In Vitro and In Vivo Models for Androgenetic Alopecia Drug Development

In this study, researchers presented a protocol for generating planar skin organoids from human induced pluripotent stem cells, which include hair follicles and other skin structures, offering a relevant in vitro model for investigating skin physiology, pathogen interactions, and drug responses.

This study observed that serotonin signaling promoted hair shaft elongation and upregulated hair growth-related genes in dermal papilla cells, suggesting its potential role in advancing alopecia therapy.

This review highlights the limitations of existing hair loss treatments like minoxidil and finasteride and suggests that future therapies may benefit from focusing on antibody and cell-based treatments, which offer targeted and potentially transformative options for managing hair loss disorders.

This review compiled and evaluated numerous studies on alopecia treatments, highlighting promising pharmacological strategies like JAK inhibitors for alopecia areata and advancements in regenerative medicine for androgenetic alopecia, while also stressing the importance of personalized, mechanism-targeted approaches for improved outcomes across different alopecia subtypes.

In this study, researchers found that specific genetic variations at loci rs1160312, rs6113491, and rs1041668 are independent risk factors for androgenetic alopecia in men, and these risks can be influenced by diet.

This research observed that oxytocin receptor agonists WAY267464 and LIT001 increased hair growth-related gene expression in human dermal papilla cells and significantly promoted hair follicle sprouting in vitro, suggesting their potential as hair growth agents targeting OXTR for alopecia treatment.

This review reports that low-dose oral minoxidil can cause hypertrichosis due to increased systemic absorption, and highlights the importance of patient-centered care to manage the psychosocial impacts of this side effect effectively.

This review discusses the increasing prevalence of alopecia in younger populations and outlines the need for better understanding its pathogenesis to develop effective treatments. It also examines current FDA-approved drugs and emerging small molecule compounds with potential anti-alopecia effects.

In this study, cinnamic acid was found to enhance hair growth in human dermal papilla cells and hair follicle organoids by activating oxytocin signaling, suggesting its potential for developing hair growth-promoting products.

This study developed a new human in vitro hair model that replicates in vivo hair characteristics and may be suitable for high throughput screening of hair growth treatments.

This study reviews the regulatory mechanisms and molecular processes governing stem cell activity in hair follicles, highlighting their roles in hair regeneration and potential implications for treating hair and skin disorders.

In this study, researchers used a human skin organoid model to show that solar UV exposure damages hair follicles and skin, while exosomes from mesenchymal stem cells reduced inflammation and supported hair follicle regeneration.

This study explored the effects of oxytocin on hair growth and found that it upregulated growth-promoting factors in dermal papilla cells and hair follicle organoids, suggesting potential for developing new alopecia treatments.

In this study, researchers used 3D bioprinting to successfully create engineered skin tissues with hair follicle-like structures, potentially enhancing skin grafts and safety testing for chemical compounds by more closely mimicking natural skin complexity.

This study demonstrated that a mechanical-chemical cascade involving dermal cell contraction and the activation of Piezo1 in epidermal cells is crucial for initiating interactions necessary for hair follicle regeneration in skin organoids.

This review discusses the potential of low-dose oral minoxidil as a safe and effective treatment for certain hair disorders, including alopecia, but reports no new clinical results.

This study found that Y27632 treatment facilitated the formation of core-shell-shaped hair follicle organoids, resulting in nearly 100% efficient hair shaft sprouting in vitro.

This review highlights the limitations of mouse models in human hair loss research and emphasizes the potential of using human cell bioengineered models and artificial intelligence for future advancements, but reports no new clinical results.

In this study, the authors reported that oral dutasteride at 0.5 mg/day showed a probable greater efficacy in treating male androgenetic alopecia compared to finasteride and minoxidil, but it may cause sexual dysfunction and neuropsychiatric side effects.

This review discusses the formation and maintenance of hair follicles through dynamic cellular changes and signaling pathways, presenting a comprehensive overview but providing no new experimental findings.

This study successfully developed 3D hair follicle organoids from neonatal mouse epidermal and dermal cells, showing structural and molecular resemblance to native anagen hair follicles.

The study found that growing dermal papilla cells in 3D spheroids enhances their activity with hair growth-promoting agents, such as minoxidil and TCQA, compared to traditional 2D cultures.

This study reported that while topical minoxidil exhibits hair regrowth in androgenetic alopecia, oral minoxidil 5 mg/day was more effective than topical forms after six months, with low doses also potentially effective for women and other hair loss types.

This review discusses potential cell sources and bioengineering strategies for regenerating hair follicles with functional cycling, reporting no new results.

This review discusses recent advancements in generating appendage-bearing skin organoids from pluripotent stem cells and their potential applications in dermatological research, but reports no new clinical results.

This study introduced a simple and reliable in vitro assay capable of large-scale simultaneous screening of hair growth-promoting compounds using a 3D co-culture system of human dermal papilla and outer root sheath cells.

This study identified ten key hub genes and pathways crucial for understanding the molecular mechanism of hair growth by comparing dermal papilla cells in 2D and 3D cultures.

This review discusses the effects of hormonal changes on hair follicles, concluding that hormones like androgens and estradiol significantly influence hair growth and cycle, while the roles of other hormones are still being researched.

This study found that applying HHORSC exosomes may enhance the hair inductivity of dermal papilla cells, potentially improving treatments for hair loss.

Scientists created human skin with hair from stem cells, which could help treat hair loss and skin conditions.

This review discusses pharmacologic and non-pharmacologic treatments for androgenetic alopecia, noting that current medications like finasteride and minoxidil can slow hair loss but only partially restore hair growth, with early treatment offering better outcomes.

This review discusses the biology and signaling mechanisms of dermal papilla cells in hair follicle growth and reports no new clinical results; the authors emphasize the importance of optimizing culture conditions for hair restoration.

This review discusses the evidence for post-finasteride syndrome as a condition potentially induced by finasteride and dutasteride, associating them with sexual dysfunction, depression, anxiety, and suicidal ideation in a subset of men, and reports no new clinical results.

This review discusses female androgenetic alopecia, highlighting its diagnostic challenges and management strategies, but it reports no new results.

This review discusses the physiopathology of androgenetic alopecia and evaluates various traditional and emerging treatments, reporting no new clinical results but highlighting the need for enhanced treatment strategies.

This study developed a method for generating germ-like tissues called bbHFGs, which efficiently promoted hair follicle formation in mice, potentially advancing hair regenerative medicine applications.

This review discusses methods for evaluating hair growth-promoting effects of candidate substances for androgenetic alopecia, focusing on cell assays, organ cultures, and animal models, and reports no new results.

In this multicenter study, androgenetic alopecia was the most common type of alopecia among both men and women attending specialty hair clinics on four continents.

The authors concluded that dermal white adipose tissue, influenced by factors like light irradiation, plays a significant role in modulating hair follicle cycles and could be targeted for hair growth treatments.

This study demonstrated that enhancing human skin constructs with hair follicles through engineered cell organization and vascularization improved hair growth in immunodeficient mice, suggesting potential advances for treating alopecia and chronic wounds.

This review discusses the use of Dermal Papilla cells as in vitro models for studying hair growth modulators, emphasizing their role in aiding the development of new hair treatments, but reports no new clinical results.

This study found that DECORIN promotes the proliferation and migration of outer root sheath keratinocytes in vitro and maintains the hair anagen phase in mice.

This study found that autophagy plays a novel role in human hair growth, with altered autophagic flux during hair development phases influencing hair follicle behavior in a preclinical model.

In this study, researchers successfully derived skin organoids from mouse pluripotent stem cells that spontaneously produce hair follicles, potentially aiding in hair growth research and in vitro drug testing.

This study observed that nicotinamide can effectively inhibit human hair growth and promote hair follicle regression in cultured human scalp models without negatively affecting epidermal vitality, suggesting its potential as a hair growth inhibitor in cosmetic applications.

This review discusses the role of Hedgehog signaling in epidermal and hair follicle development and its involvement in basal cell carcinoma, without reporting new empirical findings.

The study found that finasteride increased endoplasmic reticulum stress and reduced fertility in rats, effects that were alleviated by the administration of DA-9401.

This study found that newborn mouse skin organoids can robustly grow hair in vivo, while adult organoids require specific interventions to restore their hair-forming ability.

In this study, researchers differentiated induced pluripotent stem cells into cells with dermal papilla-like properties, demonstrating their potential role in hair follicle bioengineering and drug testing for hair growth.

This study found that in Japanese male patients with androgenetic alopecia, dutasteride 0.5 mg daily over 52 weeks was associated with improvements in hair growth and appearance, with reported adverse events mostly mild.

This study found that 3D microtissue models of dermal papilla cells can enhance the ability to induce hair-follicle neogenesis in vivo, offering potential for controlled cell production in follicle regeneration.

This study found that dutasteride 0.5 mg was generally well-tolerated and led to overall improvement in male patients aged 18 to 41 with androgenic alopecia in a Korean clinical practice setting.

This article presents a comprehensive guide for classifying human hair follicle cycle stages in vivo using scalp xenografts on immunocompromised mice, offering valuable resources for researchers in the field.

This review provides a comprehensive guide to serum-free human hair follicle organ culture methods, highlighting research opportunities, standardization efforts, and potential applications without reporting new empirical findings.

This study found that expanding hair follicle keratinocytes with a fibroblast feeder followed by short-term coculture with dermal papilla cells could restore their ability to form new hair follicles.

This study found that macrophages near hair follicles contribute to the activation of skin epithelial stem cells in mice, suggesting a novel role for macrophages in regulating hair growth.

This article provides contact information for Bruce A. Morgan and features no new research findings.

This study reported that sulfotransferase activity in plucked hair follicles can predict treatment response to 5% topical minoxidil in women with androgenetic alopecia with high sensitivity and specificity.

This article reviews the complex signaling pathways between epithelial and mesenchymal cells crucial for hair follicle morphogenesis, highlighting the Wnt pathway's role as a master regulator without reporting new experimental findings.

This study found that altering cell culture conditions to form three-dimensional papilla spheroids can restore the ability of human dermal papilla cells to induce hair growth in adult skin.

In this study, oral administration of Crataegus pinnatifida extract was associated with hair growth promotion in mice by inducing anagen phase and enhancing cell signaling related to hair follicle development.

This review discusses mesenchymal–epithelial interactions in hair follicle development and cycling, highlighting recent insights without reporting new experimental results.

This review describes minoxidil's hair regrowth mechanism and discusses dermatological applications, but reports no new clinical results, emphasizing the need for regular use and addressing allergic reactions.

In this mouse study, researchers found that dermal Wnt signaling/β-catenin activity is essential for fibroblast proliferation and initiating hair follicle formation by interacting with epidermal Wnt ligands.

In this study, IGF-I was shown to enhance human hair follicle growth, maintain the anagen phase, and increase expression of certain growth factors and anti-apoptotic markers.

This study found that in a population of hair follicles, regenerative cycling stages are regulated by both intrinsic and extrinsic signals, with WNT/BMP signaling mediating interactions among follicles for adaptability.

This study found that topical minoxidil modestly extended the anagen phase in mice by activating β-catenin activity in dermal papilla cells.

This study found that increased expression of type II 5α-reductase, androgen receptors, and Hic-5/ARA55 in dermal papilla cells upregulates androgen sensitivity, playing a key role in androgenetic alopecia pathogenesis.

This study found that 0.5 mg of dutasteride significantly improved hair growth compared to placebo and was well tolerated over six months in men with male pattern hair loss.

This study found that in mice, inactivating beta-catenin in the dermal papilla reduces hair follicle progenitor proliferation and disrupts the hair cycle.

This study reports the development of the first rodent model for androgenetic alopecia, demonstrating that overexpression of androgen receptors in mice delays hair regeneration and can be used to test new treatments.

Hair transplantation is a treatment for hair loss mainly caused by genetics, with various techniques and potential complications, and results visible after 8-12 months.

This study introduced a new classification system for distinguishing between anagen VI and early catagen stages in human hair follicle organ culture, using it to confirm eflornithine's ability to induce premature catagen.

This review discusses the development and advances in studying trichogenic dermal cells for hair follicle morphogenesis, summarizing methods, bioassays, and molecular markers, but reports no new research findings.

This study found that Minoxidil had biphasic effects on normal human keratinocytes, stimulating proliferation at micromolar doses, but showing antiproliferative, pro-differentiative, and cytotoxic effects at millimolar concentrations.

This study explored the interaction between androgen and Wnt signaling in dermal papilla cells, targeting the effects of androgen on hair growth reduction.

This research discusses how epithelial stem cells in the skin maintain normal homeostasis, contribute to wound repair, and highlights the importance of these processes, as defects can lead to skin diseases including cancers, but provides no new experimental results.

This study found that human hair follicles express ATP-sensitive potassium channels, suggesting that minoxidil acts on these channels and that drugs targeting them may treat hair disorders.

This review discusses the hierarchical structure and chemical properties of hair fibers and offers insights for chemists and biochemists, but reports no new experimental findings.

This article reviews the stages and regulation of the hair cycle, highlighting molecular regulators involved, but it does not present new research findings.

This study found that minoxidil stimulates hair follicle growth by promoting dermal papilla cell survival and activating ERK and Akt pathways, which leads to increased proliferation and reduced cell death.

This study reports that the prevalence of male pattern baldness in Asians is higher than previously believed, with potential links to socioeconomic factors and westernized diets, though the exact cause remains unclear.

This study found that 5% topical minoxidil significantly increased hair regrowth and improved psychosocial perceptions of hair loss in men with androgenetic alopecia compared to 2% topical minoxidil and placebo over 48 weeks.

This review summarizes recent advances in understanding the molecular mechanisms of hair follicle formation and discusses potential future clinical applications for treating hair loss and skin tumors, but it reports no new clinical results.

In this study, the prevalence of androgenetic alopecia among Korean men and women was found to be lower than in caucasians, with Korean men showing more frontal hairline preservation and a higher incidence of 'female pattern' hair thinning.

This study found that using a novel dissolving microneedle with valproic acid effectively enhances hair follicle regrowth through improved delivery and activation of the Wnt/β-catenin pathway compared to topical application.

This study found that topical estradiol inhibits hair growth in mice by preventing the hair follicle's transition from resting to growth phase, a process reversible with an estrogen receptor antagonist.

In male pattern hair loss, this study found that finasteride 1 mg daily significantly slowed hair loss and increased hair growth over two years compared to placebo.

This study found that minoxidil significantly increases VEGF mRNA and protein expression in dermal papilla cells, suggesting a role in enhancing hair follicle vascularization in androgenetic alopecia.

This study found that a non-scarring alopecia in C3H/HeJ mice resembles human alopecia areata and may serve as a valuable model for studying specific subtypes of the human condition.

In this study, isolated human hair follicles maintained prolonged growth and consistent DNA and keratin synthesis patterns in a fully defined medium for at least 9 days while preserving in vivo-like morphology.