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The study below has been cited a few times by various people on hairloss sites over the last couple of years, but I've read the whole thing, and I want to present some of the interesting details from it. First of all, here's the abstract:
J Am Acad Dermatol. 2003 May;48(5):752-9.
"Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice"
Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.
"Human hair follicles were grafted onto 2 strains of immunodeficient mice to compare the regeneration potential of vellus (miniaturized, balding) and terminal (hairy, nonbalding) follicles from males and a female exhibiting pattern baldness. Each mouse had transplants of both types of follicles from a single donor for direct comparison. Grafted follicles from 2 male donors resulted in nonsignificant differences in mean length (52 mm vs 54 mm) and mean diameter (99 microm vs 93 microm) at 22 weeks for hairs originating from balding and hairy scalp, respectively, corresponding to 400% versus 62% of the mean pretransplantation diameters. Follicles from the female donor transplanted to several mice also resulted in nonsignificant differences in length (43 mm vs 37 mm) for hairs from balding and hairy scalp, respectively, during a period of 22 weeks. The mean diameter of the originally vellus hairs increased 3-fold, whereas the terminal hairs plateaued at approximately 50% of pretransplantation diameter, resulting in a final balding hair volume double that of the nonbalding hairs. This report shows that miniaturized hair follicles of pattern alopecia can quickly regenerate once removed from the human scalp and can grow as well as or better than terminal follicles from the same individual."
The abstract gives the salient points: they found that fine vellus hairs from balding human scalps had an EXCEPTIONAL ability to regenerate, when transplanted onto test mice that had severe immune deficiency (they use those for transplant experiments so that the mice don't suffer rejection of the foreign tissue). In fact, after about 5 to 6 months, transplanted follicles with vellus hairs regrew to the same size as the transplanted terminal hairs in one set of mice, and actually grew LARGER than the terminal hairs in another set of mice (for which phenomenon they don't yet have any explanation)! Here's an extended excerpt from the Discussion section at the end in which they speculate about the various implications of their findings:
"...The phenomenon occurring in the xenograft experiments reported here is quite different and dramatic: hypotrophic anagen and telogen hairs from balding scalp exhibiting only vellus hairs in situ regenerate very quickly. By six months, the ratio of the diameters of grafted to pretransplant vellus hairs exceeds 3:1 (Fig 3). Histologic examination of post-transplantation follicles from balding scalp also shows fully developed anagen follicles at six months (Fig 2). The regeneration of vellus follicles occurs just as quickly on male as on female mice (data not shown); this suggests that a factor or factors other than androgen withdrawal may be involved but does not necessarily rule out that differences in androgen levels, availablity, or both between human beings and mice account in part or entirely for the rapid vellus-to-terminal transformation of balding follicles. For instance, the activity of the 5a-R enzyme(s) may be greatly reduced or absent in the transplanted follicles, thereby, limiting exposure of the follicles to DHT. The accelerated transformation of vellus follicles on immunodeficient mice might correspond to responses seen in balding men treated with oral finasteride who are exceptionally good responders. However, in our clinical experience, females with Androgenetic Alopecia, including the female in study II, frequently have normal androgen and androgen-binding globulin levels for their age and sex. It is difficult to argue that lower systemic androgen levels in the female mouse environment (or higher in the male mice) causes the rapid regeneration of vellus hair follicles from the human female. Therefore, the existence of an inhibitor factor other than androgens, particularly in women showing diffuse/pattern alopecia, that is lacking in the nude mouse seems plausible. This could be some other steroid, hormone, cytokine, neuropeptide, or an immunologically related factor."
I think that last part about the "immunologically related factor" is an understatement! :wink: After reading this paper, it now seems likely that the immune system is an even bigger factor in male pattern baldness than was previously thought. I personally had always assumed that the putative attack on hair follicles by the immune system was something that happens relatively late in the game, but this study is awfully compelling. But oddly enough, you see very little about this aspect of balding in the medical literature. Dr. Proctor, OTOH, has talked about it for years on alt.baldspot.
So what really is the point of bringing this up in the first place, this issue "Of Mice and Men"?? :wink: Well, I think it can be a source of great hope for all of us! It proves that there exists the POTENTIAL for our poor follicles to regenerate completely all on their own, if only we can figure out how to let that happen. It appears that we may not have to wait for far-off and possibly risky genetic treatments, or puzzle-out all those very complex mesenchymal-epithelial interactions (HM, in other words), or depend on other high-tech treatments. We may find simpler, safer ways to do it, with the additional clues provided by this fascinating study.
Bryan
J Am Acad Dermatol. 2003 May;48(5):752-9.
"Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice"
Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.
"Human hair follicles were grafted onto 2 strains of immunodeficient mice to compare the regeneration potential of vellus (miniaturized, balding) and terminal (hairy, nonbalding) follicles from males and a female exhibiting pattern baldness. Each mouse had transplants of both types of follicles from a single donor for direct comparison. Grafted follicles from 2 male donors resulted in nonsignificant differences in mean length (52 mm vs 54 mm) and mean diameter (99 microm vs 93 microm) at 22 weeks for hairs originating from balding and hairy scalp, respectively, corresponding to 400% versus 62% of the mean pretransplantation diameters. Follicles from the female donor transplanted to several mice also resulted in nonsignificant differences in length (43 mm vs 37 mm) for hairs from balding and hairy scalp, respectively, during a period of 22 weeks. The mean diameter of the originally vellus hairs increased 3-fold, whereas the terminal hairs plateaued at approximately 50% of pretransplantation diameter, resulting in a final balding hair volume double that of the nonbalding hairs. This report shows that miniaturized hair follicles of pattern alopecia can quickly regenerate once removed from the human scalp and can grow as well as or better than terminal follicles from the same individual."
The abstract gives the salient points: they found that fine vellus hairs from balding human scalps had an EXCEPTIONAL ability to regenerate, when transplanted onto test mice that had severe immune deficiency (they use those for transplant experiments so that the mice don't suffer rejection of the foreign tissue). In fact, after about 5 to 6 months, transplanted follicles with vellus hairs regrew to the same size as the transplanted terminal hairs in one set of mice, and actually grew LARGER than the terminal hairs in another set of mice (for which phenomenon they don't yet have any explanation)! Here's an extended excerpt from the Discussion section at the end in which they speculate about the various implications of their findings:
"...The phenomenon occurring in the xenograft experiments reported here is quite different and dramatic: hypotrophic anagen and telogen hairs from balding scalp exhibiting only vellus hairs in situ regenerate very quickly. By six months, the ratio of the diameters of grafted to pretransplant vellus hairs exceeds 3:1 (Fig 3). Histologic examination of post-transplantation follicles from balding scalp also shows fully developed anagen follicles at six months (Fig 2). The regeneration of vellus follicles occurs just as quickly on male as on female mice (data not shown); this suggests that a factor or factors other than androgen withdrawal may be involved but does not necessarily rule out that differences in androgen levels, availablity, or both between human beings and mice account in part or entirely for the rapid vellus-to-terminal transformation of balding follicles. For instance, the activity of the 5a-R enzyme(s) may be greatly reduced or absent in the transplanted follicles, thereby, limiting exposure of the follicles to DHT. The accelerated transformation of vellus follicles on immunodeficient mice might correspond to responses seen in balding men treated with oral finasteride who are exceptionally good responders. However, in our clinical experience, females with Androgenetic Alopecia, including the female in study II, frequently have normal androgen and androgen-binding globulin levels for their age and sex. It is difficult to argue that lower systemic androgen levels in the female mouse environment (or higher in the male mice) causes the rapid regeneration of vellus hair follicles from the human female. Therefore, the existence of an inhibitor factor other than androgens, particularly in women showing diffuse/pattern alopecia, that is lacking in the nude mouse seems plausible. This could be some other steroid, hormone, cytokine, neuropeptide, or an immunologically related factor."
I think that last part about the "immunologically related factor" is an understatement! :wink: After reading this paper, it now seems likely that the immune system is an even bigger factor in male pattern baldness than was previously thought. I personally had always assumed that the putative attack on hair follicles by the immune system was something that happens relatively late in the game, but this study is awfully compelling. But oddly enough, you see very little about this aspect of balding in the medical literature. Dr. Proctor, OTOH, has talked about it for years on alt.baldspot.
So what really is the point of bringing this up in the first place, this issue "Of Mice and Men"?? :wink: Well, I think it can be a source of great hope for all of us! It proves that there exists the POTENTIAL for our poor follicles to regenerate completely all on their own, if only we can figure out how to let that happen. It appears that we may not have to wait for far-off and possibly risky genetic treatments, or puzzle-out all those very complex mesenchymal-epithelial interactions (HM, in other words), or depend on other high-tech treatments. We may find simpler, safer ways to do it, with the additional clues provided by this fascinating study.
Bryan
