Researchers identify exosomal microRNA that shows promise for hair regrowth

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

Hair growth depends on the health of dermal papillae (DP) cells, which regulate the hair follicle growth cycle. Current treatments for hair loss can be costly and ineffective, ranging from invasive surgery to chemical treatments that don’t produce the desired result. Recent hair loss research indicates that hair follicles don’t disappear where balding occurs, they just shrink. If DP cells could be replenished at those sites, the thinking goes, then the follicles might recover.

A research team led by Ke Cheng, Randall B. Terry, Jr. Distinguished Professor in Regenerative Medicine at NC State’s College of Veterinary Medicine and professor in the NC State/UNC Joint Department of Biomedical Engineering, cultured DP cells both alone (2D) and in a 3D spheroid 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 looked at how quickly hair regrew on mice treated with 2D cultured DP cells, 3D spheroid-cultured DP cells in a keratin scaffolding, and the commercial hair loss treatment Minoxidil. In a 20-day trial, mice treated with the 3D DP cells had regained 90% of hair coverage at 15 days.

“The 3D cells in a keratin scaffold performed best, as the spheroid mimics the hair microenvironment and the keratin scaffold acts as an anchor to keep them at the site where they are needed,” Cheng says. “But we were also interested in how DP cells regulate the follicle growth process, so we looked at the exosomes, specifically, exosomal miRNAs from that microenvironment.” Exosomes are tiny sacs secreted by cells that play an important role in cell to cell communication. Those sacs contain miRNAs.

MiRNAs are small molecules that regulate gene expression. Cheng and his team measured miRNAs in exosomes derived from both 3D and 2D DP cells. In the 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 hair follicle growth, while inhibiting it caused the follicles to lose function.

Effects of exosome treatment on dorsal hair regrowth

(A) Mice were divided into three groups (n = 4) and treated on their left sides. Mice were imaged on days 10 and 15, respectively. (B) Corresponding hair coverage analysis of different groups. Both the left and right sides were recorded. 3D DP-XOs promoted hair follicle growth more effectively than minoxidil and 2D DP-XOs. n = 4; *P < 0.05, **P < 0.01, and ***P < 0.001. (C) Immunofluorescence costaining of SFRP2 (green) and β-catenin (red) on skin samples from different treatment groups. Nuclei were stained by DAPI (4′,6-diamidino-2-phenylindole) (blue). Scale bars, 100 μm. (D) Quantification of the relative expression of SFRP2. n = 5; ****P < 0.0001. (E) Representative mice imaged on day 20 after injection of negative control, miR-218-5p mimics, and inhibitors, respectively. Red circles indicate injection spots. There is a small bald spot on the injection site, which means that the delivery approach needs further modification. (F) Quantification of hair coverage level (%) of three groups on day 15. n = 4; *P < 0.05 and **P < 0.01. (G) miR-218-5p up-regulated exosomes and miR-218-5p mimics delivered via in vivo-jetPEI can transfect miR-218-5p to target SFRP2 and thus up-regulate the WNT/β-catenin pathway; miR-218-5p inhibitor will block this signaling to a certain degree. Photo credit: S.H., North Carolina State University.

“Cell therapy with the 3D cells could be an effective treatment for baldness, but you have to grow, expand, preserve and inject those cells into the area,” Cheng says. “MiRNAs, on the other hand, can be utilized in small molecule-based drugs. So potentially you could create a cream or lotion that has a similar effect with many fewer problems. Future studies will focus on using just this miRNA to promote hair growth.”

Source – North Carolina State University

Hu S, Li Z, Lutz H, Huang K, Su T, Cores J, Dinh PUC, Cheng K. (2020) Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling. Sci Adv 6(30), eaba1685. [article]

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