Stem cells to fight hair loss

A variant of a drug used in diabetes treatment helps regeneration of hair follicles by manipulating stem cell metabolism…

Stem cells divide continually to repair and replace tissues throughout our lifetimes. The ability to manipulate them therefore offers us an opportunity to use them for regenerative medicine, to replace tissue which has been damaged or is otherwise unable to carry out its function.

A useful model for studying how stem cells can do this is the hair follicle. In the follicle, stem cells divide to form specialised cells which, in turn, produce the actual hair. The follicles cycle through growth, regression and rest phases. But whether through stress, chemotherapy or genetics, hair follicles can be lost, leading to hair loss, which can cause great emotional distress. This psychological impact drives the need for improved treatment.

Now Myung Jin Son and a team from the Stem Cell Research Centre at the Korea Research Institute of Bioscience and Biotechnology have successfully made a small molecule - dubbed “IM” - which enhances hair regrowth by shifting cell metabolism towards stem-cell-like activity. 

In mice, IM increased hair regrowth after depilation by pushing hair follicles into their growth phase. This was preceded by the appearance of colonies of stem cells, which produced more follicles.

Stem cells generate most of their energy through an oxygen-independent process called glycolysis. This is distinct from more specialised - or differrentiated - cells, which instead favour mitochondrial respiration. IM mildly inhibits mitochondrial activity, leading to a compensatory increase in oxygen-independent glycolysis. This same switch has previously been shown to favour transition towards a stem-like state.

IM treatment is also associated with the activation of stem-cell specific genes and signaling from surrounding supportive cells. This illustrates the crosstalk between metabolism, gene expression and signals from surrounding cells, and how feedback loops between these define the stem cell state. Insights from these experiments may be applicable to cell reprogramming in other contexts.

Furthermore, IM showed equal or higher efficacy than existing treatments in males and females respectively. These results highlight how hormones affect tissue growth and regeneration, and the importance of considering stem cells cellular context. IM may be a particularly useful molecule as there are currently fewer hair loss treatment options for women.

Interestingly, IM is part of the same class of drugs as metformin, a drug which currently widely prescribed for type 2 diabetes, and is able to influence cell metabolism at much lower concentrations. This illustrates how variations on existing compounds can be redirected for new applications, an exciting area in pharmacology today.