Embryonic-Like Regenerative Phenomenon: Wound-Induced Hair Follicle Neogenesis

September 2018 in “ Regenerative Medicine ”

Lin Gong, Xue-Gang Xu, Yuan-Hong Li

Studysummary This review explores the mechanism and potential applications of wound-induced hair follicle neogenesis but reports no new clinical results, highlighting the need for further research in hair regeneration therapies.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The document from September 1, 2018, reviews the process of wound-induced hair follicle neogenesis (WIHN), where new hair follicles form in the center of a full-thickness wound in adult mice, similar to embryonic hair development. It was found that a sufficiently large wound is required for WIHN to occur, with new follicles forming between days 14-21 post-wound, and the number of new follicles decreases with the age of the mice. The cellular origins of WIHN are not from hair stem cells in the bulge but may involve reprogramming of epidermal and upper follicle cells. Key molecular mechanisms include the Wnt/ß-catenin pathway, with Wnt ligands from epidermal cells activating ß-catenin in the dermis, and FGF9, secreted by γδ T cells, also playing a regulatory role. The findings suggest that understanding WIHN could lead to new treatments for hair loss and contribute to regenerative medicine and stem cell research.

View this study on futuremedicine.com →

Discuss this study in the Community →

Research cited in this study

38 / 38 results

research Wound Regeneration Deficit in Rats Correlates with Low Morphogenetic Potential and Distinct Transcriptome Profile of Epidermis

21 citations , January 2018 in “Journal of Investigative Dermatology”

This study found that large excisional wounds in rats across seven strains do not regenerate new hair follicles, unlike in mice, possibly due to differences in epidermal competence and transcriptional profiles.

research Dermal Blimp1 Acts Downstream of Epidermal TGFβ and Wnt/β-Catenin to Regulate Hair Follicle Formation and Growth

85 citations , June 2017 in “Journal of Investigative Dermatology”

This study found that Blimp1 plays a key role in promoting hair follicle morphogenesis and growth by mediating inductive signaling pathways in dermal papilla cells.

research Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis

37 citations , June 2017 in “Journal of Investigative Dermatology”

This study suggests that the interaction between CXXC5 and Dishevelled is a potential target for promoting hair regrowth and hair follicle formation, offering a new approach to treat hair loss.

research Macrophages Induce AKT/β-Catenin-Dependent Lgr5+ Stem Cell Activation and Hair Follicle Regeneration Through TNF

117 citations , March 2017 in “Nature Communications”

This study shows that macrophage-induced TNF signaling can activate hair follicle stem cells and promote new hair follicle formation after wounding by regulating AKT/β-catenin pathways.

Double-Stranded RNA Induces Inflammation via the NF-κB Pathway and Inflammasome Activation in the Outer Root Sheath Cells of Hair Follicles

research Double-Stranded RNA Induces Inflammation via the NF-κB Pathway and Inflammasome Activation in the Outer Root Sheath Cells of Hair Follicles

22 citations , March 2017 in “Scientific reports”

This study investigated the role of NLRP3 inflammasomes in alopecia areata and found that outer root sheath cells may contribute to inflammation by increasing IL-1β and HMGB1 secretion when stimulated with double-stranded RNA.

research Msi2 Maintains Quiescent State of Hair Follicle Stem Cells by Directly Repressing the Hedgehog Signaling Pathway

29 citations , January 2017 in “Journal of Investigative Dermatology”

This study found that increased MSI2 expression in hair follicle stem cells can delay hair growth by maintaining stem cell quiescence and repressing Hedgehog signaling.

research Regeneration of Fat Cells from Myofibroblasts During Wound Healing

408 citations , January 2017 in “Science”

This study found that hair follicles in mice and humans can convert wound-related myofibroblasts into adipocytes, suggesting a potential pathway to reduce scar formation by activating BMP signaling.

research Interleukin-6 Null Mice Paradoxically Display Increased STAT3 Activity and Wound-Induced Hair Neogenesis

16 citations , January 2016 in “Journal of Investigative Dermatology”

This study found that IL-6 knockout mice exhibited increased wound-induced hair neogenesis compared to wild-type mice, likely due to enhanced STAT3 activation facilitated by compensatory cytokine activity.

research Interleukin 6 and STAT3 Regulate p63 Isoform Expression in Keratinocytes During Regeneration

11 citations , November 2015 in “Experimental Dermatology”

This study reported that IL-6/STAT3 signaling influences p63 isoform expression in keratinocytes and is involved in wound-induced hair follicle neogenesis, highlighting the interplay between immune and developmental pathways.

research dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration

128 citations , August 2015 in “Cell Stem Cell”

The researchers reported that dsRNA from damaged skin activates TLR3, promoting hair follicle regeneration, while TLR3-deficient animals fail to initiate this process, suggesting potential therapeutic approaches for hair neogenesis.

research Intravital Imaging of Hair Follicle Regeneration in the Mouse

56 citations , June 2015 in “Nature Protocols”

This protocol describes using two-photon laser-scanning microscopy to study hair regeneration in live mice, offering detailed imaging capabilities for observing hair follicle stem cell behavior and manipulating cellular populations.

research Macrophages Contribute to the Cyclic Activation of Adult Hair Follicle Stem Cells

175 citations , December 2014 in “PLoS Biology”

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.

research Epigenetic Control of Skin and Hair Regeneration After Wounding

36 citations , July 2014 in “Experimental Dermatology”

This narrative piece considers how epigenetic factors may influence the processes of skin wound healing, including hair follicle formation, but it presents no new experimental results.

research At the Dawn of Hair Research – Testing the Limits of Hair Follicle Regeneration

6 citations , February 2014 in “Experimental Dermatology”

This review discusses the potential for cellular hair regeneration by building on foundational rodent studies and emphasizes the need for protocols to enhance the inductive properties of human dermal papilla cells.

research Stem Cell Dynamics in the Hair Follicle Niche

135 citations , December 2013 in “Seminars in Cell & Developmental Biology”

This review examines the literature on the molecular and cellular makeup of the hair follicle niche and how it influences stem cell behavior during hair regeneration, but does not provide new experimental results.

research Distinct Fibroblast Lineages Determine Dermal Architecture in Skin Development and Repair

1235 citations , December 2013 in “Nature”

This study found that skin fibroblasts in mice arise from two distinct lineages which contribute differently to dermal structure and repair, impacting hair follicle formation during wound healing.

research Fgf9 From Dermal γδ T Cells Induces Hair Follicle Neogenesis After Wounding

237 citations , June 2013 in “Nature Medicine”

This study found that fibroblast growth factor 9, initially secreted by γδ T cells, plays a key role in modulating hair follicle regeneration in mice after skin wounds.

research Prostaglandin D2 Inhibits Wound-Induced Hair Follicle Neogenesis Through the Receptor Gpr44

68 citations , November 2012 in “Journal of Investigative Dermatology”

This study found that PGD2 inhibits hair follicle regeneration in mice through the Gpr44 receptor, suggesting that blocking PGD2 or Gpr44 may enhance skin regeneration after wounds.

research Skin Shedding and Tissue Regeneration in African Spiny Mice (Acomys)

418 citations , September 2012 in “Nature”

This study reports the first instance of skin autotomy in mammals, specifically in African spiny mice, and suggests they may possess a greater regenerative capacity than previously understood, possibly offering insights for regenerative medicine.

research Epithelial Wnt Ligand Secretion Is Required for Adult Hair Follicle Growth and Regeneration

170 citations , July 2012 in “Journal of Investigative Dermatology”

In this study, researchers showed that Wnt ligands secreted by hair follicle epithelium are crucial for hair follicle regeneration and may be significant for treating hair disorders like alopecia.

research Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia

205 citations , March 2012 in “Science Translational Medicine”

PGD2 stops hair growth and is higher in bald men with AGA.

Dermal β-Catenin Activity in Response to Epidermal Wnt Ligands Is Required for Fibroblast Proliferation and Hair Follicle Initiation

research Dermal β-Catenin Activity in Response to Epidermal Wnt Ligands Is Required for Fibroblast Proliferation and Hair Follicle Initiation

207 citations , March 2012 in “Development”

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.

research Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicles in Mice

173 citations , September 2011 in “Journal of Investigative Dermatology”

IL-6 contributes to hair loss by shortening the growth phase and causing hair follicles to regress.

research Nerve-Derived Sonic Hedgehog Defines a Niche for Hair Follicle Stem Cells Capable of Becoming Epidermal Stem Cells

396 citations , May 2011 in “Cell stem cell”

This study found that Shh from neurons signals to Gli1-expressing cells in the hair follicle, cultivating a niche where these bulge cells can potentially transform into epidermal stem cells in wound healing.

research Characterization and Quantification of Wound-Induced Hair Follicle Neogenesis Using In Vivo Confocal Scanning Laser Microscopy

26 citations , April 2011 in “Skin Research and Technology”

This study found that in vivo confocal scanning laser microscopy accurately quantifies neogenic hair follicles in mice, producing results similar to histology while avoiding fixation artifacts.

research Hair Follicle Neogenesis Induced by Cultured Human Scalp Dermal Papilla Cells

63 citations , September 2009 in “Regenerative Medicine”

This study developed a method for expanding human dermal papilla cells in vitro while maintaining their ability to induce hair growth, advancing the potential for follicular cell implantation as a treatment for hair loss.

research Lrig1 Expression Defines a Distinct Multipotent Stem Cell Population in Mammalian Epidermis

503 citations , May 2009 in “Cell stem cell”

This study suggests that Lrig1-positive cells form a previously unknown reservoir of interfollicular epidermal stem cells in adult mouse skin, influencing epidermal proliferation and hair follicle development.

research The Hair Follicle as a Dynamic Mini-Organ

759 citations , February 2009 in “Current Biology”

This review summarizes fundamental concepts and recent advancements in hair follicle biology, including insights from mouse models into broader molecular and cellular processes relevant to regeneration and development.

research Lgr5 Marks Cycling, Yet Long-Lived, Hair Follicle Stem Cells

835 citations , October 2008 in “Nature Genetics”

Lgr5 is a marker for active, long-lasting stem cells in mouse hair follicles.

research Nfatc1 Balances Quiescence and Proliferation of Skin Stem Cells

415 citations , January 2008 in “Cell”

NFATc1 controls hair stem cell activity, affecting hair growth and could be a target for hair loss treatments.

research Wnt-Dependent De Novo Hair Follicle Regeneration in Adult Mouse Skin After Wounding

829 citations , May 2007 in “Nature”

Hair follicles can regrow in wounded adult mouse skin using a process like embryo development.

research Modulation of Hair Growth with Small Molecule Agonists of the Hedgehog Signaling Pathway

113 citations , September 2005 in “Journal of Investigative Dermatology”

This study found that a topical hedgehog agonist can stimulate hair growth by promoting the transition from the resting to growth phase of the hair cycle in adult mouse skin.

research Influence of Prostaglandin F2α and Its Analogues on Hair Regrowth and Follicular Melanogenesis in a Murine Model

103 citations , April 2005 in “Experimental dermatology”

This study found that PGF2alpha analogues and PGE2 stimulated hair follicle activity in mice, with PGF2alpha analogues also linked to potential side effects like poliosis when used as eye treatments.

research Keratin 15 Promoter Targets Putative Epithelial Stem Cells in the Hair Follicle Bulge

387 citations , November 2003 in “Journal of Investigative Dermatology”

The K15 promoter effectively targets stem cells in the hair follicle bulge.

research Enrichment for Living Murine Keratinocytes from the Hair Follicle Bulge with the Cell Surface Marker CD34

561 citations , April 2003 in “Journal of Investigative Dermatology”

CD34 is a marker for isolating stem-like cells in mouse hair follicles.

research Tcf3 and Lef1 Regulate Lineage Differentiation of Multipotent Stem Cells in Skin

555 citations , July 2001 in “Genes & Development”

This study found that Tcf3 and Lef1 differently regulate cell differentiation in multipotent skin stem cells, with Tcf3 promoting follicle-like features and Lef1, when modified, promoting sebocyte differentiation.

research Onset of Keratin 17 Expression Coincides with the Definition of Major Epithelial Lineages During Skin Development

318 citations , October 1998 in “The Journal of Cell Biology”

This study found that ectopic expression of the lymphoid-enhancer factor can induce K17 protein in the skin, suggesting a link between skin development and wound repair processes in mice.

research The Formation of Vellus Hair Follicles from Human Adult Epidermis

73 citations , July 1956 in “Journal of Investigative Dermatology”

This paper provides evidence supporting the formation of new hair follicles in adult humans, building on findings previously demonstrated in rabbits.