Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth

Chen, Yuxin; Huang, Junfei; Chen, Ruosi; Yang, Lunan; Wang, Jin; Liu, Bingcheng; Du, Lijuan; Yi, Yanhua; Jia, Jingyi; Xu, Yongdong; Chen, Qian; Ngondi, Djakaya Guydidier; Miao, Yong; Hu, Zhiqi

doi:10.7150/thno.39566

Cited by 53 publications

(45 citation statements)

References 61 publications

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“…The differentially expressed secretome or exosomes from DP spheroids and DP cells could be the key to regulating hair follicle cycles. Recently, DP cell–derived secretome and extracellular vesicles ( 8 , 19 , 20 ) have demonstrated their effect in promoting hair growth, and their mechanism is under immense investigation. Compared with mesenchymal stem cell–derived exosomes ( 8 , 21 ), DP cell–derived exosomes were demonstrated to be efficient transforming growth factor–β activators and proven to be important in promoting proliferation of human hair follicle DP cells and hair growth ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

et al. 2020

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The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

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Section: Introductionmentioning

confidence: 99%

Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

et al. 2020

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“…It is estimated that 50% of men and 25% of women worldwide suffer from hair loss, and currently, transplantation of autologous hair follicles has become the main treatment strategy for this hair loss 1 , 2 . However, for patients without adequate autologous hair follicles, the transplantation of heterologous hair follicles remains ineffective 3 .…”

Section: Introductionmentioning

confidence: 99%

Single-cell Transcriptome Profiling reveals Dermal and Epithelial cell fate decisions during Embryonic Hair Follicle Development

Ge¹,

Tan²,

Wang³

et al. 2020

Theranostics

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It is estimated that 50% of men and 25% of women worldwide suffer from hair loss, and therefore it is of great significance to investigate the molecular pathways driving hair follicle de novo morphogenesis. However, due to high cellular heterogeneity and the asynchronous development of hair follicles, our current understanding of the molecular mechanisms involved in follicle development remains limited. Methods: Single-cell suspensions from the dorsal skin of E13.5 (induction stage), E16.5 (organogenesis) fetal mice, and newborn mice (cytodifferentiation stage, postnatal day 0, P0) were prepared for unbiased single-cell RNA sequencing. To delineate the single-cell transcriptional landscape during hair follicle de novo morphogenesis, we performed t-distributed Stochastic Neighbor Embedding (tSNE), pseudotime cell trajectory inference, and regulon enrichment analysis to dissect cellular heterogeneity and reveal the molecular pathways underlying major cell type cell fate decisions. To validate our analysis, we further performed immunohistochemistry analysis of the key molecules involved during hair follicle morphogenesis. Meanwhile, intercellular communication between different cell populations was inferred based on a priori knowledge of ligand-receptor pairs. Results: Based on tSNE analysis, we identified 14 cell clusters from skin tissue and delineated their cellular identity from specific gene expression profiles. By using pseudotime ordering analysis, we successfully constructed the epithelium/dermal cell lineage differentiation trajectory. For dermal cell lineage, our analysis here recapitulated the dynamic gene expression profiles during dermal condensate (DC) cell fate commitment and delineated the heterogeneity of the different dermal papilla (DP) cell populations during in utero hair follicle development. For the epithelium cell lineage, our analysis revealed the dynamic gene expression profiles of the underappreciated matrix, interfollicular epidermis (IFE), hair shaft and inner root sheath (IRS) cell populations. Furthermore, single-cell regulatory network inference and clustering analysis revealed key regulons during cell fate decisions. Finally, intercellular communication analysis demonstrated that strong intercellular communication was involved during early hair follicle development. Conclusions: Our findings here provide a molecular landscape during hair follicle epithelium/dermal cell lineage fate decisions, and recapitulate the sequential activation of core regulatory transcriptional factors (TFs) in different cell populations during hair follicle morphogenesis. More importantly, our study here represents a valuable resource for understanding the molecular pathways involved during hair follicle de novo morphogenesis, which will have implications for future hair loss treatments.

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“…Previous studies focus on the facilitation of hair regrowth using EVs or exosomes. Hu et al prepared an oxidized sodium alginate hydrogel encapsulating dermal papilla cell-derived extracellular vesicles (DP-EVs) [18] . The release system facilitated hair regrowth in vivo and in vitro resulting from upregulation of hair growth-promoting signaling molecules such as β-catenin and Wnt3a, and downregulation of inhibitory molecule BMP2.…”

Section: Discussionmentioning

confidence: 99%

“…As previous reports, mesenchymal stem cell (MSC)-derived EVs could promote wound healing by inducing proliferation and migration of broblast, as well as angiogenesis in vitro [16] .According to Rajendran et al, MSC-derived EVs (MSC-EVs) have a potential to activate DP cells, prolonged survival, induce growth factor activation in vitro, and promotes hair growth in vivo [17] . It is reported that oxidized-sodium-alginate (OSA)-encapsulated EVs could increase the level of Wnt3a and β-catenin, which might be used to treat alopecia [18] . In addition, it has been shown that exosomes from bone marrow cells (BMC) prevent alopecia areata (AA) progression and su ced for partial hair regrowth [19] .These studies show that EVs may play an important role in hair growth cycle by regulating certain signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Neural progenitor cell-derived nanovesicles promote hair follicle growth via miR-100

Cao

Tian

Huang

et al. 2020

Preprint

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Background: Accumulating evidence shows that mesenchymal stem cell-derived extracellular vesicles (EVs) hold great promise to promote hair growth. However, large-scale production of EVs is still a challenge. Recently, exosome-mimetic nanovesicles (NV) prepared by extruding cells have emerged as an alternative strategy for clinical-scale production. Here, ReNcell VM (ReN) cells, a neural progenitor cell line was serially extruded to produce NV. Results: The ReN-NV were found to promote dermal papilla cell (DPC) proliferation. In addition, in a mouse model of depilation-induced hair regeneration, ReN-NV were injected subcutaneously, resulting in an acceleration of hair follicle (HF) cycling transition at the site. The underlying mechanism was indicated to be the activation of Wnt/β-catenin signaling pathway. Furthermore, miR-100 was revealed to be abundant in ReN-NV and significantly up-regulated in DPCs receiving ReN-NV treatment. miR-100 inhibition verified its important role in ReN-NV-induced β-catenin signaling activation. Conclusion: These results provide an alternative agent to EVs and suggest a strategy for hair growth therapy.

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Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth

Cited by 53 publications

References 61 publications

Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

Single-cell Transcriptome Profiling reveals Dermal and Epithelial cell fate decisions during Embryonic Hair Follicle Development

Neural progenitor cell-derived nanovesicles promote hair follicle growth via miR-100

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