Anagen Inducer - Bernstein Medical - Center for Hair Restoration
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Could a hormone that plays a critical role in red blood cell production also play a critical role in hair follicle production? According to a 2010 research report published in the Journal of Dermatological Science, this may be the case.

Erythropoietin Implicated In Hair Growth Regulation

The hormone in question is called Erythropoietin (EPO). It is produced in the kidneys in order to regulate red blood cell production. Recent studies have shown that EPO is also produced in a structure that surrounds and protects a hair follicle, the outer root sheath (ORS). Moreover, other studies have found that the EOP secreted by the ORS seems to target dermal papilla (DP) cells. DP cells play a critical role in regulating hair growth.

Because of these results, researchers have speculated that EPO may affect hair growth by acting on DP cells, but no direct evidence for this had ever been found – until now.

Evidence That EPO Affects Hair Growth in Vitro (Cell Cultures)

Strong evidence of EPO’s direct involvement in hair growth would be the discovery of EPO receptor sites (EPOR) on DP cells and a clear mechanism of how EPO affects changes in a DP cell (called cell signaling); this is exactly what researchers in the Republic of Korea ((Kang BM, Shin SH, Kwack MH, Shin H, Oh JW, Kim J, Moon C, Moon C, Kim JC, Kim MK, Sung YK. Erythropoietin promotes hair shaft growth in cultured human hair follicles and modulates hair growth in mice. J Dermatol Sci. 2010 Aug;59(2):86-90. doi: 10.1016/j.jdermsci.2010.04.015. Epub 2010 May 19.)) have found. Not only did they find direct evidence of EPO receptive sites but they also discovered the critical cell signaling mechanism: phosphorylated EPOR signaling pathway mediators.

In addition to discovering the signaling mechanism, they also showed using cell cultures that EPO causes both dermal papilla to proliferate and hair shafts of human hair follicles to elongate.

While the effects of EPO on DP and hair follicles were compelling, they only occurred in vitro (in cell cultures outside the body) and it is known that cells cultured on a flat surface behave significantly differently than cells that exist in situ, inside the organism (see Higgins and Christiano, Regenerative Medicine And Hair Loss: How Hair Follicle Culture Has Advanced Our Understanding Of Treatment Options For Androgenetic Alopecia).

Evidence That EPO Affects Hair Growth In Situ (In The Body)

In order to better answer the questions of whether and how EPO might directly affect hair growth in situ, the Korean researchers implanted EPO treated DP cells into mice and found that these treated cells not only moved hair follicles from their resting (telogen) phase into an active hair growth (anagen) phase but also prolonged a follicle’s active growth phase.

This is a significant finding since one of the mechanisms of male pattern baldness is DHT susceptible hair follicles entering into progressively longer periods of a telogen (resting) phase relative to an anagen (hair growth) phase. EPO, having the opposite effect on hair follicles, opens the door to treating this type of hair loss with existing EPO analogs and/or developing new erythropoietin biopharmaceuticals.

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Q: I know that both Aderans and Intercytex are doing research with cloning hair. Is there any difference in their approaches?

A: Aderans is using the “two-cell” approach. They feel that the best way to produce viable hair follicles is to use a combination of inducer cells and responder cells. Each would be multiplied separately and then injected together into the skin. The inducer cells are follicular fibroblasts and lie at the base of the hair follicle. The responder cells are keratinocytes. They feel that the combination of cells will have the best chance of producing clinically useful hair.

Intercytex prefers a one-cell approach. Their researchers feel that when the cultured inducer fibroblasts are injected into the skin there will be enough existing cells in the skin to produce a cosmetically viable hair. In their experimentation, Intercytex uses a new animal model, termed the “flap graft” model, that involves the implantation of cultured dermal papilla cells with keratinocytes placed under a flap on the back of hairless mice. Later the flap is exteriorized (turned over), allowing the hair to grow normally. Exactly how this will be applied to clinical use in humans is not clear.

A completely different view is held Dr. Ralf Paus at the University of Luebeck in Germany. He feels that there are already enough stem cells in the bald scalp and that the key to hair re-growth is to target key elements in the hair cycle. He feels that topically applied inhibitors of catagen (the resting phase of the hair cycle), exogen (the formation of an empty hair follicle), or inhibitors of the terminal-to-vellus transformation (the process of a hair shrinking in size under the influence of DHT and referred to as miniaturization) will the most effective way to go.

Finasteride and dutasteride are drugs that work in this way, but are clearly not very effective in stimulating new growth. He also feels that an anagen inducer, along the lines of a minoxidil-type medication has a better chance of success then the stem cell targeting strategies described above. In these cases one would, in a sense, rejuvenate dormant hair follicles rather than induce new ones to grow.

Read about Hair Cloning Methods

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