A: Many scientists feel that adult stem cells house the answer to cloning (regeneration) of hair follicles. One of the problems of hair cloning, however, is that the cells, once duplicated, “forget” that they are hair follicle cells.

It has recently been discovered that the Lgr5 gene, located in stem cells, appears to contain the “global marker” present in all adult hair follicles. If Lgr5 gene is the “calling card” of the cell, it may carry the cell lineage and shoulder the responsibility of signaling to surrounding stem cells what they are actually supposed to do as they multiply.

Recent experiments have shown that these Lgr5 cells maintain the cells ability to differentiate as hair follicles after many generations of being multiplied in the test tube and, therefore, have the potential of serving as the building blocks of entire new hair follicles. The successful exploitation of this gene would eliminate a major barrier to cloning hair.

Reference
Haegebarth A, Clevers H: Wnt signaling, lgr5, and stem cells in the intestine and skin. Am J Pathol. 2009 Mar; 174(3):715-21.

For more on how hair cloning works, visit the Bernstein Medical – Center for Hair Restoration page on hair cloning.

A: Cloning generally refers to the multiplication of fetal stem cells or embryonic tissues. “Hair cloning”, as the term is generally used, involves the multiplication of adult tissue cells that are used to induce the formation of new hair, so the term is not exactly accurate.

“Hair multiplication” refers to the multiplication of adult hair structures. This model is not actively being pursued since the hair follicle is too complex to be simply cultured in a tube. Instead individual cells called fibroblasts are removed from the scalp multiplied in tissue culture and then these are injected back into the scalp in the hope that they will induce intact follicles to form.

“Follicular neogeneis” is probably the best of these terms, as it describes the formation of new follicles derived from inducer cells that are cultured and then injected into the scalp. It is the preferred term of Ken Washenik at Aderans. Interctyex uses the term “follicular cell regeneration” for its technology.

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.