90 percent of lost hair can be restored with miRNA therapy

Hair growth depends on the health of the dermal papilla (DP) cells, which regulate the growth cycle of hair follicles. (CREDIT: Creative Commons)

People suffering from moderate hair loss turn to topical treatments such as minoxidil (an antihypertensive drug that opens potassium channels) and finasteride (a 5α-reductase inhibitor that suppresses dihydrotestosterone), the only FDA-approved treatments for hair loss. stimulating hair growth. Both are not meant to treat hair loss, but rather a fluke.

Researchers at North Carolina State University have identified a microRNA (miRNA) that can promote hair regeneration. This siRNA, miR-218-5p, plays an important role in regulating a pathway involved in follicle regeneration and may be a candidate for future drug development.

Hair growth depends on the health of the dermal papilla (DP) cells, which regulate the growth cycle of hair follicles. Current treatments for hair loss can be costly and ineffective, ranging from invasive surgery to chemical treatments that don’t work. Recent hair loss research shows that hair follicles do not disappear with baldness, but simply shrink. If DP cells could be replenished at these locations, then the follicles could regenerate.

A research team led by Ke Cheng, Randall B. Terry, Jr., Distinguished Professor of Regenerative Medicine at the NC State Veterinary Medicine College and Professor at the NC State and University of North Carolina Joint School of Biomedical Engineering, cultured DP cells both singly (2D) and and in a three-dimensional spheroidal medium. The spheroid is a three-dimensional cellular structure that effectively recreates the natural microenvironment of the cell.

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In a mouse hair regeneration model, Cheng observed how rapidly hair regrowth was observed in mice treated with 2D cultured DP cells, 3D cultured spheroid DP cells in a keratin scaffold, and the commercial hair loss drug minoxidil. In a 20-day trial, mice treated with 3D DP cells recovered 90% of their hairline after 15 days.

“Three-dimensional cells in a keratin scaffold performed best because the spheroid mimics the hair microenvironment, and the keratin scaffold acts as an anchor, holding them where they are needed,” says Cheng. “But we were also interested in how DP cells regulate the process of follicle growth, so we looked at exosomes, specifically exosomal miRNAs from this microenvironment.” Exosomes are tiny sacs secreted by cells that play an important role in cell-to-cell communication. These sacs contain miRNAs.

MicroRNAs are small molecules that regulate gene expression. Cheng and his team measured miRNAs in exosomes derived from both 3D and 2D DP cells. In exosomes derived from 3D DP cells, they found miR-218-5p, a miRNA that enhances the molecular pathway responsible for stimulating hair follicle growth. They found that increasing the amount of miP-218-5p promotes the growth of hair follicles, and its inhibition leads to loss of follicular function.

Preparation and characterization of 3D DP spheroids. (A) Isolation of mouse dermal papilla (DP) cells from vibrissae. Scale bar, 500 µm. (B) Conventional culture allows 2D DP cells to be grown. Scale bar, 50 µm. (C) Growth of DP spheroids in ultra-low 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-laden keratin. (F) One apparent spheroid is highlighted in yellow. Scale bars, 100 µm. (G) Scheme illustrating injection sites on the back of a mouse for cell retention studies. (H) The mouse was shaved and various formulations were injected into the back skin as shown in (G). Cells were labeled with DiD and then resuspended in PBS or keratin for intradermal injection. Images of the in vivo imaging system (IVIS) were obtained at different time points. (I) Quantification of IVIS images. Data are presented as mean ± standard deviation, n = 3 mice. 3D spheroids/keratin showed the longest retention time. (TEACHER: Ke Cheng, North Carolina State University)

“Cell therapy with 3D cells can be an effective treatment for hair loss, but you have to grow, expand, preserve, and inject these cells into the area,” Cheng says.

Effect of exosome treatment on back hair regrowth. (A) Mice were divided into three groups (n = 4) and treated on the left side. Mice were visualized on days 10 and 15, respectively. (TEACHER: Ke Cheng, North Carolina State University)

“On the other hand, miRNAs can be used in small molecule drugs. So you could potentially create a cream or lotion with the same effect but with fewer problems. Future research will focus on using this siRNA alone to stimulate hair growth.”

The study appears in Scientific achievementsand was supported by the National Institutes of Health and the American Heart Association. Cheng is the corresponding author. Postdoctoral fellow Shiqi Hu is the first author.

This study was performed in part at the Center for Analytical Instrumentation (AIF) at North Carolina State University, which is supported by the State of North Carolina and NSF (award number ECCS-1542015).

This work used AIF equipment purchased with support from NSF (DMR-1726294). AIF is a member of the North Carolina Research Triangle Nanotechnology Network (RTNN), a site within the National Coordinated Nanotechnology Infrastructure (NNCI).

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Note: Materials provided by North Carolina State University. Content can be edited for style and length.

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