Whatever Happened To All The Replicel/shiseido Hype?

[hanginginthewire]

Or alternatively, to "cure" male pattern hair loss, you would have to study in detail in ways that no one has ever done before why some men's scalps do not upregulate their androgen sensitivity genes in response to galeal tension and mechanical stress, and try to develop a therapy that somehow recreates that resistance to galeal mechanical stress in balding men.

Probably what happens in men who are resistant to male pattern hair loss is some combination of the following:

• There is something unique about their hair follicle genetics, where the androgenic sensitivity genes that are upregulated in balding men due to galeal stress are not expressed in response to the same mechanical pressures.
• There is something unique about the connective tissue that links their hair follicles to the galea that prevents mechanical stress from being transduced to the hair follicle.

But both possibilities would not be easily replicated in non-balding men. These are likely genetically programmed differences like eye color or height. In hundreds of years, perhaps the genetics responsible will be understood and we can program future children to be free from these problems. But we cannot change the fundamental genetics of our hair follicles or the basic mechanical features of our scalp dermis in the way that we would need with current technology.

So again, we must approach the problem from a more practical standpoint of intervening in the inflammatory cascade at the varying levels we have the capacity to. Fighting hair loss will always then be a lifelong struggle, and those of us who are prone to it (ie. most men) must do our best to find the agents we can tolerate best and work most effectively for us.

Alternatively, a "cure" could be developed through technologies of hair multiplication, where if you have infinite follicles and infinite time and money, you can just keep getting tens of thousands of hair transplants every 10-20 years or so. But the scalp fibrosis and scarring from doing so would be prohibitive, as well as risks of these stem cell therapies generating cancer, so even if money was not an issue, this would not be wise without still using an ongoing conventional hair loss treatment to stop the loss of the new hairs once they are placed.

This is really interesting but boy oh boy is it depressing. I’ve really come to hate that word, “androgen.” Also, Norwood. Inflammation. Cascade.

Anyway, thanks for all the informative posts. You’re truly an asset to the forum.

 

[hanginginthewire]

Also let’s copy and paste these posts to the Brotzu thread. Talk about throwing a bucket of cold water on the delusion-apalooza that is occurring on the daily over there.

 

[sunchyme1]

i hope daro makes ideal's dick turn into vagina so hes forced to stay here for another ten years or so trying to figure out how to reverse it. and in between can help the rest of us!

 

[IdealForehead]

i hope daro makes ideal's dick turn into vagina so hes forced to stay here for another ten years or so trying to figure out to reverse it. and in between can help the rest of us!

Hahahaha

 

[NorwoodGuardian]

Some idiots always pretend to be an expert but in fact they are just bro-scientists. Do you think that what you think is not considered or noticed by Tsuiji? I don't even waste my time to read your whole passage, sorry…

 

[sunchyme1]

Some idiots always pretend to be an expert but in fact they are just bro-scientists. Do you think that what you think is not considered or noticed by Tsuiji? I don't even waste my time to read your whole passage, sorry…

lol u hating bro?

 

[IdealForehead]

Some idiots always pretend to be an expert but in fact they are just bro-scientists. Do you think that what you think is not considered or noticed by Tsuiji? I don't even waste my time to read your whole passage, sorry…

So you:

- Didn't read my posts
- Have no idea what my knowledge level is or academic qualifications are
- Didn't read the peer-reviewed article I linked explaining all the science behind what I said

But think you are qualified to dismiss it?

 

[NorwoodGuardian]

So you:

- Didn't read my posts
- Have no idea what my knowledge level is or academic qualifications are
- Didn't read the peer-reviewed article I linked explaining all the science behind what I said

But think you are qualified to dismiss it?

View attachment 84237

I don't need to read your posts and know your knowledge level in order to conclude that you are much much less knowledgeable than Tsuiji and I think most of the baldies here will trust Tsuiji more than you. You think who you are?

 

[IdealForehead]

I don't need to read your posts and know your knowledge level in order to conclude that you are much much less knowledgeable than Tsuiji and I think most of the baldies here will trust Tsuiji more than you. You think who you are?

I am not interested in sharing anything personal about myself. If you are someone who makes decisions on faith and belief rather than objective scientific information, I won't have much to say to you.

But I will comment this much further.

The article that I linked summarizing this mechanism of hair loss was published in February 2018 (ie. 2 months ago). One of the most critical findings that underlies it was published in 2015. Tsuji started working on his approach to treating hair loss at least 7 years ago, and he has followed along that track steadily since.

You asked if Tsuji isn't surely aware of this newer research. I don't know if he is aware of it or not. However, at this stage, it is likely that even the absolute knowledge of this new research would not change anything for him in the future. He is being paid a hefty salary at this point to continue development of his current treatment method. It is the culmination of many years of research for him. Furthermore, even if this does not "cure" hair loss, it can still become a useful therapy if it helps to rejuvenate hair follicles, stimulate some neogenesis, or impart even temporary androgen immunity to hair.

So whether Tsuji is aware of this new research or not is quite irrelevant. As is who you choose to trust. Trust has nothing to do with scientific truth. That is the only thing I'm personally interested in.

 

[Feelsbadman.jpg]

Furthermore, even if this does not "cure" hair loss, it can still become a useful therapy if it helps to rejuvenate hair follicles, stimulate some neogenesis, or impart even temporary androgen immunity to hair.

I don't think you understand what Tsuji is doing based off of this. What you are describing is in line more with RCH-01 although the androgen resistant effects do not appear to be temporary as they held up after 5 years as per the phase I study results. This thread is about Shiseido and RCH-01. Not Tsuji.

Tsuji is working on replicating donor hair follicles to create unlimited donor hair for hair transplant. Hair transplants currently work by and large with their only limitation being donor hair which Tsuji is working to solve. So I am not really sure what it is that you are arguing. Tsuji won't work because hair transplants don't work....? Right....

 

[IdealForehead]

I don't think you understand what Tsuji is doing based off of this. What you are describing is in line more with RCH-01 although the androgen resistant effects do not appear to be temporary as they held up after 5 years as per the phase I study results. This thread is about Shiseido and RCH-01. Not Tsuji.

Tsuji is working on replicating donor hair follicles to create unlimited donor hair for hair transplant. Hair transplants currently work by and large with their only limitation being donor hair which Tsuji is working to solve. So I am not really sure what it is that you are arguing. Tsuji won't work because hair transplants don't work....? Right....

Hair transplants are explained to work as follows:

Explaining donor hair transplant survival rates

Hair transplants (hair transplant) involve the surgical transfer of non-Androgenetic Alopecia-affected scalp hair follicles from the sides and backs of the scalp to Androgenetic Alopecia-affected tissues. hair transplant hair count survival rates can exceed 90% one year after surgery [84]. If calcification and fibrosis are the rate-limiting factors to Androgenetic Alopecia recovery, then why do hair transplant donor hairs not miniaturize? This is answered with the model.

hair transplant surgeries transplant more than just the hair follicle itself. Follicular unit grafts(FUG) procedures transplant “1–4 terminal hair follicles, one (or rarely two) vellus follicles, associated sebaceous lobules, insertion of erector pili muscle, [and the] perifollicular neurovascular network” [85]. Follicular unit extraction (FUE) procedures target singular follicles more specifically, typically with a 1 mm punch [86]. In either case, tissues surrounding each donor hair follicle are also transplanted.

hair transplant donor tissue sites are not above the GA, and are therefore not under the same chronic tension before their transplantation – implying an absence of perifollicular fibrosis or dermal sheath thickening present in Androgenetic Alopecia-affected tissues. Androgenetic Alopecia progression is a decades-long process. If most transplanted donor hair follicles survive one year after hair transplantation, it’s likely these hair transplant follicles have not yet had enough time under tension exposure for fibrosis or dermal sheath thickening onset, and thereby hair follicle miniaturization.

One study comparing characteristics of transplanted hairs to and from legs and balding scalps found that “the recipient site influences the growth characteristics of transplanted hairs” [87], with “the thickness of the epidermis, dermis, or subcutaneous tissue, blood supply, or other factors play[ing] a role in survival and growth rate differences.” Another team showed that balding human vellus hair regenerates just as well – and sometimes better – on immunodeficient mice versus terminal human hair [88]. This implies that tissue environment surrounding hair follicles impacts follicle functionality, and that a rate-limiting recovery factor exists in Androgenetic Alopecia tissues. Therefore, hair transplant success fits in-line with the model, and decades-long studies are still needed to determine the true fate of transplanted donor hairs.

https://www.sciencedirect.com/science/article/pii/S0306987717310411#b0285
​

I do not think we can be certain of what product (if any) will be manifested from Tsuji's work. Many researchers can set out to accomplish one thing and accomplish something else instead. I have personally never been optimistic that Tsuji will be able to create a mass approach to hair cloning, especially not within 18 months of today, as he has claimed he would. I said 6 months ago this target was unrealistic, and I still believe it is. Maybe by 2025? Maybe longer? I don't know. So I'm not sure what his company will "release" in 2020, if anything.

Absolutely if Tsuji can be successful at replicating hair follicles this will be incredibly helpful for restoring hair in advanced hair loss. However, you might still have to take finasteride after the procedure, unless you want to eventually get another procedure in another 10-20 years, after the mechanical stresses have re-exerted themselves and the new hair again begins to miniaturize and fall out.

 

[Feelsbadman.jpg]

That would be interesting and it is unknown whether that would work but we can develop an informed perspective by considering the facts as we know them.

In theory the holy grail of hair loss treatment is not actually to do hair cloning and then transplant those hairs one by one, but rather to grow an entire lawn of healthy new scalp and hair and transplant that as one big unit. ie. If you can grow an entire lawn of 20 cm x 30 cm new scalp in a lab with perfect hair density, you can very easily then "cut" this lawn into a nice shape, excise the balding scalp completely, and replace it with the new lawn.

This could provide absolute perfect density with only a scar to deal with around the edges (which could be treated with lasers or camouflaged with small transplants).

But what would happen if you actually did this? Almost certainly, unfortunately, Androgenetic Alopecia would start again in time, as the dermis and connective tissue under the new scalp lawn would inevitably fuse to the galea, just like the natural scalp did. Then the same mechanical stresses from the galea would re-exert themselves over the years, upregulating androgen sensitivity genes in the hairs that overlie the galea, and eventually leading to the miniaturization and demise of those hairs in turn.

So unfortunately that approach would likely not solve the problem either. Also sorry, @sunchyme1 , but what this suggests is this is basically an unsolvable problem in a permanent sense and no "one time cure" will exist in our lifetime. We can hope for new anti-androgens, new stem cell therapies, etc. But hair loss will always be a lifelong battle as long as you choose to fight it.

And yet transplanting follices one by one does work....... People get hair transplants and the results last for decades....... I'm not sure why you are trying to complicate things with talk of scalping people and suturing on a new scalp with hair back on.... This seems rather absurd.

Can you please explain to me why do hair transplants currently work and produce long lasting results?

 

[NorwoodGuardian]

I don't think you understand what Tsuji is doing based off of this. What you are describing is in line more with RCH-01 although the androgen resistant effects do not appear to be temporary as they held up after 5 years as per the phase I study results. This thread is about Shiseido and RCH-01. Not Tsuji.

Tsuji is working on replicating donor hair follicles to create unlimited donor hair for hair transplant. Hair transplants currently work by and large with their only limitation being donor hair which Tsuji is working to solve. So I am not really sure what it is that you are arguing. Tsuji won't work because hair transplants don't work....? Right....

I think his point is the critical factor is the scalp so you transplant the donor to the scalp with androgen receptors the hair follicles underbeneath will suffer.

 

[IdealForehead]

And yet transplanting follices one by one does work....... People get hair transplants and the results last for decades....... I'm not sure why you are trying to complicate things with talk of scalping people and suturing on a new scalp with hair back on.... This seems rather absurd.

Can you please explain to me why do hair transplants currently work and produce long lasting results?

I just did. But I will go through it again with two examples to contrast. Basically, it's a matter of time and aggressiveness of your hairloss.

- If you are 50 years old and get a transplant, the occipital hair has been protected from galeal stress your entire life. It is pristine. At 50, it will have taken 35 years of mechanical/androgenic damage since puberty to erode your hairline to the point of needing the transplant in the first place. This means it might take another 35 years for any newly transplanted hair from the occipital scalp to suffer the same fate. In fact, it might take longer, as your androgen levels drop with age. By that point you will be in your 80s and it will be irrelevant. So a hair transplant at 50 in this condition may well last you your entire life without even taking finasteride.

- However, if you are 25 years old and have already reached transplantable levels of hair loss (NW3+), this suggests you are extremely susceptible to androgenic damage triggered by galeal stress, as it has only taken ~10 years since your puberty to accumulate this level of damage. Many hair transplant surgeons are actually quite nervous to offer ANY transplant in this condition, and almost all will require you to agree to taking finasteride for life to protect their work as well as your remaining hair. This pattern of hairloss would suggest that with nothing to protect your hair (like finasteride), in another 10 years the androgenic damage will again have accumulated to critical levels and even this transplanted hair will begin to fail (by age 35).

This is consistent with what we see on this forum regularly and what most guys who have had transplants will tell you. Guys who have aggressive hairloss and don't take finasteride after transplantation tend to do very poorly overall. Guys who have aggressive hairloss and then stop their finasteride a few years after transplantation also tend to do poorly. This is why ethical transplant surgeons don't like operating on these cases.

 

[Feelsbadman.jpg]

From https://www.sciencedirect.com/science/article/pii/S0022202X15529382


Cells from follicles derived from androgen-sensitive sites, including human beard (Randall et al, 1992) and balding scalp (Hibberts et al, 1998) and red deer mane (Thornton et al, 2001) follicles, contained low capacity, high affinity androgen receptors at higher concentrations than those from nonbalding follicles. There were no differences in the binding affinity of the receptors from the different sites for a range of androgenic and other steroids. Studies of the ability of dermal papilla cells to metabolize testosterone intracellularly to its biologically more active form, 5α-dihydrotestosterone, have shown that this capacity reflects the limited beard growth, but strong axillary and female pattern pubic hair growth, in patients suffering from 5α-reductase deficiency (Wilson et al, 1993; reviewed inRandall, 2000). Beard dermal papilla cells readily form 5α-dihydrotestosterone (Itami et al, 1991;Thornton et al, 1993) unlike nonbalding scalp or pubic and axillary follicles (Hamada et al, 1996). This marked parallel with hair growth in patients lacking 5α-reductase type 2 provides strong support for the hypothesis that androgens in the follicle act via the dermal papilla; it also supports the usefulness of dermal papilla cells to study androgen action since their gene expression in vitro appears to reflect that in vivo.

Factors produced by dermal papilla cells from various sites have been examined, often using conditioned media, i.e., media in which dermal papilla cells have been grown and into which they have released their products. Conditioned media has stimulated the growth of other dermal papilla cells (Thornton et al, 1998), hair follicle outer root sheath cells (Limat et al, 1993) and epidermal keratinocytes (Hibberts and Randall, 1996). Importantly, the addition of testosterone to the dermal papilla cells increased the mitogenic capacity of beard cell media (Itami et al, 1995;Thornton et al, 1998), but decreased that from balding scalp from both men (Hibberts and Randall, 1996) and the macaque (Obana et al, 1997) This again reflects in vitro what would be predicted from observations of hair growth in vivo. The current emphasis of research (reviewed inRandall et al, 2001) is in identifying factors produced differently by dermal papilla cells in response to testosterone, such as insulin-like growth factor (IGF-1) (Itami et al, 1995) and stem cell factor (SCF), a regulator of melanocytes (Hibberts et al, 1996).

In conclusion, cultured dermal papilla cells are not an easy model to use and have significant disadvantages in the need for full depth skin samples, their slow growth rate and generally short-lived nature (Messenger, 1984;Randall, 1996). However, they do offer very important advantages. These include: the possibility of investigating the paradoxical differences in androgen responses between follicles from various sites; their ability to induce hair growth when reimplanted in vivo; the retention of a gene expression in vitro which appears to reflect in vivo aspects of hair growth. Overall, this makes them a useful tool to address certain specific questions. However, it is essential that the appropriate types of cells are studied to address particular questions, e.g., only those derived from follicles which are sensitive to androgens in vivo to investigate androgen action.





Even without mechanical tension from the galea, Dermal papilla cells atrophy in the prescence of androgens. Not just in humans, but also stump tailed macaques. So basically if you take a dermal papilla cell and isolate it away from the body and expose it to androgens, same thing happens as on the body. Also, I believe there are studies showing that if you take DP cells from the non balding zones and expose them to high enough concentration of androgens, they too will start to atrophy.

 

[IdealForehead]

Even without mechanical tension from the galea, Dermal papilla cells atrophy in the prescence of androgens. Not just in humans, but also stump tailed macaques. So basically if you take a dermal papilla cell and isolate it away from the body and expose it to androgens, same thing happens as on the body. Also, I believe there are studies showing that if you take DP cells from the non balding zones and expose them to high enough concentration of androgens, they too will start to atrophy.

Absolutely that's what should be expected to happen and that makes sense in the context of this approach to understanding hair loss.

The principle of galeal stress is that galeal stress is the primary instigator which sets off the androgenic chemical cascade. This cascade leads to excess DHT accumulating in the areas which develop hair loss, as well as increased androgen sensitivity of the hair follicles as they upregulate transcription for androgen sensitivity genes.

The androgens are still what kill the hair follicles on a chemical level. But the unanswered question up to now has been: Why does male pattern baldness afflict us in the Norwood pattern? And why is it only skin over the galea that typically goes bald?

And I think we have adequate answers at this point to explain why. Those answers have massive ramifications for understanding how future treatments may or may not be able to "cure" us.

If you're interested in learning more about how scalp tension is highest in the areas that bald first, this is the article from 2015 which best explains the mechanics:

http://www.ijtrichology.com/article...ssue=3;spage=95;epage=99;aulast=Tellez-Segura

They used Finite Element Analysis, which is a common technique used in mechanical engineering to predict mechanical stresses, eg. for predicting how engine parts or buildings will hold up under stress, etc. Using this technique, they 3D-modeled the scalp and the direction of tension which should be exerted on it by the muscles. And when they studied the tension distribution that resulted, surprise suprise - it matched the Norwood pattern quite well.

Here is a graphical representation of their final finding. The picture on the left is their result. The picture on the right is the standard Norwood pattern. As you can see, they match very well.

Areas of highest stress (corners and crown) bald first, and the rest goes later.

 

[InBeforeTheCure]

Only they don't subscribe to your belief that it is androgen receptors in the skin that make the difference between hair on top and hair in the back. They suggest that whether or not the skin and hair sits over the the galea or not is the fundamental difference.

It isn't. Every transplantation study proves this wrong. Move terminal occipital HFs to your arm and they stay terminal. Move miniaturizing HFs to your arm and they continue to miniaturize at the same rate as the neighbors they left behind.Nordstrom's study:

The author transplanted composite skin grafts from balding, non-balding, and bald areas of the scalp, to the skin of the arm. The galea aponeurotica was trimmed away from the grafts. The patient was a 29-yr-old male with progresive male pattern baldness (male pattern baldness). The transplants from the balding area became bald at the same rate as the balding donor site in the receding frontal, hairline, whereas the transplants taken from the non-balding area in the occiput continued to grow the same amount and quality of terminal hairs. Bald grafts taken in front of the receding hairline remained bald. This shows that the cause of male pattern baldness lies in the follicle itself or in its very close surrounding and does not depend on the galea aponeurotica, the increased tension of the scalp or of its muscles, the diminished vascular supply to the scalp or any other regional factor localized to the head area. It also shows that the 'balding clock' keeps time even when the follicle is transplanted to another region of the body.

They discuss how hair transplants are successful only because they take healthy skin with them, and because they haven't been exposed to decades of inflammation already, so might take decades to "fail" even if they inevitably will.

Orentreich 1970:

After 15 years of observation, the hair in the donor grafts in the recipient sites is still growing with the characteristics of the hair in the donor sites. In thousands of transplant procedures performed by us and by hundreds of other physicians, there has been no instance of donor hair-bearing grafts failing to continue the hair growth initially accomplished, if the donor site is still in an area of the scalp that is growing hair. Great care must be taken to select the donor area with an eye toward the future pattern of alopecia formation.

And the direct test of this "explanation" is this: Take occipital HFs and transplant them to the frontal hairline and see if they miniaturize after a comparable time of androgen exposure as the native HFs do. Uno and Montagna did this experiment in stump-tailed macaques, who start receding almost as soon as they hit adolescence and the androgens start flowing. How long do occipital HFs survive when transplanted to the frontal scalp of stump-tailed macaques? Eight years at the very least.

Plugs of occipital hairy scalp and pieces of digital pads were transplanted to the frontal scalp of stump-tailed macaques (Macaca arctoides). Both types of grafts grew well and retained their original appearance for several years. We traced the regrowth and reinnervation of hair follicles and Meissner corpuscles in sequential biopsy specimens of these grafts. Two weeks after transplantation, hair follicles in the grafts appeared to have lost all integrity but began to regrow after 4 weeks. The nerve and organs of hair follicles began to reappear at 8 weeks. Thereafter, grafts with large terminal hairs remained viable in the host bald frontal scalp for as long as 8 yr. In the digital skin grafts, the cytoskeleton of the Meissner corpuscles could be distinguished after 4 weeks; after 8 weeks nerves from the host tissue could be traced to the end organs. Perivascular nerve plexuses and nerves to the piloarrector muscles were clearly seen in both types of graft after 8 weeks.

Seven years after transplantation, the graft skin still had large terminal hair follicles with no sign of regressive changes. All the follicles in the graft skin had intact nerve end organs and the piloarrector muscles were well innervated.

Source: Uno & Montagna, 1982

Or how about this one: Take pre-pubertal female macaques (the females macaques also get A.G.A) and remove their ovaries so they can't produce testosterone. Transplant frontal HFs to occipital scalp, and occipital HFs to frontal scalp. If what Johnny English is saying is true, after injecting these monkeys with testosterone, the occipital HFs transplanted to frontal scalp will miniaturize, while the frontal HFs transplanted to occipital scalp will remain terminal. If the "standard model" is true, we should expect the opposite. And - surprise, surprise - the opposite is what really happens.

One and one-half months later, the hair on the frontal punches became coarse and long like that in the occipital scalp. At that time, the dose of testosterone was increased to 10 mg/week given in two injections; this seemed to accelerate the thinning process of the hairs on the frontal area. One month later, when the total amount of testosterone was to 160 mg, the hairs of the left frontal area and of the medial half of flap A became vellus type, though they were slightly longer than those of adult male animals. By this time, the hair on the occipital punches, which originated from the frontal area, had become thinner and shorter than the surrounding occipital hair. On the sixth month after the beginning of hormone therapy, the dosage of testosterone was increased to two weekly injections of 12.5 mg and on the ninth month to two weekly injections of 15.0 mg. The animal was maintained at this level until the end of the observations, one year after the beginning of therapy. During this time the hair on the right frontal area and on the inner half of flap A became thinner, and then shorter. The hair on the frontal punches became coarse and long, whereas the hair on the occipital punches became thinner and shorter, even more rapidly than the hair remaining in the original frontal area.

Source: Takashima & Montagna, 1971

As for "decades of inflammation" - also dead wrong. Jaworsky's study found lymphocytic infiltrates around HFs in bald areas and adjacent transitional zones, but not DIRECTLY behind this where hair loss hadn't started yet. Inflammation is seen only around actively miniaturizing (and miniaturized) follicles.

Which is in all honesty the only thing that we've seen that can explain the difference between scalp on top and scalp in the back and geographic pattern of hair loss we see in men:

Only...It's wrong. And how do you rule out other potential explanations, for example positional epigenetic differences - the same principle known to govern other hair growth traits (like glabrous vs. hair-bearing skin)? Cultured hair follicles from sites near each other are already known to respond differently to androgens. Why can't that explain the difference?

Anti-androgens work because they block the inflammation cascade that occurs from the galea's negative effects. But the galea is almost certainly the underlying cause.

Reality disagrees.

 

[IdealForehead]

It isn't. Every transplantation study proves this wrong. Move terminal occipital HFs to your arm and they stay terminal. Move miniaturizing HFs to your arm and they continue to miniaturize at the same rate as the neighbors they left behind.Nordstrom's study:





Orentreich 1970:



And the direct test of this "explanation" is this: Take occipital HFs and transplant them to the frontal hairline and see if they miniaturize after a comparable time of androgen exposure as the native HFs do. Uno and Montagna did this experiment in stump-tailed macaques, who start receding almost as soon as they hit adolescence and the androgens start flowing. How long do occipital HFs survive when transplanted to the frontal scalp of stump-tailed macaques? Eight years at the very least.





Source: Uno & Montagna, 1982

Or how about this one: Take pre-pubertal female macaques (the females macaques also get A.G.A) and remove their ovaries so they can't produce testosterone. Transplant frontal HFs to occipital scalp, and occipital HFs to frontal scalp. If what Johnny English is saying is true, after injecting these monkeys with testosterone, the occipital HFs transplanted to frontal scalp will miniaturize, while the frontal HFs transplanted to occipital scalp will remain terminal. If the "standard model" is true, we should expect the opposite. And - surprise, surprise - the opposite is what really happens.



Source: Takashima & Montagna, 1971

As for "decades of inflammation" - also dead wrong. Jaworsky's study found lymphocytic infiltrates around HFs in bald areas and adjacent transitional zones, but not DIRECTLY behind this where hair loss hadn't started yet. Inflammation is seen only around actively miniaturizing (and miniaturized) follicles.



Only...It's wrong. And how do you rule out other potential explanations, for example positional epigenetic differences - the same principle known to govern other hair growth traits (like glabrous vs. hair-bearing skin)? Cultured hair follicles from sites near each other are already known to respond differently to androgens. Why can't that explain the difference?



Reality disagrees.

I know you don't personally believe in this explanation for hair loss. However, I don't think anything you've said refutes the principle of the galea being the underlying cause of hair loss or the recent studies that have been published to support this explanation.

Nordstom's findings were reflected upon here, in the study where they analyzed expected galeal stress patterns and found them to match the Norwood hair loss pattern exactly:

The involvement of mechanical stress in Androgenetic Alopecia implies that hair follicles do not have genetically preprogramed androgen sensitivity. It is imperative at this point to mention the ingenious experiment by Nordstrom, who transplanted hair follicles from both balding and occipital scalp to the forearm. The result was the loss of hair from the balding scalp whereas the occipital hair continued growing.[32] This study is considered a proof of genetic follicle preprograming, but according to the approach of the present paper, it would be necessary to know the strain supported by the forearm skin and to realize that the hair follicles close to receding hairline have already started a countdown toward the miniaturization, but not the occipital follicles. In hair transplantation, the grafted follicles start a new "balding clock," but hair growth would be guaranteed for many years even without preventive pharmacotherapy.​

How do you explain that balding matches the expected tension distribution of the galea? How do you explain that Botox therapy to the scalp can increase hair growth significantly?

Here is the conventional explanation for the effectiveness of Botox for hair growth, which also recognizes tension as a primary mediator of androgenic hair loss:

The proposed mechanism for hair growth in androgenic alopecia after botulinum toxin A treatment is that paralysis of the scalp muscles enhances blood flow to the scalp by reducing the tension on the scalp skin. Because the conversion to dihydrotestosterone (DHT) is enhanced in a low-oxygen environment, oxygenated blood reduces this conversion and increases conversion to estradiol. This might be the same mechanism by which minoxidil affects androgenic alopecia. The 18% increase in hair count is similar to that achieved with finasteride. How injecting BTX A into scalp muscles could be protected as intellectual property is difficult to see.

https://www.jwatch.org/jd201111100000001/2011/11/10/growing-hair-with-botox​

This explanation as a whole suggests that the galea likely causes epigenetic changes to the hair follicles, by inducing specific genes to upregulate (androgen production and androgen sensitivity) in response to tension during development and lifespan.

Transplantation is a difficult thing to speculate on in the context of this model, because we don't know how long it would take to reverse the positive genetic switches that the occipital scalp turns on and replace them with the negative switches the galea would turn on. We also don't know how much of the mechanical stress from the galea will transmit to transplanted hair compared to native hair over time to change these switches.

Dermis associated with native hair in balding prone scalp is considered to be "fused" to the galea. What about dermis associated with transplanted hair? Transplantation is an artificial surgical process. Would the same "fusion" occur to equally transmit mechanical stress?

If transplanted hair truly does survive very well (decades) even in young balding men in the absence of anti-androgens like finasteride (and I am highly skeptical this is the case as I have seen disastrous examples of guys who have had transplants and not taken their meds after), it would suggest primarily that either the epigenetics induced by developing in the occipital scalp are resistant to change or that the mechanical process of transplantation keeps the transplanted hair "unloaded" from the galea.

So I don't think anything you're saying undermines the basic principle of this model. This model still best explains the distribution of hair loss that is seen with male pattern baldness. It just suggests we don't really know how transplanted hair reacts to relocation in the context of this model.

 

[Hate da Bt]

I know you don't personally believe in this explanation for hair loss. However, I don't think anything you've said refutes the principle of the galea being the underlying cause of hair loss or the recent studies that have been published to support this explanation.

Nordstom's findings were reflected upon here, in the study where they analyzed expected galeal stress patterns and found them to match the Norwood hair loss pattern exactly:

The involvement of mechanical stress in Androgenetic Alopecia implies that hair follicles do not have genetically preprogramed androgen sensitivity. It is imperative at this point to mention the ingenious experiment by Nordstrom, who transplanted hair follicles from both balding and occipital scalp to the forearm. The result was the loss of hair from the balding scalp whereas the occipital hair continued growing.[32] This study is considered a proof of genetic follicle preprograming, but according to the approach of the present paper, it would be necessary to know the strain supported by the forearm skin and to realize that the hair follicles close to receding hairline have already started a countdown toward the miniaturization, but not the occipital follicles. In hair transplantation, the grafted follicles start a new "balding clock," but hair growth would be guaranteed for many years even without preventive pharmacotherapy.​

How do you explain that balding matches the expected tension distribution of the galea? How do you explain that Botox therapy to the scalp can increase hair growth significantly?

Here is the conventional explanation for the effectiveness of Botox for hair growth, which also recognizes tension as a primary mediator of androgenic hair loss:

The proposed mechanism for hair growth in androgenic alopecia after botulinum toxin A treatment is that paralysis of the scalp muscles enhances blood flow to the scalp by reducing the tension on the scalp skin. Because the conversion to dihydrotestosterone (DHT) is enhanced in a low-oxygen environment, oxygenated blood reduces this conversion and increases conversion to estradiol. This might be the same mechanism by which minoxidil affects androgenic alopecia. The 18% increase in hair count is similar to that achieved with finasteride. How injecting BTX A into scalp muscles could be protected as intellectual property is difficult to see.

https://www.jwatch.org/jd201111100000001/2011/11/10/growing-hair-with-botox​

This explanation as a whole suggests that the galea likely causes epigenetic changes to the hair follicles, by inducing specific genes to upregulate (androgen production and androgen sensitivity) in response to tension during development and lifespan.

Transplantation is a difficult thing to speculate on in the context of this model, because we don't know how long it would take to reverse the positive genetic switches that the occipital scalp turns on and replace them with the negative switches the galea would turn on. We also don't know how much of the mechanical stress from the galea will transmit to transplanted hair compared to native hair over time to change these switches.

Dermis associated with native hair in balding prone scalp is considered to be "fused" to the galea. What about dermis associated with transplanted hair? Transplantation is an artificial surgical process. Would the same "fusion" occur to equally transmit mechanical stress?

If transplanted hair truly does survive very well (decades) even in young balding men in the absence of anti-androgens like finasteride (and I am highly skeptical this is the case as I have seen disastrous examples of guys who have had transplants and not taken their meds after), it would suggest primarily that either the epigenetics induced by developing in the occipital scalp are resistant to change or that the mechanical process of transplantation keeps the transplanted hair "unloaded" from the galea.

So I don't think anything you're saying undermines the basic principle of this model. This model still best explains the distribution of hair loss that is seen with male pattern baldness. It just suggests we don't really know how transplanted hair reacts to relocation in the context of this model.

This ain't the proper thread to talk about the galea tension theory, pal.

 

[IdealForehead]

This ain't the proper thread to talk about the galea tension theory, pal.

That's fair. We've gotten way off topic. But as with any thread the chances of staying on topic tend to drop precipitously after about page 5.

I'll make a new thread since I think it's worth discussing more.