Hair stem cells

Some readers of this blog have expressed interest in my new hair growth which I have tentatively attributed to telomerase activation resulting from taking an astragaloside IV supplement.  This has led me to look into what recent research tells us about hair stem cells and what the implications are for impeding or reversing baldness.  I found out a lot more on the subject than I anticipated.  Here are some of the highlights.

Hair follicles

To start with, a little background on hair follicles and hair growth.  A good general source of information can be found at hairfolliclecells.com.  Basically, a hair follicle is tiny bulb-like organ that , if it remains healthy “ –keeps on producing hair throughout an individual’s life.”  Growth of a hair takes place in a cycle of the follicle in three stages: anagen – the hair growing phase which may last 2-6 years; catagen – the intermediate phase lasting 2-3 weeks where “the hair stops growing and the hair follicle shrinks and part of it starts to die(ref),” and telogen – a resting phase that lasts about three months when the hair follicle is inactive and the old hair may be shed.  Then the follicle starts the cycle over again with a new hair, pushing out the remains of the old hair if it is still there. A follicle may be reborn 10-20 times and produce that many hairs over a lifetime.

Hair follicle stem cells

Hair follicle stem cells are epithelial stem cells that divide and produce new hair follicle cells in each growth cycle.  They are found in a part of the follicle known as the bulge, though stem cells capable of generating new hair follicles may also exist elsewhere on the skin. “Interfollicular epidermal cells also retain some capacity to generate new hair follicles(ref).”  Research has shown that at least some hair stem cells are pluripotent, that is, a single stem cell can differentiate into all the multiple cell types found in a follicle.  “The rat whisker stem cells participated again in forming all the cell types needed to form the hair follicle and sebaceous glands, resulting in hair bulbs that underwent repeated normal phases of growth, rest and regeneration. The fact that the transplanted cells participate in the hair cycle over long periods of time shows that they are true multipotent stem cells and not progeniture cells(ref).” 

Actually, some hair follicle stem cells are sufficiently pluripotent that they can be induced to differentiate into multiple types of somatic cells.  “– the researchers isolated and grew a new type of multipotent adult stem cell from scalp tissue obtained from the National Institute of Health’s Cooperative Human Tissue Network.” – “The mutipotent stem cells grow as masses the investigators call hair spheres. After growing the “raw” cells from the hair spheres in different types of growth factors, the investigators were able to differentiate the stem cells into multiple lineages, including nerve cells, smooth muscle cells, and melanocytes (skin pigment cells).” –“The differentiated cells acquired lineage-specific markers and demonstrated appropriate functions in tissue culture, according to each cell type(ref).”  In fact, neural crest stem cells that live in hair follicles could possibly be used for stem cell therapy purposes in lieu of embryonic or other stem cell types(ref).  “The neural crest is a population of stem cells that migrate extensively during development and give rise to many derivatives, including most of the bone and cartilage of the head skeleton, pigment cells of the skin, and cells of the peripheral nervous system (ref).”

“Overall then, it seems that stem cells are very flexible. Stems cells form other parts of the body can form hair follicles thus triggering hair regrowth if given the correct signals. Equally, stem cells in hair follicles can also form other tissues if given the appropriate signals(ref). The implications of using hair stem cells for tissue regeneration are widespread.  “

“Engineering blood vessels for bypass surgery, promoting the formation of new blood vessels or regenerating new skin tissue using stem cells obtained from the most accessible source — hair follicles — is a real possibility,” – “The group recently produced data showing that stem cells from human hair follicles also differentiate into contractile smooth muscle cells.  “We have demonstrated that engineered blood vessels prepared with smooth muscle progenitor cells from hair follicles are capable of dilating and constricting, critical properties that make them ideal for engineering cardiovascular tissue regeneration.” – “Since smooth muscle cells comprise the muscle of numerous tissues and organs, including the bladder, abdominal cavity and gastrointestinal and respiratory tracts, this new, accessible source of cells may make possible future treatments that allow for the regeneration of these damaged organs as well(ref).”

Hair stem cells and hair growth

Stem cell division and differentiation enable a hair follicle to renew itself at the start of each growth cycle and are essential for hair growth. According to a recent report “For a new round of hair growth to begin, stem cells in the hair follicle must receive a signal to divide. In response to this signal, the hair follicle regenerates first by growing downward through the skin’s middle layer, the dermis, and then producing the specialized cells that form the hair. After a period during which the hair grows longer, stem cells stop dividing, and the hair follicle gradually retracts again. There is then a period of rest and the cycle repeats(ref).”  A small compartment at the bottom of the bulge known as the hair germ plays a role in transmitting the signal for a hair follicle to renew itself and start making a new hair. “The researchers believe, however, that toward the end of the resting phase, the hair germ gets activated to proliferate before the bulge. Moreover, the team showed that the activating signal comes from a structure known as the dermal papilla(ref).”  What are the signals? “We think that FGF7 might contribute, along with the Wnts and BMP inhibitory signals, to coax the hair germ to divide and proliferate(ref).”  In case you are wondering, FGF7 is a growth factor made by the dermal papilla; Wnts is an important protein signaling pathway; BMP is bone morphogenic protein. Wnt and BMP signaling are important for neural crest stem cell maintenance(ref), bringing us back to the probable importance of these pluripotent cells in hair follicles.

Another study reports “We’ve found that we can influence wound healing with wnts or other proteins that allow the skin to heal in a way that has less scarring and includes all the normal structures of the skin, such as hair follicles and oil glands, rather than just a scar,” explains Cotsarelis.” – “By introducing more wnt proteins to the wound, the researchers found that they could take advantage of the embryonic genes to promote hair-follicle growth, thus making skin regenerate instead of just repair. Conversely by blocking wnt proteins, they also found that they could stop the production of hair follicles in healed skin. — Increased wnt signaling doubled the number of new hair follicles(ref).”

Recent research unveiled another important property of hair follicle stem cells.  They “can divide actively and transport themselves through the skin tissue(ref).”  That means that once dividing, they are not necessarily confined to a follicle of origin. “Here we show that Lgr5+ cells comprise an actively proliferating and multipotent stem cell population able to give rise to new hair follicles and maintain all cell lineages of the hair follicle over long periods of time. Lgr5+ progeny repopulate other stem cell compartments in the hair follicle, supporting the existence of a stem or progenitor cell hierarchy. By marking Lgr5+ cells during trafficking through the lower outer root sheath, we show that these cells retain stem cell properties and contribute to hair follicle growth during the next anagen(ref).”

Finally, I found a piece of research published this month that shows a direct link between telomerase activation, Wnt signaling and epidermal (including hair) stem cell differentiation. “Either stimulation of Wnt/ -catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo,” — “These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/ -catenin signalling pathway(ref).”

All of this is to say that:

IF telomerase activation promotes the differentiation of hair stem cells (and the last citation and other research I have cited previously says it does; see the recent post Extra-telomeric benefits of telomerase –  good news for telomerase activators)

AND activated hair stem cells can wander across the skin and start new hair follicles (which the above-cited research says happens)

THEN there is a plausible basis that telomerase activation will over time lead to more and more new hair follicles and hairs appearing on the head of a previously-bald guy like me (which is happening).  Besides, my often-cited shaggy mouse story shows it works in mice.  So, why not in me?  Given that hair follicles go into renewal phase only every 2-6 years I have to be reconciled that getting a full head of hair back may take some time.