[Aug 13, 2022: Ke Cheng, NC State University]
Hair growth depends on the health of dermal papilla (DP) cells, which control the hair follicle growth cycle. (credit: creative commons)
Those affected by moderate hair loss turn to topical treatments such as minoxidil (an antihypertensive potassium channel opener) and finasteride (dihydrotestosterone-suppressing 5α-reductase inhibitor), the only Food and Drug Administration-approved treatments for regrow hair. Both are not made for the treatment of hair loss but for the severity.
Researchers at North Carolina State University have identified a microRNA (miRNA) that may promote hair regeneration. This miRNA – miR-218-5p – plays an important role in regulating the pathway involved in follicle regeneration, and may be a candidate for future drug development.
Hair growth depends on the health of dermal papilla (DP) cells, which control the hair follicle growth cycle. Current treatments for hair loss can be costly and ineffective, ranging from invasive surgery to chemical treatments that do not produce the desired results. Recent hair loss research indicates that hair follicles do not disappear where balding occurs, they simply shrink. If the DP cells at those sites can be replenished, the thinking goes, then the follicles can heal.
A research team led by Ke Cheng, Randall B. Terry, Jr. Distinguished Professor in Regenerative Medicine at NC State College of Veterinary Medicine and professor in the NC State/UNC Joint Department of Biomedical Engineering, cultured DP cells both alone (2D) and in the NC State/UNC Joint Department of Biomedical Engineering. in a 3D spherical environment. A spheroid is a three-dimensional cellular structure that effectively recreates a cell’s natural microenvironment.
In a mouse model of hair regeneration, Cheng observed how quickly hair regrows on mice treated with 2D cultured DP cells, 3D spheroid-cultured DP cells in a keratin scaffold, and the commercial hair loss treatment minoxidil. In a 20-day test, mice treated with 3D DP cells had achieved 90% hair coverage by 15 days.
“3D cells performed best in the keratin scaffold, because the spheroid mimics the microenvironment of the hair and the keratin scaffold acts as an anchor to hold them where they are needed,” says Cheng. ” “But we were also interested in how DP cells control the follicle development process, so we looked at exosomes, specifically, exosomal miRNAs from that microenvironment.” Exosomes are small sacs secreted by cells that play an important role in cell-to-cell communication. Those sacs contain miRNAs.
MiRNAs are small molecules that control gene expression. Cheng and his team measured the miRNAs in exosomes derived from 3D and 2D DP cells. In 3D DP cell-derived exosomes, they pinpointed miR-218-5p, a miRNA that enhances the molecular pathway responsible for promoting hair follicle growth. They found that increasing miR-218-5p promoted the growth of hair follicles, while inhibiting it eliminated the function of the follicles.
Preparation and characterization of 3D DP spheroids. (A) Isolation of mouse dermal papilla (DP) cells by vibration. Scale bar, 500 µm. (B) Conventional culture enables the growth of 2D DP cells. Scale bar, 50 µm. (C) Growth of DP spheroids in ultralow cell culture flasks. Scale bar, 100 µm. (D) Double staining of CD133 (green) and β-catenin (red) in spheroids. Scale bar, 100 µm. (E and F) Scanning electron microscopy (SEM) images of keratin (E) and 3D spheroid-loaded keratin. (f) A clear spheroid is highlighted in yellow. Scale bar, 100 µm. (g) Schematic showing the injection sites on the back of the mouse for cell retention studies. (H) The mouse was shaved and injected with different formulations on the dorsal skin as shown in (G). Cells were labeled by DiD and then resuspended in PBS or keratin for intradermal injection. Images were taken at different time points with an in vivo imaging system (IVIS). (I) Quantification of IVIS images. Data are shown as the mean ± SD, n = 3 mice. 3D spheroids/keratin showed the longest retention time. (Credit: Ke Chang, NC State University)
“Cell therapy with 3D cells can be an effective treatment for baldness, but you have to grow, expand, protect, and inject those cells into the area,” Cheng says. “MiRNAs, on the other hand, could be used in small molecule-based drugs. So potentially you could create a cream or lotion that has the same effect with far fewer problems. Future studies may be able to promote hair growth.” Will focus on using only this miRNA for
Effects of exosome treatment on dorsal hair regrowth. (A) Rats were divided into three groups (n = 4) and treated on their left side. Mice were imaged on days 10 and 15, respectively. (Credit: Ke Chang, NC State University)
appears in research science advance, and was supported by the National Institutes of Health and the American Heart Association. Cheng is the corresponding author. Postdoctoral researcher Shiki Hu is the first author.
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Comment: Materials provided by NC State University. Content can be edited for style and length.
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