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There was fibrosis, then they did something to allow hair to grow. They changed it, so how can you assume the fibrosis wasn't changed
Researchers Regrow Hair On Wounded Skin
- Thread starter c_super2
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What they're saying is they can take a chunk of scar tissue and use SSH to cause Hair Follicle Neogenesis in the tissue despite the fibrosis.
Our study suggests that scarring/fibrosis in skin wounds may not affect HF morphogenesis if the appropriate regenerative ques are applied. Although long-term activation of Wnt signaling, a hallmark of fibrotic repair, was observed in small wounds, the physiological level of Wnt signaling in scarring wounds did not negatively impact HFN in the presence of Shh activation.
What this seems to be saying is that SSH is so powerful that it looks like nothing can stop it. They state it's necessary and sufficient for HFN in wound healing. If that's true, then this is the only pathway that needs to be activated.... So assuming this proves to be safe, it would be the one stop cure for all alopecias.
It's not saying perifollicular fibrosis isn't a contributing factor in the pathology of Androgenetic Alopecia.
I really had no idea SHH was this promising though, I mean Jesus.
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Here's a little summary of the study that answers some of these questions @Arrade @BetaBoy @arnoldd @bboy:
- In mice, small skin wounds result in formation of scar tissue (fibrosis), composed largely of Extracellular Matrix (ECM) components like collagen and fibronectin and devoid of hair follicles (HFs). Only large wounds develop HFs, and only in the center.
- In humans, both large and small wounds almost always undergo fibrotic scarring.
- In mice, expression of Sonic Hedgehog (Shh) in overlying epidermis induces HF formation in small wounds and outside the centers of large wounds. This is of course different from what normally happens.
- Dermal Shh upregulates many dermal papilla cell (DPC)-specific genes in myofibroblasts (a type of cell found in scars) - myofibroblasts are converted into DPCs. These genes include hair-inducing signaling molecules like FGF10, R-spondin 3, BMP4, BMP7, etc.
- Both dermal Wnt and Shh are required for DP formation and hair induction. Shh activation in Wnt-active fibroblasts within wounds drives DP formation. Wnt alone drives fibrosis. Both Wnt and Shh are necessary to make DPCs in adult skin.
- There is no change in ECM composition (i.e. no change in collagen fiber diameter/fibrosis) due to Shh overexpression. The hair follicles grow within the scars.
- From the authors: "Our results suggest that the suppression of skin appendage regeneration in wound healing is due to the absence of dermal regeneration signals rather than intrinsic lack of regenerative competence in scarring cells."
- Also from the authors: "Our study suggests that scarring/fibrosis in skin wounds may not affect HF morphogenesis if the appropriate regenerative cues are applied. Although long-term activation of Wnt signaling, a hallmark of fibrotic repair, was observed in small wounds, the physiological level of Wnt signaling in scarring wounds did not negatively impact HFN [hair follicle neogenesis] in the presence of Shh activation."
- In mice, small skin wounds result in formation of scar tissue (fibrosis), composed largely of Extracellular Matrix (ECM) components like collagen and fibronectin and devoid of hair follicles (HFs). Only large wounds develop HFs, and only in the center.
- In humans, both large and small wounds almost always undergo fibrotic scarring.
- In mice, expression of Sonic Hedgehog (Shh) in overlying epidermis induces HF formation in small wounds and outside the centers of large wounds. This is of course different from what normally happens.
- Dermal Shh upregulates many dermal papilla cell (DPC)-specific genes in myofibroblasts (a type of cell found in scars) - myofibroblasts are converted into DPCs. These genes include hair-inducing signaling molecules like FGF10, R-spondin 3, BMP4, BMP7, etc.
- Both dermal Wnt and Shh are required for DP formation and hair induction. Shh activation in Wnt-active fibroblasts within wounds drives DP formation. Wnt alone drives fibrosis. Both Wnt and Shh are necessary to make DPCs in adult skin.
- There is no change in ECM composition (i.e. no change in collagen fiber diameter/fibrosis) due to Shh overexpression. The hair follicles grow within the scars.
- From the authors: "Our results suggest that the suppression of skin appendage regeneration in wound healing is due to the absence of dermal regeneration signals rather than intrinsic lack of regenerative competence in scarring cells."
- Also from the authors: "Our study suggests that scarring/fibrosis in skin wounds may not affect HF morphogenesis if the appropriate regenerative cues are applied. Although long-term activation of Wnt signaling, a hallmark of fibrotic repair, was observed in small wounds, the physiological level of Wnt signaling in scarring wounds did not negatively impact HFN [hair follicle neogenesis] in the presence of Shh activation."
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Hey @InBeforeTheCure , just curious. The hairloss2020 site has this article about SHh:
https://www.hairlosscure2020.com/the-sonic-hedgehog-pathway-an-unrealized-dream/
In summary, this SHH stuff was researched back in 1999. It got dropped around 2005 due to risk of tumour.
Is there anything different between this current research and the one that was done in 1999?
https://www.hairlosscure2020.com/the-sonic-hedgehog-pathway-an-unrealized-dream/
In summary, this SHH stuff was researched back in 1999. It got dropped around 2005 due to risk of tumour.
Is there anything different between this current research and the one that was done in 1999?
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The research done in 1999 was interested in Shh's role in accelerating anagen entry in existing HFs. This latest study is about Shh's role in growing entirely new HFs in wounds.
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So the risk of tumours is low for the current research?
Do you see potential for formation of completely new follicles, terminal hair, arecetor pila muscles etc..?
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If you still have vellus hairs then you don't need new follicles, right?
It's a theory but maybe it is scar tissue in the blood vessels that prevent the hair follicle from growing to a full terminal hair, by blocking blood flow.
Or is scar tissue not present when you still have vellus hairs in the follicle
It's a theory but maybe it is scar tissue in the blood vessels that prevent the hair follicle from growing to a full terminal hair, by blocking blood flow.
Or is scar tissue not present when you still have vellus hairs in the follicle
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Dermaneedling creates restoration environment on your scalp. But can it overcome your balding genes? I don't know.
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You can already replicate this research with wounding+LiCl (for WNT). But that alone doesn't do much. So there have to be other factors that cause baldness.
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To me, it seems that if you have a miniatruized hair then the stem cells are still active.
If you had no stem cell causing growth then why is there still a blonde vellus hair present.
I have already highlighted this before, 7 mths before this latest study of the thread came out:
https://www.hairlosstalk.com/intera...ive-study-gene-expression-differences.113659/
Both studies = loss of hedgehog signalling in Androgenetic Alopecia scalp.
Henceforth, gain of hedghehog signalling = hair regrowth.
Thus, agents that increase hedgehog signalling = key to regrowth.
And the solution is this class of meds already in existance:
https://www.ncbi.nlm.nih.gov/m/pubmed/20439738/
https://www.ncbi.nlm.nih.gov/m/pubmed/22921064/
And they have been proven to cure alopecia totalis
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0560.1977.tb00889.x
https://www.ncbi.nlm.nih.gov/m/pubmed/12833016/
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144550
So GCs that upregulate https://en.m.wikipedia.org/wiki/Smoothened :
https://en.m.wikipedia.org/wiki/Fluticasone_propionate
https://en.m.wikipedia.org/wiki/Clobetasol_propionate
https://en.m.wikipedia.org/wiki/Halcinonide
= Topical creams.
U can get the first 2 from alldaychemist.
You can only get the 3rd from China.
You cant use them 24/7. Cycle them on 5days, off 2days. Not more than 20mins per application.
Im gonna answer this beforehand in anticipation that somebody's gonna ask it:
No, u cant use hydrocortisone or dexamethasone. They do the opposite in that they downregulate the sonic hedgehog gene. Its been mentioned in the 'Gluccocorticoid as Smoothened agonists' studies.
Its the Fluorine-ringed structure in halcinonide, clobetasol and fluticasone that upregulates Smoothened, because Fluorine is a https://en.m.wikipedia.org/wiki/Halogen
https://www.hairlosstalk.com/intera...ive-study-gene-expression-differences.113659/
Both studies = loss of hedgehog signalling in Androgenetic Alopecia scalp.
Henceforth, gain of hedghehog signalling = hair regrowth.
Thus, agents that increase hedgehog signalling = key to regrowth.
And the solution is this class of meds already in existance:
https://www.ncbi.nlm.nih.gov/m/pubmed/20439738/
https://www.ncbi.nlm.nih.gov/m/pubmed/22921064/
And they have been proven to cure alopecia totalis
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0560.1977.tb00889.x
https://www.ncbi.nlm.nih.gov/m/pubmed/12833016/
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144550
So GCs that upregulate https://en.m.wikipedia.org/wiki/Smoothened :
https://en.m.wikipedia.org/wiki/Fluticasone_propionate
https://en.m.wikipedia.org/wiki/Clobetasol_propionate
https://en.m.wikipedia.org/wiki/Halcinonide
= Topical creams.
U can get the first 2 from alldaychemist.
You can only get the 3rd from China.
You cant use them 24/7. Cycle them on 5days, off 2days. Not more than 20mins per application.
Im gonna answer this beforehand in anticipation that somebody's gonna ask it:
No, u cant use hydrocortisone or dexamethasone. They do the opposite in that they downregulate the sonic hedgehog gene. Its been mentioned in the 'Gluccocorticoid as Smoothened agonists' studies.
Its the Fluorine-ringed structure in halcinonide, clobetasol and fluticasone that upregulates Smoothened, because Fluorine is a https://en.m.wikipedia.org/wiki/Halogen
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For the LOLs, read that thread of mine n see how i got laughed at with sarcastic remarks when i said that the endogenous ligand for Sonic Hedgehog was downregulated in Androgenetic Alopecia.
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Anyone tried one of these 3?
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@sktboiboi
Clascoterone (Aka Breezula) is a glucosteroid if I’m not mistaken. However, this stuff is an anti androgen..
Clascoterone (Aka Breezula) is a glucosteroid if I’m not mistaken. However, this stuff is an anti androgen..
I can't find any information on it activating Smoothened. Not all GCs activate the hedgehog pathway. Some even deactivate it.
This research is focusing on SHH, not WNT.
I came back to the forum only after googling for new Androgenetic Alopecia studies n happen to see this recent one by Cotsarelis and the Sonic hedgehog pathway.
I posted my thread in april, talking about the hedgehog pathway, using the Chinese study that discovered this as a reference.
Fast forward 7mths later, Cotsarelis showed the same thing too about the hedgehog pathway bring needed to grow hair in wounds.
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Some gluccorticoids stop all inflammation.
Most stops most inflammation.
You however, cant use them everyday without sides.
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I'm pretty sure SHH is released during wounding too.
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Great info @sktboiboi. Despite Cotsarelis having numerous patents, I have not seen any plan to commercialize this research directly from them. Are you aware of anything in the pipeline?