Hair Growth Activated By Modifying Immune Cells

This is a skin whole mount section showing hair follicles (blue)
surrounded by clusters of skin resident macrophages (red).
The molecular communication between macrophages and hair
follicle stem cells regulates the initiation of hair follicle growth.
(Credit: Donatello Castellana, CNIO)
A discovery, published in PLOS Biology, reveals a novel angle to spur hair follicle growth. This also adds new knowledge to a broader problem: how to regenerate tissues in an adult organism, especially the skin.
 
The group has discovered an unexpected connection - a link between the body's defense system and skin regeneration. According to the authors, cells from the immune system called macrophages - those in charge of devouring invading pathogens, for example - are also responsible for activating skin stem cells and induce hair growth.
 
The regenerative ability of stem cells allows skin replenishment during a lifetime. But different factors can reduce their regenerative properties or promote their uncontrolled growth. When things go wrong, this can lead to aging and disease, including skin carcinomas. The discovery that macrophages activate skin stem cells may also have further implications beyond the possibility to develop therapeutic approaches for hair loss, but may also be relevant for cancer research.
 
The research emerged more than four years ago from an observation made by the researchers while working on another project. The mice they had been working with at that time received anti-inflammatory drugs, a treatment that also reactivated hair growth. Convinced that the explanation could reside in the existence of close communication between stem cells and immune cells - the researchers began to experiment with the different types of cells involved in the body´s defense system.
 
After years of investigation, they discovered that when stem cells are dormant, a fraction of macrophages die, due to a process known as apoptosis. This stimulated the secretion of factors from dying and living macrophages, which in turn activated stem cells, and that is when hairs began to grow again.
 
Reproducing the natural process

Macrophages secrete a number of factors including a class of proteins called Wnt. Researchers demonstrated the participation of macrophage-derived Wnts by artificially reproducing the natural process by treating macrophages with a Wnt inhibitor drug encapsulated in liposomes. As expected, when they used this drug, the activation of hair growth was delayed. 
 
Although this study has been completed in mice, the researchers believe their discovery "may facilitate the development of novel treatment strategies" for hair growth in humans. The possibility of attacking one type of cell to affect another might have broader applications that go beyond "just" growing hair. Furthermore, the use of liposomes as a way of drug delivery to specific cells, is a very promising line of experimentation, which may have implications for the study of several pathologies.
 
From a more fundamental perspective, this research is an effort to understand how modifying the environment that surrounds adult skin stem cells can regulate their regenerative capabilities.
 

It is now known that macrophages are key cells involved in the biochemical dialogue that exists in the environment surrounding stem cells. The study underlines the importance of macrophages as modulators in skin regenerative processes, going beyond their primary function as phagocytes [immune system cells].
 
The researcher´s next goal is to characterise the class of macrophage(s) that are involved in the activation of skin stem cells and their implications in the regulation of stem cells under pathological conditions, including skin carcinomas.