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CNIO researchers activate hair growth by modifying immune cells


How to restore hair loss is a task not undertaken exclusively by beauty practitioners. The discovery, now published by a group from the Spanish National Cancer Research Centre (CNIO), 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 of the study published today in PLOS Biology, 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 authors of the study are Mirna Perez-Moreno and Donatello Castellana, from the Epithelial Cell Biology Group of the BBVA Foundation-CNIO Cancer Cell Biology Programme, along with Ralf Paus, a hair immunobiology expert from the University of Manchester and Münster.

“We have discovered that macrophages, cells whose main function is traditionally attributed to fight infections and wound repair, are also involved in the activation of hair follicle stem cells in non inflamed skin,” says Perez-Moreno.


The researchers did not investigate the relationship between macrophages and hair for fun. This work emerged more than four years ago from an observation made by Perez-Moreno while working on another research project. The mice she 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 Perez-Moreno’s lab 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.


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, says Donatello Castellana.

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. “One of the current challenges in the stem cell field is to regulate the activation of endogenous stem cell pools in adult tissues to promote regeneration without the need of transplantation,” says Perez-Moreno.


It is now known that macrophages are key cells involved in the biochemical dialogue that exists in the environment surrounding stem cells.

“Our study underlines the importance of macrophages as modulators in skin regenerative processes, going beyond their primary function as phagocytes [immune system cells],” say the authors in PLoS Biology.

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.

As Perez-Moreno explains, “macrophages are a very diverse cell population. It was only less that ten years ago that scientists discovered that besides from the bone marrow, macrophages originate from the yolk sac during pregnancy, and there are even other macrophages that proliferate within tissues. The diversity of the sources from which skin resident macrophages originate is not fully understood.”

This work has been funded by the Ministry of Economy and Competitiveness, the Spanish Association against Cancer (AECC) and the BBVA Foundation.

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In 2014, we are able to restore sight to the blind and hearing to the deaf, but still figuring out a way to reverse hair loss eludes us. Well, 2015 may prove otherwise, as researchers in Spain believe they’ve found a way to spur new hair growth by using our body’s immune defense to stimulate stem cells in the surrounding skin.

Stem cell technology is being used for everything, from HIV treatment to reversing neurodegenerative disease, so why not try using it to tackle the much more common problem of hair loss. According to a recent press release, scientists have figured out a way to manipulate macrophages, a certain type of white blood cell, into reactivating hair follicles. The result? No more baldness.

In their study, published in PLOS Biology, the team succeeded in getting the macrophages to activate the stem cells in hair follicles on non-inflamed skin. The discovery was actually found by chance, when researchers realized that mice given anti-inflammatory drugs had the curious side effect of hair regrowth. Dr. Mirna Perex-Moreno, one of the researchers involved in the project, wondered if the hair growth was connected to the body’s immune reaction, and it turned out that she was right. Although macrophages are cells from the immune system which mainly help to fight infection and wound repair, it also seems that they play a role in activating the skin’s stem cells.

Although the study was carried out in mice, Dr. Mirna Perex-Moreno, the lead researcher, and her team are confident that similar results can be repeated in human subjects.

The study, although only in the very early stages, may be useful in the treatment of baldness. Baldness is a condition which causes the receding of the hairline and thinning of hair on the crown of the head. It’s believed to be caused by both genetic predisposition and hormones.

As of now, there is no way to slow down the balding process, and a definitive way to spark hair growth remains elusive. Many are heavily invested in finding a cure for the disease, believed to affect as many as 35 million American men. Earlier this year, Mark Black from The Trichological Society, an organization that focuses on hair sciences, explained his belief that a cure is possible within the next five years and will most definitely be here in the next 10.

“It is a matter of time before we find a cure for male pattern baldness as well as alopecia. We know so much more about hair today and how it grows,” Blake told Express.

Source: Castellana D, Paus R, Perex-Moreno M. Macrophages Contribute to the Cyclic Activation of Adult Hair Follicle Stem Cells. PLOS Biology. 2014.

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Macrophages Contribute to the Cyclic Activation of Adult Hair Follicle Stem Cells


Skin epithelial stem cells operate within a complex signaling milieu that orchestrates their lifetime regenerative properties. The question of whether and how immune cells impact on these stem cells within their niche is not well understood. Here we show that skin-resident macrophages decrease in number because of apoptosis before the onset of epithelial hair follicle stem cell activation during the murine hair cycle. This process is linked to distinct gene expression, including Wnt transcription. Interestingly, by mimicking this event through the selective induction of macrophage apoptosis in early telogen, we identify a novel involvement of macrophages in stem cell activation in vivo. Importantly, the macrophage-specific pharmacological inhibition of Wnt production delays hair follicle growth. Thus, perifollicular macrophages contribute to the activation of skin epithelial stem cells as a novel, additional cue that regulates their regenerative activity. This finding may have translational implications for skin repair, inflammatory skin diseases and cancer.

Author Summary

The cyclic life of hair follicles consists of recurring phases of growth, decay, and rest. Previous studies have identified signals that prompt a new phase of hair growth through the activation of resting hair follicle stem cells (HF-SCs). In addition to these signals, recent findings have shown that cues arising from the neighboring skin environment, in which hair follicles dwell, also participate in controlling hair follicle growth. Here we show that skin resident macrophages surround and signal to resting HF-SCs, regulating their entry into a new phase of hair follicle growth. This process involves the death and activation of a fraction of resident macrophages— resulting in Wnt ligand release —that in turn activate HF-SCs. These findings reveal additional mechanisms controlling endogenous stem cell pools that are likely to be relevant for modulating stem cell regenerative capabilities. The results provide new insights that may have implications for the development of technologies with potential applications in regeneration, aging, and cancer.

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So what does all of this mean Baldie42?

Do we know what drug was used? Can we get more information about this?


I wrote to a scientist of discovery and it is the answer: “We truly appreciate your message and interest in our research. We fully understand how complex and difficult is to suffer from hair loss, and we are committed to continue investigating in this matter.
Our current studies were performed in mice during more than five years. These results although promising, need to be further tested in mice since an over activation of skin stem cells can give rise to cancer.
Although these results can provide insights to designing therapeutic approaches, unfortunately, this will need several years to test the efficacy in humans and to evaluate their potential side effects.
Best regards,”