Plucking a high density of hairs within a small region prompts regrowth of all hairs in that area, whereas plucking more widely spaced hairs does not lead to regeneration, according to a study conducted in mice and funded in part by the NIAMS. The study, which was published in the journal Cell, suggests that hair follicles located adjacent to each other can coordinate a response to an injury in a way that widely spaced follicles cannot.
Hair follicles go through cycles of growth, destruction, rest and regeneration. Although researchers are unsure what triggers a resting follicle to regenerate, some studies have indicated that it involves signals within the follicle itself, as well as ones external to the follicle. Injury, such as plucking, can spur the process.
“Hair follicles essentially function as autonomous tissue units. Studying how they behave both as individuals and as a group helps us better understand hair loss disorders like alopecia. In addition, they may also provide insight into how other individual organs regenerate or repair themselves after injury,” said NIAMS grantee and author Cheng Ming Chuong, M.D., Ph.D., professor of pathology at the University of Southern California.
In the study, Chuong and colleagues plucked a total of 200 hairs in different configurations from the back of a mouse. When the hairs were plucked sparsely from an area more than 6 millimeters in diameter, the hairs did not regrow. However, when hairs were plucked densely from areas with diameters between 3 and 5 millimeters, the plucking triggered extensive hair regeneration—from 450 to 1,300 hairs—with some hairs growing outside of the plucked region, as well. The ability of the follicles to sense a certain threshold of lost hair and then initiate a collective response is called “quorum sensing,” a behavior that likely occurs in other tissue and organs besides the skin, the investigators suggested.
Chuong and colleagues further examined how this collective behavior among closely-situated cells was controlled. Through molecular analyses and with mathematical modeling, the researchers were able to determine the cascade of events that leads to regeneration. First, when the plucking reaches a specific threshold, the “distressed” follicles secrete a chemical called CCL2, which recruits macrophages—a type of white blood cell—to the scene. The macrophages then release a signaling molecule known as TNF-a, which directs the hair follicles in the affected region to reactivate, whether they are injured or not. The discovery of these regulatory pathways may help identify targets for therapies for alopecia and related hair loss disorders.
“What makes quorum sensing unique is that it is a coordinated behavior that occurs when a certain threshold is reached. How that threshold for triggering the regeneration response is set and regulated determines tissue stability,” said Chuong. “We hope further research will provide us with answers on how this threshold is decided. We also hope we can isolate some compounds in order to stimulate hair regeneration without having to pluck human hairs.”
This work was supported by NIAMS (grant numbers R01AR042177, R01AR047364, and R01AR060306) and by the NIH’s National Institute of General Medical Sciences (P50GM076516) and National Institute of Dental and Craniofacial Research (R01DE017449). Additional support was provided by the Taiwan National Science Council, Taipei Veterans General Hospital, National Natural Science Foundation of China, Edward Malinckrodt Jr. Foundation, California Institute of Regenerative Medicine, National Science Foundation, Top Notch University plan of CKU Taiwan, Northern Research Partnership, and the National Yang Ming University.
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Organ-level quorum sensing directs regeneration in hair stem cell populations. Chen CC, Wang L, Plikus MV, Jiang TX, Murray PJ, Ramos R, Guerrero-Juarez CF, Hughes MW, Lee OK, Shi S, Widelitz RB, Lander AD, Chuong CM. Cell. 2015 Apr 9;161(2):277-90. Doi:10.1016/j.cell.2015.02.016. PubMed PMID: 25860610
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