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Alopecia is a common and distressing medical condition that has affected a majority of people worldwide, which leads to great effects on the quality of life and self-esteem. Numerous treatments had been used to cure alopecia, including hair growth stimulants, herbal products, and hair transplantation. However, these treatments have their side effects, such as hypertrichosis, edema, and even cardiovascular adverse effects, which lead to the urgent requirement to explore a new hair-follicle (HF) regeneration approach. Tissue engineering could be the potential way for HF regeneration by simulating the epithelial-mesenchymal interaction and cell-extracellular matrix interactions. This review summarized the potential cells that are used in tissue engineering, commonly used tissue engineering techniques, and most importantly, the biomaterials that have been applied for in vitro three-dimensional cell culture or in vivo co-transplantation in HF regeneration. The literature shows that advances in this field toward functional HF development have progressively increased. Although the clinical application of biomaterial co-transplantation for HF regeneration still faces various challenges, numerous studies have proved that this is a promising direction that could be achieved in the future.

Heat stress (HS) negatively affects the development of hair follicles. The present study investigated the effect of vitamin A (VA) on the development of rabbit dermal papilla cells (DPCs) under HS and the underlying regulatory mechanisms. Addition of 0.4 mg/L VA to the culture medium significantly enhanced cell proliferation (P

Introduction: Regenerative medicine is a promising approach for hair loss; however, its primary challenge is the inductivity of human dermal papilla cells (DPCs), which rapidly lose hair growth-inducing properties in 2D culture. Despite extensive research efforts to construct DPCs, current 3D microenvironments fabricated to restore hair inductivity remain insufficient. Objectives: Here, we aimed to fabricate ECM-enriched controllable vascularized dermal papilla (DP) spheroids that highly mimic in vivo DPCs microenvironments to restore their hair inductivity. Methods: We employed layer-by-layer (LbL) self-assembly using gelatin and alginate to construct nanoscale biomimetic ECM for DPCs, with Ca2+ as a cross-linking agent to create controllable DP spheroids. DPCs were also co-cultured with human umbilical vein endothelial cells to construct vascularized DP spheroids. Immunofluorescence staining and angiography was used to detect angiogenesis in vitro and in vivo. RNA sequencing and in vivo implantation were employed to investigate DPCs signature. Results: LbL technology enabled DPCs to aggregate into controllable DP spheroids of size and cell numbers similar to those of primary DP. Vascularization prevented hypoxia-induced necrosis and functioned in association with host vessels post-transplantation. Compared with traditional 3D culture, nanoscale ECM and vascularization were found to restore the transcriptional signature of DPCs and triple hair induction efficiency following engraftment. Conclusion: Our novel biomimetic developmental tissue engineering strategy is a crucial step toward the recovery of human DPC hair inductivity, which would enable the rapid clinical application of large-scale hair regeneration platforms.

Dermal papilla cells (DPCs) are crucial for the growth and development of hair follicles (HF). (-)-Epigallocatechin-3-gallate (EGCG) is the primary catechin identified in green tea, which has antioxidant effects and regulates cell activity. This study demonstrates that EGCG could promote the proliferation of DPCs. In addition, EGCG treatment significantly upregulated the expression of PCNA, CCND1, HIF-1α, VEGFA, and Bcl-2 mRNAs in DPCs, while significantly reducing the gene expression of Bax. The optimal concentration of EGCG addition was screened. When detecting the antioxidant ability of DPCs, treatment with 0.5 μM EGCG could intensify the relative activity of catalase, superoxide dismutase, and glutathione, promoting the antioxidant ability and migration of DPCs. Subsequently, the differentially expressed genes (DEGs) associated with the EGCG treatment in DPCs were identified by RNA sequencing, revealing 21 DEGs, including VEGFA, POSTN, CLU, SERPINE2, and NPY. As the candidate gene, the role of VEGFA in regulating HF growth and development was investigated. Immunofluorescence staining revealed that EGCG treatment enhanced the fluorescence intensity of VEGFA and CLU in DPCs. After VEGFA overexpression and knockdown in DPCs, it was found to regulate the HF growth and the expression of development-related genes, enhance the expression of proliferating cell nuclear antigen, and promote DPCs proliferation. EGCG could also rescue the siRNA-VEGFA effect in DPCs. Thus, this study demonstrates that EGCG possibly regulates cell viability in DPCs by inducing VEGFA expression level, and provides a reference for exploring the mechanism of HF growth and the treatment of hair-related illnesses., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2025. Published by Elsevier B.V.)

Decorin (DCN) is a member of the small leucine-rich proteoglycan family within the extracellular matrix, playing a role in the growth and development of hair follicle (HF). Exosomes serve as significant mediators of intercellular communication and are involved in the cyclic regeneration of HF. Exosomes derived from dermal papilla cells (DPC-Exos) are essential for the cycling and regrowth of HF. The present study demonstrated that DCN treatment significantly enhances the proliferation of DPCs, thereby promoting hair follicle growth. miRNA sequencing revealed 442 differentially expressed exosomal miRNAs. The regulatory mechanism of exosomal miR-129-2-3p, an up-regulated differential miRNA, was further investigated. The study identified its role in transporting DPCs to HFSCs through DPC-Exos. miR-129-2-3p has been shown to suppress the expression of genes associated with HF growth and development, lower the expression of genes and proteins downstream of the TGF-β signaling pathway, promote HFSC proliferation, and decrease HFSC apoptosis. Furthermore, miR-129-2-3p displayed an antagonistic effect on activating the TGF-β/SMAD3 signaling pathway induced by SRI-011381. The findings indicate that DCN-mediated DPC-Exos influence HF growth and development through the miR-129-2-3p/SMAD3/TGF-β regulatory axis. These results may facilitate novel strategies for the diagnosis and treatment of human hair disorders, in addition to enhancing industrial wool production., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Introduction: The dermal papilla (DP) represents the major regulatory entity within the hair follicle (HF), inducing hair formation and growth through reciprocal interactions with epithelial cells. However, human DP cells rapidly lose their hair inductive ability when cultured in an epithelium-deficient environment. Objectives: To determine if the conditioned medium collected from interfollicular keratinocytes (KCs-CM) is capable of improving DP cell native properties and inductive phenotype. Methods: DP cells were cultured with KCs-CM both in 2D and 3D culture conditions (spheroids). Further, the hair-inductive capacity of DP cells precultured with KCs-CM was tested in a hair reconstitution assay, after co-grafting with human keratinocytes in nude mice. Results: We demonstrate that KCs-CM contributes to restore the inductivity of cultured human DP cells in a more effective mode than the conventional 3D-cultures. This is supported by the higher active alkaline phosphatase (ALP) levels in DP cells, the improved self-aggregative capacity and the reduced expression of α-SMA and the V1-isoform of versican. Moreover, DP cells cultured with KCs-CM displayed a secretome profile (VEGF, BMP2, TGF- β1, IL-6) that matches the one observed during anagen. KCs-CM also enhanced DP cell proliferation, while preventing cells to undergo morphological changes characteristic of high passage cells. In opposition, the amount of collagenous and non-collagenous proteins deposited by DP cells was lower in the presence of KCs-CM. The improvement in ALP activity was maintained in 3D spheroidal cultures, even after KCs-CM retrieval, being superior to the effect of the gold-standard culture conditions. Moreover, DP cells cultured with KCs-CM and grafted with human keratinocytes supported the formation of HF- and sebaceous gland-like structures in mice. Conclusion: The proposed strategy encourages future cell-based strategies for HF regeneration not only in the context of hair-associated disorders, but also in the management of wounds to aid in restoring critical skin regulatory appendages.

Background: Long non-coding RNAs (lncRNAs), as post-transcriptional regulators, were thought to function in the inductive property of dermal papilla cells (DPCs) in cashmere goat. Previously, lncRNA-599554 was identified in secondary hair follicle (SHF) of cashmere goat, but its functional significance is unknown. Results: In the present investigation, we verified that lncRNA-599554 had significantly higher expression at the anagen dermal papilla of cashmere goat SHF than that at telogen. Based on overexpression and knockdown techniques, we found that lncRNA-599554 contributes the inductive property of DPCs of cashmere goat, which was assessed by detecting the changes in the expression of several typical indictor genes in DPCs including ET-1, SCF, Versican, ALP, Lef1 and Ptc-1. Based on RNA pull-down assay, we verified that lncRNA-599554 directly interacted with chi-miR-15a-5p. Also, we showed that lncRNA-599554 positively regulated the Wnt3a expression in DPCs but which did not appear to involve its modulating of promoter methylation. Based on the use of Dual-luciferase reporter assays, our data indicated that lncRNA-599554 regulated the Wnt3a expression through chi-miR-15a-5p-mediated post-transcriptional level. Conclusions: We showed that lncRNA-599554 contributes the inductive property of DPCs in cashmere goat which might be achieved through sponging chi-miR-15b-5p to promote the Wnt3a expression. The results from the present investigation provided a novel insight into the functional mechanism of lncRNA-599554 in the SHF regeneration of cashmere goat along with the formation and growth of cashmere fiber.How to cite: Yin RH, Wang YR, Zhao SJ, et al. LncRNA-599554 sponges miR-15a-5p to contribute inductive ability of dermal papilla cells through positive regulation of the expression of Wnt3a in cashmere goat. Electron J Biotechnol 2020;45. https://doi.org/10.1016/j.ejbt.2020.03.002

Background: MicroRNAs (miRNAs) are endogenous noncoding RNAs that regulate various biological processes. miR-125b is a miRNA that has been reported to be critical for hair follicle (HF) morphogenesis and development. We identified that the expression of miR-125b varies during an individual hair cycle (anagen, catagen, and telogen) in the skin of cashmere goats. We constructed a gain model (by overexpressing miR-125b) and a loss model (by inhibiting endogenous miR-125b) based on dermal papilla cells (DPCs) to further investigate the role of miR-125b in HF cycle. In addition, we used a dual-luciferase system to highlight the predicated target genes of miR-125b. Results: We found that miR-125b affects the expression of FGF5, IGF-1, SHH, TNF-α, MSX2, LEF-1, FGF7, NOGGIN, BMP2, BMP4, TGF-β1, and β-catenin. The dual-luciferase assay further validated a direct interaction between miR-125b and FGF5 and TNF-α. Conclusion: miR-125b affects the expression levels of genes related to hair cycle and may also play a critical role in regulating the periodic development of HF.

Aims: Hair follicles play a critical role in the process of hair growth. The dermal papilla cells (DPCs) are an important component in the hair follicle regeneration and growth. This study investigated the effects of ginsenoside Rb1 on the growth of cultured mink hair follicles and DPCs., Main Methods: The mink hair follicles were treated with ginsenoside Rb1 for 9 days and their lengths were measured every three days. Real-time PCR was used to determine the mRNA expression of vascularization endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGF-R2) and TGF-β1. In addition, the levels of proteins were detected by western blot. Cell proliferation was determined by immunofluorescence staining of proliferation marker Ki-67 and cell cycle analysis was performed on flow cytometry. Moreover, cell migration was evaluated by wound healing assay., Key Findings: Ginsenoside Rb1 promoted the growth of hair follicles, and proliferation and migration of DPCs. Ginsenoside Rb1 improved the expression levels of VEGFA and VEGF-R2, while attenuated the TGF-β1 expression both in hair follicles and DPCs. Furthermore, ginsenoside Rb1 facilitated the activation of PI3K/AKT/GSK-3β signaling pathway in hair follicles and DPCs., Significance: The results reveals a crucial role of PI3K/AKT/GSK-3β signaling pathway in ginsenoside Rb1-induced growth of hair follicles and DPCs., (Copyright © 2019. Published by Elsevier Inc.)

Androgenetic alopecia (AGA) is the most common form of hair loss disorder. As the prevalence of AGA rises, the demand for AGA treatments is rising accordingly, prompting research to identify therapeutic candidates to treat AGA. Because AGA is caused by crosstalk among multiple hair follicle (HF) cell components, understanding the effects of candidate molecules on HF cells is essential to determining therapeutic candidates for treatment. To date, research has centered on HF dermal papilla and outer root sheath cells and has indicated that the hair growth effects of candidate substances may be mediated via alterations in several signaling pathways and signature genes in these HF cells. In more integrative evaluations, the HF unit is used as an ex vivo organ culture model to verify the effects of therapeutic candidates. Animal models have also been used to evaluate the effects of candidate substances. The main outcomes used to evaluate the effects of candidate substances are 1) changes in HF growth rates in vitro, 2) anagen induction capabilities, and 3) the effects of androgen modulation. This article reviews a series of methods used to evaluate the hair growth-promoting effects of candidate substances, providing an overview of cell assays, organs, and animal models used in AGA research in order to facilitate AGA research moving forward., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study developed lipid nanocarriers, called squarticles, conjugated with anti-platelet-derived growth factor (PDGF)-receptor β antibody to determine whether targeted Minoxidil (MXD) delivery to the follicles and dermal papilla cells (DPCs) could be achieved. Squalene and hexadecyl palmitate (HP) were used as the matrix of the squarticles. The PDGF-squarticles showed a mean diameter and zeta potential of 195 nm and -46 mV, respectively. Nanoparticle encapsulation enhanced MXD porcine skin deposition from 0.11 to 0.23 μg/mg. The antibody-conjugated nanoparticles ameliorated follicular uptake of MXD by 3-fold compared to that of the control solution in the in vivo mouse model. Both vertical and horizontal skin sections exhibited a wide distribution of nanoparticles in the follicles, epidermis, and deeper skin strata. The encapsulated MXD moderately elicited proliferation of DPCs and vascular endothelial growth factor (VEGF) expression. The active targeting of PDGF-squarticles may be advantageous to improving the limited success of alopecia therapy., From the Clinical Editor: Topical use of minoxidil is only one of the very few treatment options for alopecia. Nonetheless, the current delivery method is far from ideal. In this article, the authors developed lipid nanocarriers with anti-platelet-derived growth factor receptor ? antibody to target dermal papilla cells, and showed enhanced uptake of minoxidil., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Dermal papilla (DP) cells may be the source of dermal-derived signaling molecules involved in hair-follicle development and postnatal hair cycling. Early-passage DP cells can induce hair growth in vivo, but, on further culture, this ability is lost. The cellular mechanisms underlying the hair-follicle induction property of early-passage DP cells are unclear. Long noncoding RNAs (lncRNAs) are an important class of genes involved in various biological functions. They are aberrantly expressed and play roles in the regulation of the Wnt signaling pathway, a critical point in maintaining hair-induction activity. LncRNA microarray revealed 1683 upregulated and 1773 downregulated lncRNAs in passage-4 DP cells compare with passage-10 DP cells. To investigate the relation between lncRNAs and coding genes in WNT signaling, we constructed a coding-noncoding gene co-expression network using lncRNAs and coding genes that were differentially expressed between the passage-4 and -10 DP cells. RP11-766N7.3, H19 and HOTAIR are specific lncRNAs that were aberrantly expressed in DP cells and played an important role in regulating Wnt signaling. This study may provide potential targets for discovering the hair-follicle induction mechanism of early-passage DP cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Broad dermal Wnt signaling is required for patterned induction of hair follicle placodes and subsequent Wnt signaling in placode stem cells is essential for induction of dermal condensates, cell clusters of precursors for the hair follicle dermal papilla (DP). Progression of hair follicle formation then requires coordinated signal exchange between dermal condensates and placode stem cells. However, it remains unknown whether continued Wnt signaling in DP precursor cells plays a role in this process, largely due to the long-standing inability to specifically target dermal condensates for gene ablation. Here we use the Tbx18(Cre) knockin mouse line to ablate the Wnt-responsive transcription factor β-catenin specifically in these cells at E14.5 during the first wave of guard hair follicle formation. In the absence of β-catenin, canonical Wnt signaling is effectively abolished in these cells. Sox2(+) dermal condensates initiate normally; however by E16.5 guard hair follicle numbers are strongly reduced and by E18.5 most whiskers and guard hair follicles are absent, suggesting that active Wnt signaling in dermal condensates is important for hair follicle formation to proceed after induction. To explore the molecular mechanisms by which Wnt signaling in dermal condensates regulates hair follicle formation, we analyze genome-wide the gene expression changes in embryonic β-catenin null DP precursor cells. We find altered expression of several signaling pathway genes, including Fgfs and Activin, both previously implicated in hair follicle formation. In summary, these data reveal a functional role of Wnt signaling in DP precursors for embryonic hair follicle formation and identify Fgf and Activin signaling as potential effectors of Wnt signaling-regulated events., (© 2013 Published by Elsevier Inc.)