OBJECTIVE: To review recent advances in the application of hair transplantation in wound healing and scar repair in special areas. METHODS: An extensive review of the literature on the application of hair transplantation in wound healing and scar repair in special areas was conducted, focusing on cellular functions, molecular mechanisms, and clinical applications. RESULTS: Hair transplantation has been shown to effectively promote wound healing and scar repair in special areas. The underlying mechanisms are complex, but current understanding emphasizes a strong association with hair follicle-associated stem cells (including epidermal stem cells, dermal papilla cells, dermal sheath cells, etc). CONCLUSION The application of hair transplantation in wound healing and scar repair in special areas remains in its early stages. Further investigation into its mechanisms of action is essential, and randomized controlled trials are needed to establish its efficacy.
Humans ; Wound Healing/physiology* ; Cicatrix/therapy* ; Hair/transplantation* ; Hair Follicle/transplantation*

OBJECTIVE: To determine the expression level of Sonic hedgehog (Shh) in the passage of hair follicle stem cells (HFSCs), analyze the effect of Shh overexpression on the proliferation activity of HFSCs, and explore the survival of HFSCs after Shh overexpression and its effect on hair follicle regeneration. METHODS: Hair follicles from the normal area (H1 group) and alopecia area (H2 group) of the scalp donated by 20 female alopecia patients aged 40-50 years old were taken, and the middle part of the hair follicle was cut under the microscope to culture, and the primary HFSCs were obtained and passaged; the positive markers (CD29, CD71) and negative marker (CD34) on the surface of the fourth generation HFSCs were identified by flow cytometry. The two groups of HFSCs were transfected with Shh-overexpressed lentivirus. Flow cytometry and cell counting kit 8 assay were used to detect the cell cycle changes and cell proliferation of HFSCs before and after transfection, respectively. Then the HFSCs transfected with Shh lentivirus were transplanted subcutaneously into the back of nude mice as the experimental group, and the same amount of saline was injected as the control group. At 5 weeks after cell transplantation, the expression of Shh protein in the back skin tissue of nude mice was detected by Western blot. HE staining and immunofluorescence staining were used to compare the number of hair follicles and the survival of HFSCs between groups. RESULTS: The isolated and cultured cells were fusiform and firmly attached to the wall; flow cytometry showed that CD29 and CD71 were highly expressed on the surface of the cells, while CD34 was lowly expressed, suggesting that the cultured cells were HFSCs. The results of real-time fluorescence quantitative PCR and Western blot showed that the expression levels of Shh protein and gene in the 4th, 7th, and 10th passages of cells in H1 and H2 groups decreased gradually with the prolongation of culture time in vitro. After overexpression of Shh, the proliferation activity of HFSCs in the two groups was significantly higher than that in the blank group (not transfected with lentivirus) and the negative control group (transfected with negative control lentivirus), and the proliferation activity of HFSCs in H1 group was significantly higher than that in H2 group before and after transfection, showing significant differences ( P<0.05). At 5 weeks after cell transplantation, Shh protein was stably expressed in the dorsal skin of each experimental group; the number of hair follicles and the expression levels of HFSCs markers (CD71, cytokeratin 15) in each experimental group were significantly higher than those in the control group, and the number of hair follicles and the expression levels of HFSCs markers in H1 group were significantly higher than those in H2 group, and the differences were significant ( P<0.05). CONCLUSION Lentivirus-mediated Shh can be successfully transfected into HFSCs, the proliferation activity of HFSCs significantly increase after overexpression of Shh, which can secrete and express Shh continuously and stably, and promote hair follicle regeneration by combining the advantages of stem cells and Shh.
Animals ; Female ; Mice ; Alopecia/surgery* ; Hair Follicle ; Hedgehog Proteins/genetics* ; Mice, Nude ; Regeneration ; Stem Cells

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

BACKGROUND: Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits. METHODS: First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo . Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate. RESULTS: Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P  < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation. CONCLUSIONS hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.
Animals ; Humans ; Rabbits ; Hair Follicle ; Achilles Tendon/pathology* ; Tendinopathy/pathology* ; Proteomics ; Collagen Type I ; Mesenchymal Stem Cells

Objective: To explore the clinical effects of autologous follicular unit extraction (FUE) transplantation in the treatment of small area secondary cicatricial alopecia (hereinafter referred to as cicatricial alopecia) after burns. Methods: A retrospective observational study was carried out. According to the adopted treatment methods, 18 patients (12 males and 6 females, aged (29±6) years) who received autologous FUE transplantation for small area cicatricial alopecia after burns from March 2017 to November 2019 in the First Affiliated Hospital of Air Force Medical University were included in FUE transplantation group, and 18 patients (13 males and 5 females, aged (33±5) years) who were treated with expanded flap transplantation for small area cicatricial alopecia after burns by the same surgery team during the same period in the same hospital were included in expanded flap transplantation group. All the patients were followed up for more than 1 year. At the last follow-up, the follicular unit density in the transplanted area was measured by Folliscope hair detection system and the hair survival rate was calculated; the visual analogue scale (VAS) method was adopted to evaluate the treatment effect; patients were asked their satisfaction with the treatment effect and the occurrence of complications during follow-up; the hair growth and the scalp thickness, pain, pruritus, pigmentation, and surface roughness of the transplanted area were recorded. Data were statistically analyzed with Fisher's exact probability test and independent sample t test. Results: At the last follow-up, the follicular unit density in the transplanted area of patients in FUE transplantation group was (46.8±2.0)/cm², which was significantly higher than (42.5±4.3)/cm² in expanded flap transplantation group (t=3.84, P<0.01); the hair survival rates of patients were similar between the two groups (P>0.05). At the last follow-up, VAS scores evaluating the treatment effect of patients were similar between the two groups (P>0.05); the satisfaction score of patients toward the treatment effect in FUE transplantation group was 8.6±1.1, which was significantly higher than 7.6±0.8 in expanded flap transplantation group (t=2.89, P<0.01). During the follow-up, no inflammation or infection occurred in patients of the two groups, but only 2 patients in expanded flap transplantation group had postoperative pain. At the last follow-up, the transplanted area of patients in the two groups was covered with new hair, and the hair growth direction was basically consistent with the surrounding normal hair; scalp thickness, pain, pruritus, pigmentation, and surface roughness of the transplanted area of patients were similar between the two groups (P>0.05). Conclusions: Autologous FUE transplantation has better long-term follicular unit density and patients' satisfaction than expanded flap transplantation in the treatment of small area cicatricial alopecia after burns, showing better postoperative effect and a good prospect of clinical application.
Alopecia/surgery* ; Burns/surgery* ; Cicatrix/surgery* ; Female ; Hair Follicle ; Humans ; Male ; Pain/complications* ; Pruritus/complications*

Humans ; Finasteride/pharmacology* ; Dutasteride/pharmacology* ; 5-alpha Reductase Inhibitors/pharmacology* ; Testosterone/metabolism* ; Hair Follicle/metabolism* ; Transcriptome ; Hair/metabolism*

There is growing evidence that dermal papilla cells(DPCs)act as the organizing center to induce the cyclic hair regeneration.On one hand,DPCs secrete cytokines or growth factors to regulate the differentiation,proliferation,and migration of epithelial stem cells(EpSCs)and melanocyte stem cells(MeSCs)residing in the bulge region.On the other hand,DPCs manipulate the microenvironment(also termed as niche)for both EpSCs and MeSCs,such as the size of dermal papilla,the distance between dermal papilla and the bulge region,and the lymphatic drainage and sympathetic nerve innervation surrounding the bulge region,thereby orchestrating the cycling hair growth.Recent studies have demonstrated at least four subpopulations existing in dermal papillae,which induce the unilineage transit-amplifying epithelial cells to form the concentric multilayers of hair shafts and sheaths.In addition,emerging study has indicated that sustained psychological stress potentially leads to hyperactivation of the sympathetic nerves that innervate the bulge region.The large amount of norepinephrine released by the nerve endings forces MeSCs to rapidly and abnormally proliferate,resultantly causing the depletion of MeSC pool and the loss of hair pigment.Understanding the molecular regulation of hair growth and pigmentation by DPCs holds substantial promise for the future use of cultured DPCs
Cell Differentiation ; Cells, Cultured ; Dermis ; Hair Follicle ; Pigmentation

hair loss based on the Hamilton–Norwood classification and women with stage I to III patterns of hair loss based on the Ludwig classification. All patients were administered 80 mL of Mogut® (a kimchi and cheonggukjang probiotic product) twice a day. Hair growth and numbers were measured using the Triple Scope System® (KC Technology, Korea) at baseline and after 1 and 4 months of administration of a kimchi and cheonggukjang probiotic product.RESULTS: At baseline, the mean hair count was 85.98±20.54 hairs/cm2 and the mean thickness was 0.062±0.011 mm in all patients (n=46). Hair count and thickness had significantly increased at 1 month (90.28±16.13 hairs/cm2 and 0.068±0.008 mm, respectively) and at 4 months (91.54±16.29 hairs/cm2 and 0.066±0.009 mm, respectively). In this study, we found that a kimchi and cheonggukjang probiotic product could promote hair growth and reverse hair loss without associated adverse effects such as diarrhea.CONCLUSIONS: We suggest that the observed improvements in hair count and thickness resulted from initiation of the anagen phase in hair follicles in response to probiotics.]]>
Alopecia ; Classification ; Diarrhea ; Female ; Functional Food ; Hair ; Hair Follicle ; Humans ; Leuconostoc ; Male ; Pilot Projects ; Probiotics ; Scalp ; Soybeans

Anagen effluvium is an abrupt loss of hair in its growing phase due to an event that impairs the mitotic or metabolic activity of the hair follicle. Anagen effluvium is commonly associated with the administration of chemotherapy, radiation, and drugs as well as exposure to toxic chemicals. However, alopecia due to the administration of anti-tuberculosis drugs has rarely been reported in the literature. A 50-year-old female was diagnosed with intestinal tuberculosis and was started on anti-tuberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide. After starting the treatment, erythematous to brown patches appeared all over her body, which was followed by diffuse hair loss on the scalp and body. Hair examination showed intact inner and outer root sheaths with fully pigmented hair bulbs, and histopathological examination of a scalp biopsy showed vacuolar degeneration in the interfollicular epidermis and perifollicular infiltration of mononuclear cells and eosinophils. The condition was diagnosed as anagen effluvium with drug eruption, and a potent corticosteroid lotion was prescribed for scalp application twice a day. After complete hair loss, the anti-tuberculosis medications were withdrawn, and hair regrowth started 4 months later. Here, we report a rare case of anagen effluvium with generalized drug eruption due to anti-tuberculosis medication.
Alopecia ; Biopsy ; Drug Eruptions* ; Drug Therapy ; Eosinophils ; Epidermis ; Ethambutol ; Female ; Hair ; Hair Follicle ; Humans ; Isoniazid ; Middle Aged ; Pyrazinamide ; Rifampin ; Scalp ; Tuberculosis

BACKGROUND: AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays a pivotal role in the balance of cellular energy metabolism. Recent studies have reported that AMPK has numerous roles in physiological conditions, and dysregulation of AMPK induces pathological processes and diseases. However, the role of AMPK and its activators have not yet been studied in the context of hair growth regulation. OBJECTIVE: To investigate the effects of metformin on dermal papilla (DP) and outer root sheath (ORS) cells, as well as the role of the AMPK pathway in hair growth. METHODS: We evaluated whether metformin, a well-known AMPK activator, had any beneficial effects on hair growth. In addition, to evaluate the molecular and cellular mechanisms that were involved, protein levels of AMPK and β-catenin were analyzed. RESULTS: Metformin increased the cellular proliferation of human DP and ORS cells. Ki-67 expression was also significantly increased after metformin treatment in the ex vivo hair follicle organ culture. Furthermore, DP and ORS cells treated with metformin had a significant increase in AMPK phosphorylation, which in turn suppressed β-catenin degradation and enhanced its nuclear accumulation. CONCLUSION: We demonstrated that metformin promoted hair growth via the AMPK/β-catenin signaling pathway in vitro with DP and ORS cells. The hair-promoting effects of AMPK activators may potentially be used for the treatment of alopecia, and further investigation will be needed in the future.
Alopecia ; AMP-Activated Protein Kinases ; beta Catenin ; Cell Proliferation ; Energy Metabolism ; Hair Follicle ; Hair ; Humans ; In Vitro Techniques ; Metformin ; Organ Culture Techniques ; Pathologic Processes ; Phosphorylation ; Protein Kinases