Extracellular vesicles derived from MSCs activates dermal papilla cell in vitro and promotes hair follicle conversion from telogen to anagen in mice

Rajendran, Ramya Lakshmi; Gangadaran, Prakash; Bak, Soon Sun; Oh, Ji Min; Kalimuthu, S; Lee, Ho Won; Baek, Se Hwan; Zhu, Li; Sung, Young Kwan; Jeong, Shin Young; Lee, Sang‐Woo; Lee, Jaetae; Ahn, Byeong‐Cheol

doi:10.1038/s41598-017-15505-3

Cited by 145 publications

(131 citation statements)

References 75 publications

(77 reference statements)

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“…In addition to the present study, three groups have recently reported that EVs derived from either MSCs or DPCs activated β‐catenin and/or sonic hedgehog pathways in vitro and HF growth in vivo through telogen reactivation . It confirms that EVs participate to the cell–cell communications that occur during HF physiology and cycling.…”

Section: Resultssupporting

confidence: 85%

Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin

Riche

Aberdam

Marchand³

et al. 2019

Stem Cells

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Dermal papilla cells (DPCs) play a pivotal role in the regulation of hair follicle (HF) growth, formation, and cycling, mainly through paracrine mechanisms. In the last decade, extracellular vesicles (EVs) have been recognized as a new paracrine mechanism that can modify the physiological state of recipient cells by transferring biological material. Herein, we investigated the effect of EVs isolated from stimulated human dermal fibroblasts (DFs) on DPC activation and HF growth. We found that these EVs (st-EVs) enhanced HF growth ex vivo. Comparative transcriptomic analysis on DPCs identified specific activation of the NDP gene, encoding the non-Wnt ligand Norrin. We found that Norrin was secreted by st-EVs-stimulated DPCs activating in a noncell autonomous manner β-catenin pathway in follicular keratinocytes (human HF keratinocyte [HHFK]) and hair growth ex vivo. Although Norrin-specific receptor Frizzled4 was barely detected in HHFK, we found its presence in DF-EVs. Accordingly, DF-EVs provided Frizzled4 to potentiate Norrin effects ex vivo. Our study identifies DF-EVs as efficient activators of DPCs and Norrin as a novel modulatory player in HF physiopathology. STEM CELLS 2019;37:1166-1175 SIGNIFICANCE STATEMENTDermal papilla cells (DPCs) control the growth and regeneration of hair follicles (HFs) via cellcell interactions and extracellular molecules. These data demonstrate that activated dermal fibroblasts (DFs) secrete specific extracellular vesicles (st-EVs) that enhance HF growth ex vivo. DPCs treated with st-EVs secrete Norrin, a non-Wnt ligand that activates the β-catenin pathway of recipient human hair follicular keratinocytes. DF-EVs contain Norrin-specific Frizzled4 receptor that is barely detected in human HF keratinocytes. Combinatory treatment of Norrin and DF-EVs is sufficient to recapitulate the stimulating effect ex vivo of st-EVs on HF growth. The study identifies Norrin as a novel modulatory player in HF physiopathology.

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Section: Resultssupporting

confidence: 85%

Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin

Riche

Aberdam

Marchand³

et al. 2019

Stem Cells

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“…The conditioned medium secreted by stem cells also act as a highly enriched source of growth factors that stimulates hair growth. The hair growth promoting effects of stem cells and conditioned medium have been mediated via activation of DPCs .…”

Section: Hair Growth Promoting Effectmentioning

confidence: 99%

Review of Hair Follicle Dermal Papilla cells asin vitroscreening model for hair growth

Madaan

Verma

Singh

et al. 2018

Intern J of Cosmetic Sci

112

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Hair disorders such as hair loss (alopecia) and androgen dependent, excessive hair growth (hirsutism, hypertrichosis) may impact the social and psychological well-being of an individual. Recent advances in understanding the biology of hair have accelerated the research and development of novel therapeutic and cosmetic hair growth agents. Preclinical models aid in dermocosmetic efficacy testing and claim substantiation of hair growth modulators. The in vitro models to investigate hair growth utilize the hair follicle Dermal Papilla cells (DPCs), specialized mesenchymal cells located at the base of hair follicle that play essential roles in hair follicular morphogenesis and postnatal hair growth cycles. In this review, we have compiled and discussed the extensively reported literature citing DPCs as in vitro model to study hair growth promoting and inhibitory effects. A variety of agents such as herbal and natural extracts, growth factors and cytokines, platelet-rich plasma, placental extract, stem cells and conditioned medium, peptides, hormones, lipid-nanocarrier, light, electrical and electromagnetic field stimulation, androgens and their analogs, stress-serum and chemotherapeutic agents etc. have been examined for their hair growth modulating effects in DPCs. Effects on DPCs' activity were determined from untreated (basal) or stress induced levels. Cell proliferation, apoptosis and secretion of growth factors were included as primary end-point markers. Effects on a wide range of biomolecules and mechanistic pathways that play key role in the biology of hair growth were also investigated. This consolidated and comprehensive review summarizes the up-to-date information and understanding regarding DPCs based screening models for hair growth and may be helpful for researchers to select the appropriate assay system and biomarkers. This review highlights the pivotal role of DPCs in the forefront of hair research as screening platforms by providing insights into mechanistic action at cellular level, which may further direct the development of novel hair growth modulators.

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“…Maintenance of anagen, in contrast, is controlled by insulin-like growth factor-1, hepatocyte growth factor, and vascular endothelial growth factor (VEGF) [54]. As anagen progresses, the bulge reverts to a Wnt-inhibited state [55], and Wnt inhibition by TCF3, Wnt inhibitory factor 1 and Dkks (e.g., Dkk3) and the calcium-dependent transcription factor NFATc1 [56] maintain bulge stem cells in a quiescent state [7].…”

Section: Anagenmentioning

confidence: 99%

Molecular Mechanisms of Hair Growth and Regeneration: Current Understanding and Novel Paradigms

et al. 2020

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Hair is a defining feature of mammals and has critical functions, including protection, production of sebum, apocrine sweat and pheromones, social and sexual interactions, thermoregulation, and provision of stem cells for skin homeostasis, regeneration, and repair. The hair follicle (HF) is considered a “mini-organ,” consisting of intricate and well-organized structures which originate from HF stem and progenitor cells. Dermal papilla cells are the main components of the mesenchymal compartments in the hair bulb and are instrumental in generating signals to regulate the behavior of neighboring epithelial cells during the hair cycle. Mesenchymal-epithelial interactions within the dermal papilla niche drive HF embryonic development as well as the postnatal hair growth and regeneration cycle. This review summarizes the current understanding of HF development, repair, and regeneration, with special focus on cell signaling pathways governing these processes. In particular, we discuss emerging paradigms of molecular signaling governing the dermal papilla-epithelial cellular interactions during hair growth and maintenance and the recent progress made towards tissue engineering of human hair follicles.

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Extracellular vesicles derived from MSCs activates dermal papilla cell in vitro and promotes hair follicle conversion from telogen to anagen in mice

Cited by 145 publications

References 75 publications

Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin

Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin

Review of Hair Follicle Dermal Papilla cells asin vitroscreening model for hair growth

Molecular Mechanisms of Hair Growth and Regeneration: Current Understanding and Novel Paradigms

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