It's known that stem cells, the key players in regenerative processes in the body, play a major role in continually making new hair. Naturally, this role has caused researchers to suspect that hair stem cells are key players in causing androgenetic alopecia (AGA), or male pattern baldness, the most frequent type of hair loss among men. However, in early 2011 a group of researchers showed, surprisingly, that patients with AGA actually had a normal amount of hair stem cells in their scalps. Instead, the team found that different "progenitor cells" may actually be the cells whose fates are tied to AGA. This better understanding of the exact cell types involved may ultimately help researchers devise better therapies for treating male pattern baldness.

Adrogenetic Alopecia In order to understand how stem cells or "progenitor cells" may be involved in AGA, it's important to know how hair usually grows, and how this process is changed in AGA. At any given time, about 85 percent of the hair follicles on a person's head are in a growing phase. (Hair follicles are little cavities that go down through the dermis skin layer, and each cavity is home to a single hair. See the figure for details.) This growth phase can last two to six years for any given hair, during which time the hair grows about five inches every year (of course, there's some variation from person to person). After this growing period, the hair follicle and root shrink for one to two weeks, and during the following five to six weeks the hair stops growing. At the end of this whole process, the hair follicle re-enters the growing phase, sometimes continuing to lengthen the original hair and sometimes with a newly growing hair pushing the old one out, starting the growth cycle all over again.

Normally, the new hair will grow similarly to the previous hair. However, with AGA this isn't the case. In AGA, hair follicles get smaller over time, and consequently make smaller and smaller, eventually microscopic, hairs. How is this baldness caused? It's not that well understood; it's known that testosterone is necessary for this miniaturization, but not much else is known about what causes AGA.

Bulge Stem Cells While the ultimate cause of AGA remains thus far elusive, researchers have done a great deal of work to determine the presence and role of stem cells in normal hair follicles. Their work has lead to the present understanding that, in a hair follicle, there are stem cells that reside in a small compartment called the "bulge" (as shown in the figure). These stem cells can turn into nearly all of the different cell types found in the hair follicle. They're intimately involved in the hair follicle life-cycle; if these stem cells are destroyed, so is the hair follicle.

A study by George Cotsarelis and colleagues at the University of Pennsylvania School of Medicine, published in February of 2011 in The Journal of Clinical Investigation, set out to resolve whether these bulge stem cells play a key role in AGA. To do this, the team took samples of skin cells from the heads of people with AGA, and compared samples from areas that were bald to areas that were haired (non-bald). What did they "compare" exactly? To figure out what kinds of cells were present in their samples, the researchers looked at what proteins were in the samples. Certain cells make certain proteins. For example, researchers can identify if their sample has stem cells from the "bulge" by looking for the presence of certain proteins known to be made only by those cells. After all of this preparation, the researchers found that, surprisingly, the percentage of bulge stem cells was the same in both the bald and haired samples. The presence of the bulge stem cells isn't enough to prevent hair follicle miniaturization in AGA.

Progenitor Hair Cells With their main suspect, the bulge stem cells, released from suspicion due to the new evidence, the researchers realized that other cellular players may be the real culprits behind male pattern baldness. Their suspicions quickly shifted to some "progenitor cells." < a href="http://en.wikipedia.org/wiki/Progenitor_cells">Progenitor cells are like stem cells in that they can turn into several different types of cells, but, unlike stem cells, progenitors can divide and multiply a relatively limited number of times (stem cells can replicate many times); progenitors have a much more limited lifespan.

In the hair follicle, the bulge stem cells are known to give rise to different groups of hair progenitor cells. Usually the progenitors travel to the bottom of the hair follicle when a new hair starts to grow, giving rise to the cells necessary for the new hair and acting as a kind of "middle man" between the stem cells and the final desired cell types.

To determine whether progenitor cells were connected with AGA, the researchers started looking for the presence of other proteins in their bald and haired cell samples, proteins known to be made by different groups of cells in hair follicles. Sure enough, they found a connection; they discovered a group of cells that was present in the haired samples but absent in the bald samples. Based on the activity level and size of these cells, the researchers think this population of cells could indeed be a group of progenitors. Furthermore, by looking at what other proteins these progenitors made, the researchers were able to narrow down their location within the follicle; they live in the bulge, as well as an area near the bulge known to house progenitors. Altogether, it's very likely that these potential culprits are progenitors derived from the bulge stem cells. Importantly, the team also showed that these progenitors could produce all of the cell lineages found in a hair follicle, an indication that their absence could certainly lead to problems with hair growth. Overall, this work cataloged a group of progenitor cells that had not been previously identified and found that these novel cells likely have a key role in the onset of AGA, male pattern baldness.

strong>The Potential of the Progenitors These relatively recent findings reported by Cotsarelis and colleagues not only help us better understand how baldness in AGA may be caused, but also how AGA may be treated. The authors hypothesize that in AGA, bulge stem cells that have somehow become inactivated may result in a loss of the essential progenitor cell populations. Because the novel progenitors were shown in their report to be able to generate a number of important hair follicle cell lineages, such a loss of their numbers may lead to the miniaturization of the hair follicle, a hallmark sign of AGA. But because there are still bulge stem cells, which can make new progenitor cells, present in all of the hair follicles of patients with AGA, it suggests that the AGA condition may be reversible. By better understanding these complex and varied progenitor cell populations, researchers may be able to determine what signals are necessary to coax the remaining bulge stem cells to become the necessary progenitor cells for hair growth, and consequently a promising cellular treatment for AGA may be waiting just over the horizon.

This article originally appeared in Teisha Rowland's "Biology Bytes" column at The Santa Barbara Independent as the article "Hair So New" and is reproduced here with the author's permission.

For more on hair stem cells and progenitors, see Teisha Rowland's All Things Stem Cell post on Progenitor Hair Populations are Key to Understanding Male Pattern Baldness. For more on stem cells in general, see The National Institute of Health's Stem Cell FAQs, other Biology Bytes articles, including one on The Stem Cell Family, or, for a visual explanation of terms used, see All Things Stem Cell's Visual Stem Cell Glossary.

Teisha Rowland, PhD, was a science writer for The Santa Barbara Independent, where she was author of the column "Biology Bytes." Teisha maintains a blog at All Things Stem Cell and, since receiving her PhD in molecular, cellular, and developmental biology at the University of California at Santa Barbara, where she studied stem cells, she has become an educational science writer for Science Buddies. Send any column ideas, questions, or comments to her at Teisha@AllThingsStemCell.com.