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

Abstract

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 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.

Application of Cell-Derived Extracellular Vesicles and Engineered Nanovesicles for Hair Growth: From Mechanisms to Therapeutics

“…Furthermore, miR-100 inhibition verified its key role in ReN-NV-induced β-catenin signaling activation. This study provides the potential for large-scale production of NVs for hair growth therapies ( Cao et al, 2021 ).…”

“…In addition, fibroblast-derived EVs induced ORSC differentiation by increasing the transcriptional expression of keratins ( Rajendran et al, 2021b ), whereas activated fibroblast-derived EVs regulated the Norrin-encoding genes of DPCs ( Riche et al, 2019 ). Another study showed that human neural progenitor cell - derived EVs containing miR-100-5p increased the levels of β-catenin, C-myc, and Cyclin D1 in DPCs and these effects were abolished when miR-the DPCs were treated with miR-100-5p inhibitors ( Cao et al, 2021 ). Finally, mouse ADSC-derived EVs were shown to carry low levels of miR-22-5p and miR-22-3p; use of inhibitors against miR-22 diminished the hair inductive ability ( Li et al, 2022 ).…”

“…Although neural progenitor cells have been used as a cell source for eNVs, these would be hard to acquire from human subjects ( Cao et al, 2021 ). Several studies have used bone marrow MSCs and ADSCs as an EV source for hair growth; both these cells are good sources for EVs for hair growth as they available at considerable scale compared with DPCs or neural progenitor cells ( Rajendran et al, 2017 ; Gangadaran et al, 2021 ).…”

Dermal Papilla Cell-Derived Extracellular Vesicles Increase Hair Inductive Gene Expression in Adipose Stem Cells via β-Catenin Activation

“…CTNB plays an important role in cell cycle progression, cell proliferation, and gene regulation of Cyclind1 and c-Myc , as well as Ctnb . Upon Ctnb activation, it accumulates cytoplasm and translocates into the nucleus [ 34 ], and then transcriptionally regulates various events, such as the maintenance of the HF anagen phase [ 35 ].…”

Extracellular Vesicles: Emerging Therapeutics in Cutaneous Lesions

“…Cao et al injected NV extruded from ReNcell VM (ReN) cells, a neural progenitor cell line, in a mouse model. 92 The results showed that the NV promoted the proliferation of DPC and accelerated HF cycling transition by miR-100 to activate the Wnt/β-catenin signaling pathway. 92 This study therefore highlighted a possible method for the large-scale production of EVs in future.…”