Hair Loss - On the "donor dominance" of transplanted hair follicles
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On the "donor dominance" of transplanted hair follicles (All Topicals & Shampoos)

posted by Dr. Yechiel, 20.04.2009, 19:29

Hello Bryan,

Two of the articles you referenced are very old articles and have not yet been made available for online viewing, so there is a delay while I order them from the library and wait to receive them. Today I received the 1959 Orentreich paper. When I receive the 1979 Nordstrom article I will see if there is anything there which contradicts the notions that the acceptor tissue is relevant to a successful transplantation or that miniaturized follicles can recover.

As for the 1959 Orentreich paper, he actually makes a clear distinction between donor/acceptor tissue and follicles. He claims that donor dominance is reflected in the “tissue” and he states the necessity for the tissue to be at full thickness for a viable transplant. As for the follicles themselves, he states that the article “suggests” that MPB should be attributed to the follicles themselves. In fact, the most you can derive from this article is that it does not contradict the possibility that follicles may be preset for MPB, but the article by no means suggests that. Dr. Orentreich (still active as of 2008) is quite a remarkable guy and is also heavily involved with Clinique. His son is also involved with Clinique as their guiding dermatologist and their concepts about hair growth appear to be affecting much of the concepts involved in formulation and commercialization of hair and scalp products. In my opinion his 2003 article is important because it appears to contradict some of the conclusions in his 1959 article and some important concepts about hairloss which he advocated for a long time.

When you say that you can't believe that the surrounding skin tissue in large grafts really has anything to do with balding, I take it that you don’t mean it in the extreme that the surrounding tissue is completely irrelevant to hair growth, but rather as an expression which carries little weight for the role of the surrounding tissue. So, the question is to what degree the surrounding tissue is relevant or irrelevant. I believe that the degree of relevancy of the surrounding tissue is critical and I believe that it is clearly illustrated in the 2003 Krajcik-Orentreich article where human hairs were individually transplanted into mouse skin. High relevancy of the surrounding tissue is actually backed up by resolving the apparent contradiction between the Nordstrom article (based on your summary of it) and the 2003 Krajcik-Orentreich, which I will discuss below.

Bear in mind that Orentreich's 1959 paper with his theory of “donor’s dominance” was published at a time when knowledge about genetic factors in general and environmental factors in particular was not very advanced. In the 1950s, scientists were still struggling with theories about the structure of cell membranes and the structure of DNA and knew almost nothing about genes. The development in studies of environmental factors in biology is recent and even nowadays it is only at the beginning of the road. I would rephrase the older terminology “donor’s dominance” versus “acceptor’s dominance” into a different structure: “genetic relevancy” versus “environmental relevancy”. On the basis of this phrasing, I would state that the genetic makeup (say, of a follicle) will determine its potential (the color of the hair, the maximum thickness and length of the hair, etc.) while the environmental factors will determine how much of the genetic potential will be expressed in reality and which aspects will be fully developed or under developed. When you look at hair transplantation with this view in mind, the tissue around the transplanted follicle (also from the donor) acts as an environmental support for the follicle itself. Therefore, the question of whether the follicle is surrounded by donor’s tissue (as in large skin grafts) or by the acceptor’s tissue (individual follicle grafts which will eventually be surrounded by the host tissue) becomes very critical. We know that a tree which can grow 100 feet tall can be made into a 1-foot bonsai tree because it is subjected to environmental limitations which prevent it from reaching its full potential as described in its genetic makeup; there are many other examples. Interaction is another level which relates to both genetic and environmental factors via feedback of hormones, growth factors, innervations, blood supply, and just name it, which depends very much on the environment (surrounding tissue) but also on the ability of the follicle itself to register such signals, assimilate them, receive adequate nutrition, physical space, and send feedback to the environment to produce more of some kinds of molecules or less of another kind of molecules. This is an area where complexity is vast and it also requires the surrounding tissue to comply and reciprocate with signals or back-signals sent by the follicle. If there is a blockage or a rupture where signals are blocked or flow is unregulated, or if there are mechanical/structural changes of the surrounding tissue (thinning of the skin in which space the follicle is embedded), the follicle will begin to experience less than perfect conditions which will perpetuate and deteriorate with every feedback cycle until the imperfection is visible to the eye in the form of a miniaturized follicle and with loss of some of its functions including the ability to grow full-size hairs.

If the second article you mentioned - the 1979 Nordstrom article - is as you summarized, that follicles from a bald area which were planted in the arm of the same person (no concern about rejection) remain bald and on the other hand in the 2003 Krajcik-Orentreich the individual follicles (individually trimmed from already tiny-2mm scalp sections) succeeded to grow and to develop into nice terminal hair in the skin of a mouse which is very different from the follicle’s origin (human scalp), I would say that it strongly indicates that there is a fundamental difference between large skin grafts and individual follicles. We can also look within the surrounding tissue for reasons of better or worse hair growth and assume for most cases that the follicles themselves are recoverable. The difference between the results in the 2 articles is in the environment or immediate tissue which surrounds the follicle. You are right that normal follicles in that experiment expressed thinner than usual hairs but the miniaturized follicles actually expressed larger and well-developed terminal hairs as compared to their performance on the original human scalp. The other interesting issue is that both normal and miniaturized follicles grew hair of similar thickness and length. The miniaturized follicles recovered to the same level as the normal follicles retreated. So why don’t they grow like perfect hair on a perfect scalp? Since mouse skin may not be the ideal environment for growing human hair the normal follicles did not perform as well as they did in the more ideal human scalp, while the mouse skin was still more accommodating to the miniaturized follicles than their original human scalp. As mentioned above, environment determines how much of the genetic potential will be realized. In an experiment where normal follicles were grown in culture, they developed for about 11-17 days before they stopped. So, mouse skin is more supportive of human hair follicles than tissue culture, and maybe if a similar experiment can be done on pig skin (which is very similar to human skin) or on human skin, the environmental support conditions might be even better. If several different animals or other systems which support normal follicle growth will also support miniaturized follicle recovery to the extent of normal follicles, but will differ in the final results from each other (each animal model or system will allow different hair length, thickness, etc., but will not discriminate between individual follicles, normal or miniaturized), it will settle the follicle recovery issue and will allow acceptor models for viable transplant which can be further tested for effects of different chemical on various growth parameters. However, one thing is clear from the 2003 Krajcik-Orentreich article: miniaturized follicles recovered to the extend that they started to grow normal hairs (indeed, under less than perfect conditions, but growing nevertheless, which means that they are recoverable).

In my previous response I posed the question of whether drugs which are meant to attenuate the immune system (like after kidney transplant) grow hair. Well, indeed they do and I was hoping for such comments. Cyclosporine, an immune suppressor is known for its nasty side-effects on kidneys and liver. In some individuals it causes hair growth all over the body and the scalp (hirsutism) for a certain time period. However, it grows hair also on nude mice which have defective immune systems, which indicates that the hair growth mechanism is not due to the suppression of the immune system but via another molecular mechanism which is actually under advanced study. It is not to say that the immune system is irrelevant to hairloss, quite the contrary. It is to say that the term “immune system” is too large for this purpose. Inflammation can contribute to scalp scarring and related hairloss. There may be other relevant immunodeficiencies but a direct connection between the immune system and hairloss is still to be demonstrated.

Thank you again for your input.

Elishalom Yechiel, Ph.D.
President
Elsom Research Co., Inc.
email: innovation@elsomresearch.com
voice: 210.493.5225
paper mail: 4510 Black Hickory Woods, San Antonio, TX, USA, 78249
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Dr. Yechiel is located in [NA] and he is available to meet: NO

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