Neogenesis of the Human Hair Follicle by AM Kligman

Stem cell; cell based hair therapy
1

This is the paper published by Kligman in 1959. Unfortunately I can only see the first page, does anyone have access to this? Perhaps at a university. This is interesting because it focuses on human subjects rather than the mice studies we’ve seen.

http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1960.tb40924.x/abstract

2

Isn’t it astounding that 2012 - 1959 = 53 years ! have gone by and STILL there’s not been jack sh&t for progress in curing baldness. I mean literally fu&king zero as far as progress can be measured.

The level of incompetence in this field is beyond belief.

You can imagine the horror of a bald guy living in the mid 50s if he was told baldness would never be cured in his lifetime. He was probably thinking given the advances of WWII, the cure can’t be more than 5 years away.

Anyway, I don’t think it costs anything to register to get the entire PDF. I haven’t done it so I don’t know for sure. If you do register and get the PDF, please post it somewhere so the rest of us can read it.

3

LOL, I was just skimming through a Follica patent and found a reference to another, earlier dermabrasion study by Kligman. Thanks for the find, KO. IMO, this is proof of concept that Follica’s approach - at least theoretically - is applicable to humans as well as mice as far as hair follicle neogenesis goes. Even if the neogenic hair follicles just come out vellus, we have seen previously from the DIY:ers’ experiments that the conversion from vellus to terminal indeed is a real possibility, suggesting that terminal hairs can be created anew.

Anyhow, here’s Kligman’s study: https://anonfiles.com/cdn/1321911163884.pdf

Note the last footnote: “Very recently Paul Gross and I have observed regeneration of moderately-sized follicles in scalp scars left after excision of the top 1 to 2 mm. of skin.”

@Freddie: There was never any research initiatives to get this working. As you probably already know, the common belief up until very recently was that we are born with a fixed number of hair follicles. Kligman was a dermatologist, who did quite substantial research in the treatment of acne, as far as I can tell. Naturally, he also performed acne scar treatments, of which dermabrasion is very common. This research just stems from observations made from his clinical practice.

4

Excellent find. Although should note, that Kligman used dermabrasion on the face, rather than scalp I believe, so he generated vellus follicles.

I believe in the follica patent they note that a few in the control group without lithium treatment grew follicles:

"[00660] Thirteen of the 15 enrolled subjects had skin biopsies in each of their two dermabraded sites. Two of these 13 subjects ( 15%) had neogenic-like hair follicles present in both their left and right sites, for a total of four positive biopsies out of 26 adequate biopsies ( 15%).

[00661] Ten subjects had biopsies of the control sites. No neogenic-like hair follicles were present where there had been no dermabrasion."

This lithium patent interestingly enough is also something they’re aiming at to reduce* hair growth as well as increase it. Anyways, this looks promising.

5

Cool, I hadn’t read through those patent claims before. :ok:

2 of 13 might not be amazing, but it seems Follica is far less aggressive in their dermabrasion than Kligman:

“[00638] Dermabrasion using alumina particles is performed on Day 0. Dermabrasion is performed to a depth of approximately 100 uM, which includes removal of the entire epidermis and disruption of the papillary dermis (detectable by a shiny, whitish appearance) inducing the formation of small pinpoints of blood in the treated area.”

100 um should translate to 0.1 mm if my math isn’t completely messed up, while Kligman dermabraded away 2 mm, down to mid-dermis (is that even possible without scarring?) Anyway, I’d expect Follica to experience significantly greater success when they incorporate lithium + fractional laser as per their most recent patent.

Also, if memory serves me right, I think I read in a study published in yet another Follica patent, that they didn’t see any neogenic follicles after dermabrasion in mice (only post FTE). I don’t know if that should be seen as positive or negative, since it, in a sense, would imply that humans do respond to this type of treatment perhaps even as well as mice do in light of the above.

Btw, did you guys notice the faculty credential (word?) in Kligman’s paper? “Department of Dermatology, University of Pennsylvania, Philadelphia, Pa.” - …where else? :smiley:

6

Clearly a switched on guy, I recognised that name as the inventor of Retin-A.

7

Absolutely. Mayumi Ito saw neogenic hair follicles in the mice when they were doing the experiments, and she looked through the literature and found 3 papers from the 50s/60s, and this one was the one that mentioned the possibility of neogenesis. A few years later Kligman’s claims were brushed off as cells migrating from the outside to the wound (wtf), and this line of inquiry was abandoned. A few years before Kligman’s study,also at UPenn, Charles Breedis also found neogenic follicles in rabbits.

8

» Isn’t it astounding that 2012 - 1959 = 53 years ! have gone by and STILL
» there’s not been jack sh&t for progress in curing baldness. I mean
» literally fu&king zero as far as progress can be measured.
»
» The level of incompetence in this field is beyond belief.
»
» You can imagine the horror of a bald guy living in the mid 50s if he was
» told baldness would never be cured in his lifetime. He was probably
» thinking given the advances of WWII, the cure can’t be more than 5 years
» away.
»
» Anyway, I don’t think it costs anything to register to get the entire PDF.
» I haven’t done it so I don’t know for sure. If you do register and get the
» PDF, please post it somewhere so the rest of us can read it.

get used to being ugly, AND bald

9

» Absolutely. Mayumi Ito saw neogenic hair follicles in the mice when they
» were doing the experiments, and she looked through the literature and found
» 3 papers from the 50s/60s, and this one was the one that mentioned the
» possibility of neogenesis. A few years later Kligman’s claims were brushed
» off as cells migrating from the outside to the wound (wtf), and this line
» of inquiry was abandoned. A few years before Kligman’s study,also at UPenn,
» Charles Breedis also found neogenic follicles in rabbits.

Thanks for the info :cool: This line of research is by far the most interesting atm in my opinion. It might be that it will have to be combined with some other methodology to give any substantial results, but the prospect of an innate ability of actual tissue regeneration is enough to get me more than excited :slight_smile: cheers!

10

» » Absolutely. Mayumi Ito saw neogenic hair follicles in the mice when they
» » were doing the experiments, and she looked through the literature and
» found
» » 3 papers from the 50s/60s, and this one was the one that mentioned the
» » possibility of neogenesis. A few years later Kligman’s claims were
» brushed
» » off as cells migrating from the outside to the wound (wtf), and this
» line
» » of inquiry was abandoned. A few years before Kligman’s study,also at
» UPenn,
» » Charles Breedis also found neogenic follicles in rabbits.
»
» Thanks for the info :cool: This line of research is by far the most
» interesting atm in my opinion. It might be that it will have to be combined
» with some other methodology to give any substantial results, but the
» prospect of an innate ability of actual tissue regeneration is enough to
» get me more than excited :slight_smile: cheers!

Agree, at least this was done in humans and not mice.

11

Yeah it appears that Follica is pretty confident. Only time will tell though.

It really would be shocking if the treatment was something as simple as dermabrasion and topical lithium for 10 weeks. But I agree with you guys, I think that to make this stuff most useful, it should be combined with every other treatment we have, whether it be fin, min, or HT’s.

Interestingly enough, in the Follica patent, they also describe that the same treatment can be used to treat excessive hair growth as well as hair loss. I do not totally understand that line of logic.

12

Here is another interesting article.

Guess what lithium does to beta-catenin?

13

Hey kekeke, how does this anonfiles site work? I’m looking to find more articles from nature/other journals without paying. :slight_smile: For example, this one:

http://www.nature.com/nbt/journal/v29/n6/full/nbt.1887.html?WT.ec_id=NBT-201106

14

Here’s an interesting study on similar lines to Ito et al. However, they generated only rudimentary hair follicles and cysts.

15

Here is an article that is sort of a bio of Cotsarelis and talks about “the experiment”.

http://www.uphs.upenn.edu/news/publications/PENNMedicine/files/PENNMedicine_2009_01_winter10_Hair_Cotsarelis.pdf

The key discovery here is, apart from the fact that follicles fan form de novo in skin, it’s important to note that the cells responsible for neogenesis were not stem cells located in the hair follicle bulge, but rather that they were epidermal cells. Since melanocytes are in the hair follicle bulge in mice rather than epidermis, that explains why they produced unpigmented, white hairs.

Dammit, I just hope they get it to work lol.

16

» Hey kekeke, how does this anonfiles site work? I’m looking to find more
» articles from nature/other journals without paying. :slight_smile: For example, this
» one:
»
» Raising hairs | Nature Biotechnology

Hey KO, sorry I missed this, haven’t been back here for a while.

I have access to most journal databases through my university. Send me a list of the articles that you’re interested in, and I’ll see what I can do.

Can’t seem to find any PM function on this board though. Are you on any other, by any chance? IP paranoia perhaps, but I’d prefer not to share too many publicly (PMs are fine.)

17

» Here’s an interesting study on similar lines to Ito et al. However, they
» generated only rudimentary hair follicles and cysts.
»
» Wnt signaling induces epithelial differentiation during cutaneous wound healing | BMC Molecular and Cell Biology | Full Text

yea, i’ve seen this one before. Not too encouraging in a way, seeing as the principal difference only seems to lie in that they made smaller wounds (that are still very big, though, so there will be major scarring.)

What would be interesting to know is, say you manage to induce the formation of a stage 4 follicle, will you then be able to “build” on that result so as to develop that follicle into a more mature stage by repeating the protocol? In one of the Follica patents, I remember seeing that they had a diagram of which stages the neogenic hair follicles had made it to from an FTE experiment, and very few were stage 8 if I remember correctly.

18

Yeah, it might be a problem turning rudimentary follicles into mature follicles. I think the problem here is that lithium is being used as the active ingredient. Perhaps by adding growth factors like Histogen?

Lithium promotes differentiation into cells by mimicking the Wnt pathway. But on the other hand it actually stops cell mitosis, and puts them into a metaphase arrest. This may be one of the reasons that the hair follicles don’t develop into terminal ones. I believe this may be the case so I think what Follica is doing is using intermittent treatments, so basically regular pulse injections of lithium, whereas Fathke used continuous lithium treatment.

19

I definitely understand, I’m on “h.a.i.r.l.o.s.s.h.e.l.p dot com” as the same user id “KO”, there is private messaging on that forum. If you want, I’ll create a new email address to post on this site.

Here are the articles I’m interested in, I think the second one may be of interest to this forum.

http://onlinelibrary.wiley.com/doi/10.1111/j.1524-4725.2011.01934.x/full
http://www.nature.com/nbt/journal/v29/n6/full/nbt.1887.html?WT.ec_id=NBT-201106

20

» Yeah, it might be a problem turning rudimentary follicles into mature
» follicles. I think the problem here is that lithium is being used as the
» active ingredient. Perhaps by adding growth factors like Histogen?
»
» Lithium promotes differentiation into cells by mimicking the Wnt pathway.
» But on the other hand it actually stops cell mitosis, and puts them into a
» metaphase arrest. This may be one of the reasons that the hair follicles
» don’t develop into terminal ones. I believe this may be the case so I think
» what Follica is doing is using intermittent treatments, so basically
» regular pulse injections of lithium, whereas Fathke used continuous lithium
» treatment.

That’s an interesting theory, didn’t know about that. Quick googling turned up this:

“Treatment with LiCl earlier in prophase also results in metaphase arrest. Metaphase arrest can be reversed by the addition of 10 microM myo-inositol or 100 microM CaCl2 to the extracellular medium. The timing of reversal by myo-inositol takes 10 to 14 min while CaCl2 promotes anaphase onset in 2 to 5 min. The difference in kinetics for reversal between these two treatments suggests that myo-inositol addition overrides a biochemical pathway while Ca2+ addition supplants a phosphoinositide-mediated rise in the cation that may be necessary for anaphase onset.”

So maybe the addition of calcium ions could, potentially, remediate this effect? Inositol seems to interfere with the lithium, so not sure about that one. GSK-3 phosphorylation by AKT and the HSC, like you said, would also be an interesting addition to the mix.