Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies

With alopecia affecting millions globally, recent advancements in the understanding of hair follicle biology have driven the development of novel therapies focused on hair regrowth. This review discusses two emerging therapeutic strategies: hair follicle neogenesis and the modulation of the Wnt/B-ca...

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Main Authors: Apoorva Mehta, Mateen Motavaf, Danyal Raza, Alison J. McLure, Kofi D. Osei-Opare, Lindsey A. Bordone, Alejandro A. Gru
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/11/779
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author Apoorva Mehta
Mateen Motavaf
Danyal Raza
Alison J. McLure
Kofi D. Osei-Opare
Lindsey A. Bordone
Alejandro A. Gru
author_facet Apoorva Mehta
Mateen Motavaf
Danyal Raza
Alison J. McLure
Kofi D. Osei-Opare
Lindsey A. Bordone
Alejandro A. Gru
author_sort Apoorva Mehta
collection DOAJ
description With alopecia affecting millions globally, recent advancements in the understanding of hair follicle biology have driven the development of novel therapies focused on hair regrowth. This review discusses two emerging therapeutic strategies: hair follicle neogenesis and the modulation of the Wnt/B-catenin signaling pathway. Hair follicle neogenesis, a frontier once considered impossible to achieve in adult humans, has recently gained traction due to advancements in stem cell biology and further understanding of the epithelial–mesenchymal interactions that are critical to hair follicle development. Such an approach shows significant potential for addressing conditions leading to hair loss, such as androgenetic and scarring alopecias. The Wnt/B-catenin signaling pathway, a critical intracellular pathway responsible for hair follicle cycles, has gained traction as a target for therapeutic interventions. Studies show that stimulating this pathway leads to hair follicle growth, while its inhibition prompts hair follicle regression. Investigations demonstrate clinical efficacy of small molecule inhibitors and peptides, such as PTD-DBM, which activates the Wnt/β-catenin pathway by interfering with CXXC5, a negative regulator that inhibits pathway activation. Such therapies show potential as more effective treatment options than existing solutions such as finasteride and minoxidil. Adjunctive therapies, such as low-level laser therapy, have also shown clinical efficacy, further highlighting how modulation of this pathway stimulates follicular regrowth. While these novel therapies require further research to validate their efficacy and to gain additional insight into their risk profile, it is clear that alopecia treatment is approaching a new frontier beyond traditional pharmacologic interviews, with regenerative medicine and pathway modulation paving the way forward.
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spelling doaj-art-5c8e7dc2c9b44f4fa837b7024e6fd2172025-08-20T03:46:48ZengMDPI AGCells2073-44092025-05-01141177910.3390/cells14110779Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging TherapiesApoorva Mehta0Mateen Motavaf1Danyal Raza2Alison J. McLure3Kofi D. Osei-Opare4Lindsey A. Bordone5Alejandro A. Gru6Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADuke University School of Medicine, Durham, NC 27710, USADuke University School of Medicine, Durham, NC 27710, USAVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USAVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Dermatology, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Dermatology, Columbia University Irving Medical Center, New York, NY 10032, USAWith alopecia affecting millions globally, recent advancements in the understanding of hair follicle biology have driven the development of novel therapies focused on hair regrowth. This review discusses two emerging therapeutic strategies: hair follicle neogenesis and the modulation of the Wnt/B-catenin signaling pathway. Hair follicle neogenesis, a frontier once considered impossible to achieve in adult humans, has recently gained traction due to advancements in stem cell biology and further understanding of the epithelial–mesenchymal interactions that are critical to hair follicle development. Such an approach shows significant potential for addressing conditions leading to hair loss, such as androgenetic and scarring alopecias. The Wnt/B-catenin signaling pathway, a critical intracellular pathway responsible for hair follicle cycles, has gained traction as a target for therapeutic interventions. Studies show that stimulating this pathway leads to hair follicle growth, while its inhibition prompts hair follicle regression. Investigations demonstrate clinical efficacy of small molecule inhibitors and peptides, such as PTD-DBM, which activates the Wnt/β-catenin pathway by interfering with CXXC5, a negative regulator that inhibits pathway activation. Such therapies show potential as more effective treatment options than existing solutions such as finasteride and minoxidil. Adjunctive therapies, such as low-level laser therapy, have also shown clinical efficacy, further highlighting how modulation of this pathway stimulates follicular regrowth. While these novel therapies require further research to validate their efficacy and to gain additional insight into their risk profile, it is clear that alopecia treatment is approaching a new frontier beyond traditional pharmacologic interviews, with regenerative medicine and pathway modulation paving the way forward.https://www.mdpi.com/2073-4409/14/11/779follicle neogenesisB-Cateninhair regrowthhair therapiesalopeciaalopecia areata
spellingShingle Apoorva Mehta
Mateen Motavaf
Danyal Raza
Alison J. McLure
Kofi D. Osei-Opare
Lindsey A. Bordone
Alejandro A. Gru
Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies
Cells
follicle neogenesis
B-Catenin
hair regrowth
hair therapies
alopecia
alopecia areata
title Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies
title_full Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies
title_fullStr Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies
title_full_unstemmed Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies
title_short Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies
title_sort revolutionary approaches to hair regrowth follicle neogenesis wnt ss catenin signaling and emerging therapies
topic follicle neogenesis
B-Catenin
hair regrowth
hair therapies
alopecia
alopecia areata
url https://www.mdpi.com/2073-4409/14/11/779
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