ Culture. Front. Pharmacol. 2019, 10, 1528. [Google Scholar] [CrossRef] [PubMed]
  18. Inui, S.; Itami, S. Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla. J. Dermatol. Sci. 2011, 61, 1–6. [Google Scholar] [CrossRef]
  19. Vañó, S.; Jaén, P. Practical Handbook of Hair Disorders #TricoHRC, 2nd ed.; Instituto Ramón y Cajal de Investigación Sanitaria: Madrid, Spain, 2023. [Google Scholar]
  20. Oiwoh, S.O.; Enitan, A.O.; Adegbosin, O.T.; Akinboro, A.O.; Onayemi, E.O. Androgenetic Alopecia: A Review. Niger. Postgrad. Med. J. 2024, 31, 85–92. [Google Scholar] [CrossRef]
  21. Xiong, H.D.; Tang, L.L.; Chen, H.J.; Wu, Y.; Li, W.Y.; Wen, S.J.; Lin, Y.K. Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia. Medicine 2023, 102, e35242. [Google Scholar] [CrossRef]
  22. Gheisari, M.; Hamidi, A.B.; Hamedani, B.; Zerehpoush, F.B. Androgenetic alopecia; An attempt to target microinflammation. Dermatol. Ther. 2020, 33, e13266. [Google Scholar] [CrossRef] [PubMed]
  23. Mahé, Y.F.; Michelet, J.F.; Billoni, N.; Jarrousse, F.; Buan, B.; Commo, S.; Saint-Léger, D.; Bernard, B. Androgenetic alopecia and microinflammation. Int. J. Dermatol. 2000, 39, 576–584. [Google Scholar] [CrossRef]
  24. Ho, C.Y.; Chen, J.Y.F.; Hsu, W.L.; Yu, S.; Chen, W.C.; Chiu, S.H.; Yang, H.R.; Lin, S.Y.; Wu, C.Y. Female Pattern Hair Loss: An Overview with Focus on the Genetics. Genes 2023, 14, 1326. [Google Scholar] [CrossRef] [PubMed]
  25. Devjani, S.; Ezemma, O.; Kelley, K.J.; Stratton, E.; Senna, M. Androgenetic Alopecia: Therapy Update. Drugs 2023, 83, 701–715. [Google Scholar] [CrossRef]
  26. Xing, H.; Peng, H.; Yang, Y.; Lv, K.; Zhou, S.; Pan, X.; Wang, J.; Hu, Y.; Li, G.; Ma, D. Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy. Bioact. Mater. 2024, 32, 190–205. [Google Scholar] [CrossRef]
  27. Akiska, Y.M.; Mirmirani, P.; Roseborough, I.; Mathes, E.; Bhutani, T.; Ambrosy, A.; Aguh, C.; Bergfeld, W.; Callender, V.; Castelo-Soccio, L.; et al. Low-Dose Oral Minoxidil Initiation for Patients With Hair Loss: An International Modified Delphi Consensus Statement. JAMA Dermatol. 2025, 161, 87–95. [Google Scholar] [CrossRef]
  28. Shen, Y.; Zhu, Y.; Zhang, L.; Sun, J.; Xie, B.; Zhang, H.; Song, X. New Target for Minoxidil in the Treatment of Androgenetic Alopecia. Drug Des. Devel. Ther. 2023, 17, 2537–2547. [Google Scholar] [CrossRef]
  29. Sharma, A.; Goren, A.; Dhurat, R.; Agrawal, S.; Sinclair, R.; Trüeb, R.; Vañó-Galván, S.; Chen, G.; Tan, Y.; Kovacevic, M.; et al. Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes. Dermatol. Ther. 2019, 32, e12915. [Google Scholar] [CrossRef]
  30. Chitalia, J.; Dhurat, R.; Goren, A.; McCoy, J.; Kovacevic, M.; Situm, M.; Naccarato, T.; Lotti, T. Characterization of follicular minoxidil sulfotransferase activity in a cohort of pattern hair loss patients from the Indian Subcontinent. Dermatol. Ther. 2018, 31, e12688. [Google Scholar] [CrossRef] [PubMed]
  31. Goren, A.; Castano, J.A.; McCoy, J.; Bermudez, F.; Lotti, T. Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia. Dermatol. Ther. 2014, 27, 171–173. [Google Scholar] [CrossRef]
  32. Adil, A.; Godwin, M. The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis. J. Am. Acad. Dermatol. 2017, 77, 136–141.e5. [Google Scholar] [CrossRef] [PubMed]
  33. DailyMed—PROPECIA-Finasteride Tablet, Film Coated. Available online: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6f904709-65aa-44ce-b144-b4c8a0416e36 (accessed on 24 August 2025).
  34. Kaufman, K.D.; Dawber, R.P. Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia. Expert Opin. Investig. Drugs 1999, 8, 403–415. [Google Scholar] [CrossRef]
  35. Drake, L.; Hordinsky, M.; Fiedler, V.; Swinehart, J.; Unger, W.P.; Cotterill, P.C.; Thiboutot, D.M.; Lowe, N.; Jacobson, C.; Whiting, D.; et al. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J. Am. Acad. Dermatol. 1999, 41, 550–554. [Google Scholar] [PubMed]
  36. Zhang, J.J.; Shi, X.; Wu, T.; Zhang, M.D.; Tang, J.; Yin, G.M.; Long, Z.; He, L.Y.; Qi, L.; Wang, L. Sexual, physical, and overall adverse effects in patients treated with 5α-reductase inhibitors: A systematic review and meta-analysis. Asian J. Androl. 2022, 24, 390–397. [Google Scholar] [CrossRef]
  37. Traish, A.M. Post-finasteride syndrome: A surmountable challenge for clinicians. Fertil. Steril. 2020, 113, 21–50. [Google Scholar] [CrossRef]
  38. Olsen, E.A.; Hordinsky, M.; Whiting, D.; Stough, D.; Hobbs, S.; Ellis, M.; Wilson, T.; Rittmaster, R. The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: Results of a randomized placebo-controlled study of dutasteride versus finasteride. J. Am. Acad. Dermatol. 2006, 55, 1014–1023. [Google Scholar] [CrossRef]
  39. Gubelin Harcha, W.; Barboza Martínez, J.; Tsai, T.F.; Katsuoka, K.; Kawashima, M.; Tsuboi, R.; Barnes, A.; Ferron-Brady, G.; Chetty, D. A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia. J. Am. Acad. Dermatol. 2014, 70, 489–498.e3. [Google Scholar] [CrossRef]
  40. Dhurat, R.; Sharma, A.; Rudnicka, L.; Kroumpouzos, G.; Kassir, M.; Galadari, H.; Wollina, U.; Lotti, T.; Golubovic, M.; Binic, I.; et al. 5-Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms, current concepts, comparative efficacy, and safety. Dermatol. Ther. 2020, 33, e13379. [Google Scholar] [CrossRef] [PubMed]
  41. Pozo-Pérez, L.; Tornero-Esteban, P.; López-Bran, E. Clinical and preclinical approach in AGA treatment: A review of current and new therapies in the regenerative field. Stem Cell Res. Ther. 2024, 15, 260. [Google Scholar] [CrossRef] [PubMed]
  42. Wang, X.Y.; Han, X.J.; Wu, J.; Yuan, Q.Y.; Zhou, J.; Yu, Z.P.; Han, X.H.; Guan, X.H. Single-Cell RNA Sequencing Highlights a Contribution of Human Amniotic Mesenchymal Stem Cells-Derived Exosomes to Androgenetic Alopecia. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2025, 39, e70820. [Google Scholar] [CrossRef]
  43. Marks, P.; Gottlieb, S. Balancing Safety and Innovation for Cell-Based Regenerative Medicine. N. Engl. J. Med. 2018, 378, 954–959. [Google Scholar] [CrossRef]
  44. Finnoff, J.T.; Awan, T.M.; Borg-Stein, J.; Harmon, K.G.; Herman, D.C.; Malanga, G.; Master, Z.; Mautner, K.; Shapiro, S. American Medical Society for Sports Medicine Position Statement: Principles for the Responsible Use of Regenerative Medicine in Sports Medicine. Clin. J. Sport Med. Off. J. Can. Acad. Sport Med. 2021, 31, 530–541. [Google Scholar] [CrossRef]
  45. Abdin, R.; Zhang, Y.; Jimenez, J.J. Treatment of Androgenetic Alopecia Using PRP to Target Dysregulated Mechanisms and Pathways. Front. Med. 2022, 9, 843127. [Google Scholar] [CrossRef]
  46. Stevens, J.; Khetarpal, S. Platelet-rich plasma for androgenetic alopecia: A review of the literature and proposed treatment protocol. Int. J. Womens Dermatol. 2019, 5, 46–51. [Google Scholar] [CrossRef]
  47. Camila Ospina Rios, M. The role of platelet-rich plasma in androgenetic alopecia: A comprehensive narrative review. Glob. J. Res. Anal. 2023, 12, 62–63. [Google Scholar] [CrossRef]
  48. Gentile, P.; Scioli, M.G.; Bielli, A.; Angelis, B.; De Sio, C.; De Fazio, D.; Ceccarelli, G.; Trivisonna, A.; Orlandi, A.; Cervelli, V.; et al. Platelet-Rich Plasma and Micrografts Enriched with Autologous Human Follicle Mesenchymal Stem Cells Improve Hair Re-Growth in Androgenetic Alopecia. Biomolecular Pathway Analysis and Clinical Evaluation. Biomedicines 2019, 7, 27. [Google Scholar] [CrossRef]
  49. Gupta, A.K.; Carviel, J.L. Meta-analysis of efficacy of platelet-rich plasma therapy for androgenetic alopecia. J. Dermatol. Treat. 2017, 28, 55–58. [Google Scholar] [CrossRef] [PubMed]
  50. Gentile, P.; Garcovich, S. Systematic Review of Platelet-Rich Plasma Use in Androgenetic Alopecia Compared with Minoxidil®, Finasteride®, and Adult Stem Cell-Based Therapy. Int. J. Mol. Sci. 2020, 21, 2702. [Google Scholar] [CrossRef] [PubMed]
  51. Shapiro, J.; Ho, A.; Sukhdeo, K.; Yin, L.; Sicco, K.L. Evaluation of platelet-rich plasma as a treatment for androgenetic alopecia: A randomized controlled trial. J. Am. Acad. Dermatol. 2020, 83, 1298–1303. [Google Scholar] [CrossRef] [PubMed]
  52. Liang, Y.; Tang, X.; Zhang, X.; Cao, C.; Yu, M.; Wan, M. Adipose Mesenchymal Stromal Cell-Derived Exosomes Carrying MiR-122-5p Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicles by Targeting the TGF-β1/SMAD3 Signaling Pathway. Int. J. Mol. Sci. 2023, 24, 5703. [Google Scholar] [CrossRef]
  53. Ma, C.; Cheng, M.; Xiao, T.; Qi, R.; Gao, X.; Chen, H.; Wu, Y.; Xu, X. miR-574-3p and miR-125a-5p in Adipose-Derived Mesenchymal Stem Cell Exosomes Synergistically Target TGF-β1/SMAD2 Signaling Pathway for the Treatment of Androgenic Alopecia. J. Investig. Dermatol. 2025, 145, 2719–2735.e3. [Google Scholar] [CrossRef]
  54. Yan, W.; Liu, J.; Xie, X.; Jin, Q.; Yang, Y.; Pan, Y.; Zhang, Y.; Zhang, F.; Wang, Y.; Liu, J.; et al. Restoration of follicular β-catenin signaling by mesenchymal stem cells promotes hair growth in mice with androgenetic alopecia. Stem Cell Res. Ther. 2024, 15, 439. [Google Scholar] [CrossRef] [PubMed]
  55. Shimizu, Y.; Ntege, E.H.; Sunami, H.; Inoue, Y. Regenerative medicine strategies for hair growth and regeneration: A narrative review of literature. Regen. Ther. 2022, 21, 527–539. [Google Scholar] [CrossRef]
  56. Jia, Y.; Yu, L.; Ma, T.; Xu, W.; Zian, H.; Sun, Y.; Shi, H. Small extracellular vesicles isolation and separation: Current techniques, pending questions and clinical applications. Theranostics 2022, 12, 6548–6575. [Google Scholar] [CrossRef]
  57. Zhang, H.; Yao, J.; Jiang, Q.; Shi, Y.; Ge, W.; Xu, X. Engineered Exosomes Biopotentiated Hydrogel Promote Hair Follicle Growth via Reprogramming the Perifollicular Microenvironment. Pharmaceutics 2024, 16, 935. [Google Scholar] [CrossRef] [PubMed]
  58. Liu, Y.; Liu, Y.; Zhao, J.; Deng, T.; Ben, Y.; Lu, R.; Zhou, X.; Yan, R.; Chen, X.; Zhang, J.; et al. Subcutaneous injection of genetically engineered exosomes for androgenic alopecia treatment. Front. Bioeng. Biotechnol. 2025, 13, 1614090. [Google Scholar] [CrossRef]
  59. Queen, D.; Avram, M.R. Exosomes for Treating Hair Loss: A Review of Clinical Studies. Dermatol. Surg. 2025, 51, 409–415. [Google Scholar] [CrossRef]
  60. Krefft-Trzciniecka, K.; Piętowska, Z.; Pakiet, A.; Nowicka, D.; Szepietowski, J.C. Short-Term Clinical Assessment of Treating Female Androgenetic Alopecia with Autologous Stem Cells Derived from Human Hair Follicles. Biomedicines 2024, 12, 153. [Google Scholar] [CrossRef]
  61. Álvarez, X.; Valenzuela, M.; Tuffet, J. Clinical and Histological Evaluation of the Regenera® Method for the Treatment of Androgenetic Alopecia. Int. Educ. Appl. Sci. Res. J. 2018, 3, 2456–5040. [Google Scholar]
  62. Ruiz, R.G.; Rosell, J.M.C.; Ceccarelli, G.; De Sio, C.; De Angelis, G.; Pinto, H.; Astarita, C.; Graziano, A. Progenitor-cell-enriched micrografts as a novel option for the management of androgenetic alopecia. J. Cell Physiol. 2019, 235, 4587–4593. [Google Scholar] [CrossRef] [PubMed]
  63. Zari, S. Short-Term Efficacy of Autologous Cellular Micrografts in Male and Female Androgenetic Alopecia: A Retrospective Cohort Study. Clin. Cosmet. Investig. Dermatol. 2021, 14, 1725–1736. [Google Scholar] [CrossRef]
  64. Gentile, P.; Garcovich, S.; Perego, F.; Arsiwala, N.; Faruk Yavuz, M.; Pessei, V.; Pusceddu, T.; Zavan, B.; Arsiwala, S. Autologous Micrografts Containing Nanovesicles, Exosomes, and Follicle Stem Cells in Androgenetic Alopecia: In Vitro and In Vivo Analysis Through a Multicentric, Observational, Evaluator-Blinded Study. Aesthetic Plast. Surg. 2025, 49, 43–58. [Google Scholar] [CrossRef] [PubMed]
  65. Astarita, C.; Arora, C.L.; Trovato, L. Tissue regeneration: An overview from stem cells to micrografts. J. Int. Med. Res. 2020, 48, 300060520914794. [Google Scholar] [CrossRef]
  66. Trovato, L.; Monti, M.; del Fante, C.; Cervio, M.; Lampinen, M.; Ambrosio, L.; Redi, C.A.; Perotti, C.; Kankuri, E.; Ambrosio, G.; et al. A New Medical Device Rigeneracons Allows to Obtain Viable Micro-Grafts From Mechanical Disaggregation of Human Tissues. J. Cell Physiol. 2015, 230, 2299–2303. [Google Scholar] [CrossRef]
  67. Álvarez, X.; Valenzuela, M.; Tuffet, J. Microscopic and Histologic Evaluation of the Regenera method for the Treatment of Androgenetic Alopecia in a Small Number of Cases. Int. J. Res. Studies Med. Health Sci. 2017, 2, 19–22. [Google Scholar]
  68. Hernán, P.; Rafael, G.; José, C. Dermoscopy Is the Crucial Step for Proper Outcome Prospection When Treating Androgenetic Alopecia with the Regenera® Protocol: A Score Proposal. Int. J. Clin. Dev. Anat. 2018, 4, 15–18. [Google Scholar] [CrossRef]
  69. Hawwam, S.; Ismail, M.; Elhawary, E. The Role of Autologous Micrografts Injection from The Scalp Tissue in The Treatment of COVID-19 Associated Telogen Effluvium: Clinical and Trichoscopic Evaluation. Dermatol. Ther. 2022, 35, e15545. [Google Scholar] [CrossRef]
  70. Vincenzi, C.; Cameli, N.; Pessei, V.; Tosti, A. Role of Autologous Micrografting Technology through Rigenera® System in the Treatment of Androgenetic Alopecia. Skin Appendage Disord. 2025, 11, 119–127. [Google Scholar] [CrossRef]
  71. Alves, R.; Grimalt, R. A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord. 2018, 4, 18–24. [Google Scholar] [CrossRef]
  72. Georgescu, S.; Amuzescu, A.; Mitran, C.; Mitran, M.; Matei, C.; Constantin, C.; Tampa, M.; Neagu, M. Eficàcia de la teràpia amb plasma ric en plaquetes en l’alopècia androgènica: Una metaanàlisi. J. Pers. Med. 2022, 12, 342. [Google Scholar] [CrossRef]
  73. Gupta, A.; Cole, J.; Deutsch, D.; Everts, P.; Niedbalski, R.; Panchaprateep, R.; Rinaldi, F.; Rose, P.; Sinclair, R.; Vogel, J.; et al. Plasma ric en plaquetes com a tractament per a l’alopècia androgenètica. Dermatol. Surg. 2019, 45, 1262–1273. [Google Scholar] [CrossRef]
  74. Mysore, V.; Alexander, S.; Nepal, S.; Venkataram, A. Regenerative Medicine Treatments for Androgenetic Alopecia. Indian J Plast. Surg. 2021, 54, 514–520. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
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Figure 1. Various types of exosomes and their sources including plant, animal, and human-derived.
Figure 1. Various types of exosomes and their sources including plant, animal, and human-derived.
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Figure 2. Mechanism of Action of Autologous Micrografting Technology (AMT) in Androgenetic Alopecia (AGA). The figure illustrates the transition from an AGA-affected follicle to a healthier follicular environment following treatment with Autologous Micrografting Technology (AMT). On the left, the AGA-affected follicle is characterized by miniaturization and pathological factors such as DHT sensitivity, microinflammation, micronutrient deficiency, and genetic predisposition. The central component highlights the AMT system, which mechanically processes occipital scalp tissue to produce a suspension rich in regenerative elements, including hair follicle-derived mesenchymal stem cells, extracellular matrix, exosomes, growth factors, and cytokines—the so-called “AMT® Triad”. These micrografts act locally to reestablish follicular homeostasis by modulating inflammation, activating the Wnt/β-catenin pathway, and stimulating angiogenesis. On the right, the treated follicle exhibits improved vascularization and restored functionality, transitioning to a normalized hair growth cycle. AMT® Triad = AMT® suspension.
Figure 2. Mechanism of Action of Autologous Micrografting Technology (AMT) in Androgenetic Alopecia (AGA). The figure illustrates the transition from an AGA-affected follicle to a healthier follicular environment following treatment with Autologous Micrografting Technology (AMT). On the left, the AGA-affected follicle is characterized by miniaturization and pathological factors such as DHT sensitivity, microinflammation, micronutrient deficiency, and genetic predisposition. The central component highlights the AMT system, which mechanically processes occipital scalp tissue to produce a suspension rich in regenerative elements, including hair follicle-derived mesenchymal stem cells, extracellular matrix, exosomes, growth factors, and cytokines—the so-called “AMT® Triad”. These micrografts act locally to reestablish follicular homeostasis by modulating inflammation, activating the Wnt/β-catenin pathway, and stimulating angiogenesis. On the right, the treated follicle exhibits improved vascularization and restored functionality, transitioning to a normalized hair growth cycle. AMT® Triad = AMT® suspension.
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Table 1. Characteristic signs of AGA on trichoscopy analysis.
Table 1. Characteristic signs of AGA on trichoscopy analysis.
MPHLFPHL
Anisotrichosis (>20% miniaturized hair)Anisotrichosis (>10% miniaturized hair)
Peripilar sign (local microinflammation)Lower diameter of hair shafts in the frontal area vs. occipital area
Decreased number of hair shaftsYellow dots
Yellow dotsIncrease in the follicular units with one single hair shaft
Focal atrichia (loss of follicular units)
Table 3. Comparison of regenerative treatments including PRP, AT-MSCs, ADSVCs, ADRCs, exosomes, and AMT.
Table 3. Comparison of regenerative treatments including PRP, AT-MSCs, ADSVCs, ADRCs, exosomes, and AMT.
TreatmentSource TissueInvasive Profile/Method of ExtractionNumber of SessionsProtocol Type
PRPBloodMinimally/blood extraction3–5 sessionsPoint-of-Care
AT-MSCsAdipose tissueHighly/liposuction4–6 sessionsLaboratory-dependant
ADSVCsAdipose tissue
Stromal Vascular Fraction		Highly/liposuction1–2 sessionsPoint-of Care
ADRCsAdipose tissue CellsHighly/liposuction1–2 sessionsPoint-of-Care
ExosomesSeveral (natural/synthetic)Depends on the source/cultivationLack of dataLaboratory-dependant
AMTScalpMinimally/tissue biopsy1 sessionPoint-of-Care
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MDPI and ACS Style

Wang, V.; Tosti, A.; Ivanova, A.; Huertas, M.; Vincenzi, C. A Decade of Autologous Micrografting Technology in Hair Restoration: A Review of Clinical Evidence and the Evolving Landscape of Regenerative Treatments. Cosmetics 2025, 12, 254. https://doi.org/10.3390/cosmetics12060254

AMA Style

Wang V, Tosti A, Ivanova A, Huertas M, Vincenzi C. A Decade of Autologous Micrografting Technology in Hair Restoration: A Review of Clinical Evidence and the Evolving Landscape of Regenerative Treatments. Cosmetics. 2025; 12(6):254. https://doi.org/10.3390/cosmetics12060254

Chicago/Turabian Style

Wang, Vera, Antonella Tosti, Antoniya Ivanova, Marta Huertas, and Colombina Vincenzi. 2025. "A Decade of Autologous Micrografting Technology in Hair Restoration: A Review of Clinical Evidence and the Evolving Landscape of Regenerative Treatments" Cosmetics 12, no. 6: 254. https://doi.org/10.3390/cosmetics12060254

APA Style

Wang, V., Tosti, A., Ivanova, A., Huertas, M., & Vincenzi, C. (2025). A Decade of Autologous Micrografting Technology in Hair Restoration: A Review of Clinical Evidence and the Evolving Landscape of Regenerative Treatments. Cosmetics, 12(6), 254. https://doi.org/10.3390/cosmetics12060254

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