A novel and safe small molecule enhances hair follicle regeneration by facilitating metabolic reprogramming

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells. Stem cells: A remedy to revitalize the roots A compound that establishes metabolic conditions favorable for sustaining stem cells may also offer a safe drug for promoting hair regrowth. Drugs that inhibit mitochondrial activity help lock stem cells into a pluripotent state that allows them to actively divide and repair various tissues, but many of these drugs are toxic. Researchers led by Myung Jin Son of the Korea Research Institute of Bioscience and Biotechnology, Daejeon and ImmunoMet, USA have identified a new compound that safely achieves the same effect. This potential drug helped promote stemness in diverse stem cell types, including the highly proliferative cells that comprise hair follicles. Topical application proved more effective at promoting hair regrowth in female mice than the baldness drug minoxidil, and matched its performance in males, demonstrating its potency as a stem cell modulator.