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Wnt-dependant de novo... A study... hairtech


#1

I am going to type out an article in the bi-monthly magazine from the ISHRS. called “Hair Transplant Forum International”. I will type it out in sections because I am not a fast typist and I fatigue.

The article i believe is a re-print from the journal called “Nature”.

Title: Wnt-dependant de novo hair follicle regeneration in adult mouse after wounding.

"The loss of an adult follicle is considered permanent. The possibility that hair follicles develop de novo following wounding was raised in studies on rabbits and mice and even humans 50 years ago. In this study, the authors show that after wounding, hair follicles form de novo in genetically normal adult mice. Analysis demonstrated that the follicles arise from epithelial cells outside the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem phenotype. Regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype of the skin.

During there studies on wound healing in mice, the authors noticed structures within the center of large healing wounds that resemble early developing hair follicles. The final rather than initial size of the wound seemed to correlate with hair follicle neogenesis

Hair follicles consist of at least 10 different epithelial and mesenchymal cell types geared toward the production of hair. They discovered that hair follicle neogenesis following wounding paralled embryonic follicle development at the molecular level"

The newly formed hair follicles also proliferated normally and generated hair as well as sebbaceous glands. They discovered that although bulge cell progeny migrated to the center of the wounds, they did not persist. Less than3% of the new hair follicles were labelled, suggesting that non-hair follicle bulge cells were the primary source of regenerated follicles. New follicles originated outside from cells outside of the hair follicle stem cell niche. The new follicles arose from cells in the epidermis and/or upper portion of the follicle(infundibulum). Both of these areas are considered to posses stem cells that normally undergo epidermal rather than follicular differentiiation. Their findings are the first to indicate that non-hair follicle stem cells in genetically normal adult mice acquire competence to form follicles in resonse to wounding.

The regenerated follicles produced hairs and cycled up to three times in 90 days after wounding, indicating the presence of funtional stem cells. The new hairs lacked pigment and associated melanocytes suggesting that the melanocyte stem cell niche was not re-established or that it could not be repopulated. In mice, melanocyte precursors localise to the bulge.

Wnt7a has been shown to maintain the hair follicle inducing capacity of cultured dermal papilla cells. The over expression of activated Beta-catenin, an intracellular Wnt effector, in epidermis induces new hair follicles, and exogenous Wnt promotes formation of cysts with hair follicle differentiation; however, to date, there has been no evidence that extracellular Wnt ligands can promote actual hair follicle neogenesis in adult skin.

Thus excess Wnt in combination with wound healing potetiates regeneration of hair follicles, perhaps by altering cell fate and increasing the number of cells competent to produce hair. Wnt signalling in epidermal keratinocytes is required for hair follicle regeneration.

The authors have demonstrated that the wound stimulus is sufficient to trigger regeneration of hair follicles from epithelial cells that do not normally form hair. In their opinion, this raises the possibility of treating acute wounds with modulators of Wnt pathway to decrease scar formation, and treating hairloss by regenerationg follicles through wounding and Wnt pathway activation."

The end

“Nature” (17 May 2007) 447; 326-320


#2

Thanks hairtech for the summary. God, even re-reading the summary gets me excited. Just imagine if 50 years ago scientists hadn’t prematurely dismissed new hair follicle formation following wounding as poppycock… then we’d probably have a cure for baldndess now. Regardless, wounding plus WNT promotion is exciting b/c it’s yet another way of beating this disease… and wounding plus Acell would be a yet another…

» I am going to type out an article in the bi-monthly magazine from the
» ISHRS. called “Hair Transplant Forum International”. I will type it out in
» sections because I am not a fast typist and I fatigue.
»
» The article i believe is a re-print from the journal called “Nature”.
»
» Title: Wnt-dependant de novo hair follicle regeneration in adult mouse
» after wounding.
»
» “The loss of an adult follicle is considered permanent. The possibility
» that hair follicles develop de novo following wounding was raised in
» studies on rabbits and mice and even humans 50 years ago. In this study,
» the authors show that after wounding, hair follicles form de novo in
» genetically normal adult mice. Analysis demonstrated that the follicles
» arise from epithelial cells outside the hair follicle stem cell niche,
» suggesting that epidermal cells in the wound assume a hair follicle stem
» phenotype. Regenerative capabilities of the adult support the notion that
» wounding induces an embryonic phenotype of the skin.
»
» During there studies on wound healing in mice, the authors noticed
» structures within the center of large healing wounds that resemble early
» developing hair follicles. The final rather than initial size of the wound
» seemed to correlate with hair follicle neogenesis
»
» Hair follicles consist of at least 10 different epithelial and mesenchymal
» cell types geared toward the production of hair. They discovered that hair
» follicle neogenesis following wounding paralled embryonic follicle
» development at the molecular level”
»
» The newly formed hair follicles also proliferated normally and generated
» hair as well as sebbaceous glands. They discovered that although bulge
» cell progeny migrated to the center of the wounds, they did not persist.
» Less than3% of the new hair follicles were labelled, suggesting that
» non-hair follicle bulge cells were the primary source of regenerated
» follicles. New follicles originated outside from cells outside of the hair
» follicle stem cell niche. The new follicles arose from cells in the
» epidermis and/or upper portion of the follicle(infundibulum). Both of
» these areas are considered to posses stem cells that normally undergo
» epidermal rather than follicular differentiiation. Their findings are the
» first to indicate that non-hair follicle stem cells in genetically normal
» adult mice acquire competence to form follicles in resonse to wounding.
»
» The regenerated follicles produced hairs and cycled up to three times in
» 90 days after wounding, indicating the presence of funtional stem cells.
» The new hairs lacked pigment and associated melanocytes suggesting that
» the melanocyte stem cell niche was not re-established or that it could not
» be repopulated. In mice, melanocyte precursors localise to the bulge.
»
» Wnt7a has been shown to maintain the hair follicle inducing capacity of
» cultured dermal papilla cells. The over expression of activated
» Beta-catenin, an intracellular Wnt effector, in epidermis induces new hair
» follicles, and exogenous Wnt promotes formation of cysts with hair follicle
» differentiation; however, to date, there has been no evidence that
» extracellular Wnt ligands can promote actual hair follicle neogenesis in
» adult skin.
»
» Thus excess Wnt in combination with wound healing potetiates regeneration
» of hair follicles, perhaps by altering cell fate and increasing the number
» of cells competent to produce hair. Wnt signalling in epidermal
» keratinocytes is required for hair follicle regeneration.
»
» The authors have demonstrated that the wound stimulus is sufficient to
» trigger regeneration of hair follicles from epithelial cells that do not
» normally form hair. In their opinion, this raises the possibility of
» treating acute wounds with modulators of Wnt pathway to decrease scar
» formation, and treating hairloss by regenerationg follicles through
» wounding and Wnt pathway activation."
»
» The end
»
» “Nature” (17 May 2007) 447; 326-320


#3

I am just wondering why Wnt is not part of a rogain mixture. Once day hair tonic.


#4

1 comments and 1 question:

  1. I’ve read that WNT promoters might cause tumors to form… however I don’t know if this has been demonstrated conclusively.
  2. What kind of WNT promoters would you recommend (I’ve only heard that minox has WNT promoting capabilities)? I’d try out my own concoction if I knew how to get ahold of the stuff…

All the best,
BB

» I am just wondering why Wnt is not part of a rogain mixture. Once day hair
» tonic.


#5

» Thus excess Wnt in combination with wound healing potetiates regeneration
» of hair follicles, perhaps by altering cell fate and increasing the number
» of cells competent to produce hair. Wnt signalling in epidermal
» keratinocytes is required for hair follicle regeneration.

I jumped the gun a bit BB.

Wnt under certain conditions promote follicular regeneration. I don’t think we can get Wnt by itself at the local home depot.

I am actually not the savviest in this area also. You guys who regularly post here have got me interested as well as educated me it HM from me reading you guys posts. I understand concepts in HM brought up by you/thegreek/jtelcom/Damon/MPB and a few others.


#6

» The new hairs lacked pigment and associated melanocytes suggesting that
» the melanocyte stem cell niche was not re-established or that it could not
» be repopulated. In mice, melanocyte precursors localise to the bulge.
»

WHat does this statement mean? Was the hair just vellus or did real terminal hairs eventually cycle


#7

I think it means that the hair follicles stem cells were developing fine… however pigment stem cells did not regenerate so the hairs that grew lacked pickment. It does not necessarily mean that the hairs are vellus. just no pigment… white hairs if you will.


#8

It would seem someone could attempt to apply wnt protiens to FUE-extract sites and see what happens.

I thought I read somewhere a while back that minoxidil had a slight upping effect on wnt signalling, but couldn’t refind the info online. I remember a poster at hairlosshell who swore by using a small syringe to inject small amounts of minox and that he had regrowth all over his head, but thats been years ago.

I feel that if wounding the traditional recip area was tried, we’d just get more MPB follicles soon to die, but if the donor area was attempted, one should get follicles with more donor characteristics…whether they be very blonde or white is another matter (might look good if one was already grey though).

ACELL and wnt in the donor area, FUE’ing the traditional hairs up front, would seemingly be a way to “make” more hair for someone.

ONe thing about wnt though…and the beta catenin pathway, when beta catenin was overexpressed in mice, they grew hair like all get out, but they also developed benign tumors in their skin. I’d only want a wnt-protien compound on my dermis for just long enough to get some hair going, and then stop it. We really dont know what would be downstream of it with constant usage over several months in an adult human with an adult human immune system. Its really incredible science though…I appreciate hairtech putting it up.


#9

Hey benji,

I remember reading about minoxidil having some kind of upping effect on the WNT pathway on regrowth.com.

However, check out the interesting thread from regrowth.com:
http://www.regrowth.com/hairloss-forums/viewthread.cfm?f=1&t=16791

Their idea is induce some kind of wounding and then apply lithium cholride, a supposed WNT promoter. (They’ve also suggested DMSO and Retin-A, both of which may enlarge hair follicles.) Their wounding is with needles. I like this approach b/c it follows the scientific literature by Cotsarelis, Fuchs, et al, although the wounding may not be sufficient.

However, one small point: I must disagree with you when you write that new hair follicles would still be susceptible to MPB. IF the wounding is sufficient then the hair follicles are created de novo and will be entirely resistant to MPB. This is shown in anecdotes – a surprising many if you look around – about how people have had scars, wounds etc that have led to new hair growth. (However I suspect new hairs on a DUPA scalp will still be susceptible to miniturization.)

This is interesting/exciting…

All the best,
BB


#10

BB,

Question,…I know where one can get retin-A, but lithium chloride and DBSM? What are those and what are they routinely used for topically, etc?

BTW-----------Id’ be glad to be wrong about new hairs created in the frontal scalp being resistant to MPB, but I was thinking along the lines of whatever wnt-protocol being used in FUE-donor holes in the back, regenerating donor hair, hopefully with donor hair characteristics. SO little has been written about this.

I think I might write Follica and ask them about it, as they have a website now. Its food for thought isn’t it? Im grateful for any step forward on hair…


#11

» It would seem someone could attempt to apply wnt protiens to FUE-extract
» sites and see what happens.

Whoa this is interesting!


#12

Whatever became of AntiCancer INC’s hairloss research and their study of WNT???
www.anticancer.com


#13

What has sparked your sudden interest in HM ?


#14

Here’s the problem, I no longer buy into these mice studies, after reading these forums for so many years I know by now that almost anything can grow hair in mice.


#15

Hey Benji,

  1. Lithium Chloride: boosts WNT signaling; also blocks DHT
  2. DMSO: boosts WNT signaling and increases absorption of lithium chloride

Note that both are TOPICALS only. From my understanding there’s little systemic absorption, however I’d still be concerned inasmuch WNT signaling has been implicated in cancer growth. Nonetheless I’m looking for places to order these compounds and add them to my Revita shampoo. DMSO is available at most health stores, while lithium chloride can be bought online through chemical suppliers.

Best,
BB

» BB,
»
» Question,…I know where one can get retin-A, but lithium
» chloride and DBSM? What are those and what are they routinely used for
» topically, etc?
»
»
»
» BTW-----------Id’ be glad to be wrong about new hairs created in the
» frontal scalp being resistant to MPB, but I was thinking along the lines
» of whatever wnt-protocol being used in FUE-donor holes in the back,
» regenerating donor hair, hopefully with donor hair characteristics. SO
» little has been written about this.
»
»
» I think I might write Follica and ask them about it, as they have a
» website now. Its food for thought isn’t it? Im grateful for any step
» forward on hair…


#16

One other thing… I saw that a guy named “hatchet” over at regrowth.com is using lithium chloride and DMSO combined with needling. HE seems to think he’s inducing stem cell-like conditions that promote regrowth, but I suspect he’s just increasing absorption of lithium and DMSO. I think the wounding needs to be more extensive and relatively deep, as in the case of using a CO2 or Yag-Erbium Laser and/or dermabrasion. The latter is what Follica Inc is looking into doing…

All the best,
BB

» Hey Benji,
»
» 1. Lithium Chloride: boosts WNT signaling; also blocks DHT
» 2. DMSO: boosts WNT signaling and increases absorption of lithium
» chloride
»
» Note that both are TOPICALS only. From my understanding there’s little
» systemic absorption, however I’d still be concerned inasmuch WNT signaling
» has been implicated in cancer growth. Nonetheless I’m looking for places to
» order these compounds and add them to my Revita shampoo. DMSO is available
» at most health stores, while lithium chloride can be bought online through
» chemical suppliers.
»
» Best,
» BB
»
» » BB,
» »
» » Question,…I know where one can get retin-A, but lithium
» » chloride and DBSM? What are those and what are they routinely used for
» » topically, etc?
» »
» »
» »
» » BTW-----------Id’ be glad to be wrong about new hairs created in the
» » frontal scalp being resistant to MPB, but I was thinking along the
» lines
» » of whatever wnt-protocol being used in FUE-donor holes in the back,
» » regenerating donor hair, hopefully with donor hair characteristics. SO
» » little has been written about this.
» »
» »
» » I think I might write Follica and ask them about it, as they have a
» » website now. Its food for thought isn’t it? Im grateful for any step
» » forward on hair…


#17

» I am going to type out an article in the bi-monthly magazine from the
» ISHRS. called “Hair Transplant Forum International”. I will type it out in
» sections because I am not a fast typist and I fatigue.

Thanks for the article. Keep in mind that if you have access to a scanner you can easily convert magazine text into computer text :slight_smile: