Hair Stenz cells study
Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β -catenin signaling
The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair re- growth. 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 b-catenin, promoting the development of hair follicles.
1- INTRODUCTION
People affected by moderate hair loss turn to topical treatments like minoxidil (antihypertensive potassium channel opener) (1) and fin- asteride (dihydrotestosterone-suppressing 5a-reductase inhibitor) (2), the only Food and Drug Administration–approved treatments for inducing hair regrowth. Both are designed not for hair loss treatment but serendipity. Researchers kept studying the mechanism of hair follicle cycles and designing small molecular drugs (3–5), bioproducts (6), formulations (7, 8), laser therapy (9), and surgical treatment (10) since neither minoxidil nor finasteride is very effective. Minoxidil and finasteride require constant reappli犀利士
cation by the user to main- tain hair growth (7). In their attempts to understand hair regrowth, many researchers have sought a more efficient approach by focusing on the hair follicle cycle. They have tried to stimulate a progression of the follicles from a resting phase (telogen) to an active phase (anagen) (8). Instead of follicular unit transplantation, which is costly and sometimes faces a shortage of donor hair follicles, researchers have attempted to use cell therapy to treat hair loss by culturing and proliferating hair follicle cells or mesenchymal cells in vitro and then implanting them in the bald area. In the anagen phase, the hair follicle bulge area is an abundant source of actively growing dermal papilla (DP) cells, which drop out during the resting phase. It has been suggested that hair follicles in bald areas are not disappearing but decreasing in size (11). The replenishment of DP cells to bald areas is, therefore, a plausible way to induce the telogen-to-anagen phase transition needed to induce hair growth.
The interactions between the epithelial and mesenchymal cells are vital in regulating the cycle of hair growth (12). As the main mesenchymal component of the follicular unit, DP cells induce the transition from telogen to anagen and the formation of new follicles. Thus, regulating DP cells is critical for increasing cell division and follicle growth rate. Two-dimensionally (2D) cultured DP cells have demonstrated no therapeutic effect on hair follicle growth (13). It has been reported that 3D spheroid cultures result in a partial resto- ration of the inductive capabilities of DP cells, which may enable them to induce de novo hair follicles in human skin (13). DP cells have to aggregate into hair follicle areas to be effective (14). Thus, spheroid culture therapy should be an effective way to regain the capacity for hair regeneration in vitro. However, a comprehensive understanding of the molecular mechanisms that underlie this re- generative process is required. DP cells induce the progression of the hair cycle and regeneration, which requires cross-talk with the surrounding environment (15). Exosomes have been extensively investigated because of their role in cell-cell communication and potential in treating diseases (16–18). 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 demon- strated to be efficient transforming growth factor–b activators and proven to be important in promoting proliferation of human hair follicle DP cells and hair growth (22). 3D culture has been proven to be a way to enrich certain proteins and microRNAs (miRNAs) in secretome (23). Young and co-workers (24) demonstrated that exo- somes derived from 3D DP cells (3D DP-XOs) promoted the prolif- eration of DP cells and outer root sheath cells and increased the expression of growth factors in DP cells. However, the importance of differentially expressed secretome and miRNAs from 2D DP cells and 3D DP cells and possible mechanisms of 3D DP cells or 3D DP-XOs in promoting hair regeneration have not been demonstrated. In this study, we first verified the hair restoration capacity of DP spheroids in C57BL/6 mice. Then, the therapeutic efficacy of DP secretome was compared with that of the DP spheroids. Different factors and exosomes were expressed when DP cells aggregate. Considering DP cells’ aggregative behavior and DP spheroids’ ability to induce new hair follicle formation in vivo, we hypothesized that the differ- entially expressed factors and miRNAs would be previously un- defined therapeutics for hair regrowth.
“Dermal exosomes containing miR-218-5p promote hair regeneration by regulating #-catenin signalin.”
– Shiqi HuZhenhua LiHalle LutzKe HuangTeng SuJhon CoresPhuong-Uyen Cao DinhKe Cheng