Induce hair follicle neogenesis without the help of inductive HF dermal papilla cells

[lacazette]

Sung jan lin is back with good stuff

He had been invited for a presentation in a seminar by the National Institute of Biological Sciences in China

http://webcache.googleusercontent.com/search?q=cache:3y-fcHVlAyUJ:www.nibs.ac.cn/en/lecture/LinSungJan20150817.html+&cd=1&hl=fr&ct=clnk&gl=us

20 August 2015
Speaker:
Sung-Jan Lin, MD, Ph.D.
Topic:
Inducing hair follicle organogenesis with defined protein factors

Abstract:

Neogenesis of the miniorgan of hair follicles depends on the initiation and perpetuation of cross-talk between keratinocytes and dermal cells. We ask whether this epithelial-mesenchymal interaction can be initiated without introducing inductive mesenchymal cells in postnatal life. We found that protein extract from embryonic skin of specific developmental stage was able to induce hair follicle neogenesis both in a full thickness wound and a modified patch assay in mice without the help of inductive hair follicle dermal papilla cells or newborn dermal cells. Hair follicle neogenesis here was mediated mainly through the effect on fibroblasts. When adult fibroblasts, but not keratinocytes, were cultured with the protein extract, they were conferred the ability to induce new hair follicles. Through phosphoproteomic analysis with mass spectrometry, we found that insulin/IGF signaling was activated and required for the hair follicle inductivity in adult fibroblasts. Finally, we searched for key protein factors to elicit hair follicle neogenesis. Through proteomics analysis with mass spectrometry, we identified 3 extracellular proteins enriched in embryonic skin that together were required and sufficient to induce hair follicle neogenesis in vivo. Therefore, organ regeneration could be initiated by creating a pro-regeneration environment with defined extracellular factors. Identification of such environmental signals can be incorporated with other approaches to enhance tissue regeneration.

damn HF neogenesis in a full thickness wound without DP cells or newborn dermal cells, it sounds huge!

[lacazette]

And now from a few days ago:

http://otl.sinica.edu.tw/en/index.php?t=9&group_id=24&article_id=858

Home -> Technologies Available

Preparation of skin extract for hair follicle neogenesis

Docket Number：03A-1031215

Inventor：Sung-Jan Lin, Mai-Yi Fan, Yu-Ju Chen, Chia-Feng Tsai

IP Status：US pending, TW pending

Abstract：

When skin is wounded, it tends to repair with fibrosis without regeneration of associated appendages. To regenerate functional skin, we hypothesized that skin appendage regeneration can be facilitated by defined extracellular factors. We screened and successfully identified protein extract and a ****tail of specific protein mixtures that are able to induce hair follicle neogenesis.

Fields of Application：

Protein extract or ****tail of specific proteins can be used in (A) As a drug for local administration to induce hair follicle neogenesis; (2) Preparation of bioartificial dermis or bioartificial skin: addition of the extract in bioartificial skin or bioartificial dermis can induce hair follicle neogenesis; (3) In vitro cell culture: addition of this recipe to cultured fibroblasts can confer the fibroblasts trichogenic capability.

Advantages when compared to the existing technologies：

With this technology, hair follicle neogenesis can be induced without expansion of hair follicle dermal papilla cells from the patients. The cost can be reduced.

[allTheGoodNamesAreTaken]

Another good find, but... mice.

[baldybald]

Another good find, but... mice.

And you may hear mice in the next 15 yeas, sorry.

[Mpbman]

Sometimes I wish I was a balding mouse

[lacazette]

it's been a decade that researchers are working to overcomed the large expansion of DP cells and maintenance of their hair-inductive capability (why aderans crashed)

Now sung jan lin is able to induce HF without DP cells! Just with fibroblasts cultured in the right protein extract. If it's the case it's a game changer

And remember this SJ Lin trial in taiwan hospital with 400 people beginned in 2006 ( estimation date 2016)

https://clinicaltrials.gov/ct2/show/NCT00506636?term=hair+follicle&rank=3

"This study is to try to maintain cultured dermal papilla cells in spherical structure in vitro before transplanting into dermis in vivo. Also, this study is aimed in clarifying actual mechanism of inducing hair follicle by dermal papilla cells."

This guy want to cure hairloss, he dedicated his life to it , more of one decade studies all in the hair follicle area
He is/will plan for sure to test this new technique (without the need of DP cells) soon I think, if it's not already planned.
could be a safely and simply protocol like aderans (not w/ DP but Fibroblasts cultured cells) but with the efficiency? Or a wound neogenesis protocol with direct application of the protein extract as he claim on his invention? I don't know but I believe in this guy, he's a smart little genius since his teens, look at his parcours

[Renee]

Everything is pre clinical research stage.

[hellouser]

it's been a decade that researchers are working to overcomed the large expansion of DP cells and maintenance of their hair-inductive capability (why aderans crashed)

Now sung jan lin is able to induce HF without DP cells! Just with fibroblasts cultured in the right protein extract. If it's the case it's a game changer

And remember this SJ Lin trial in taiwan hospital with 400 people beginned in 2006 ( estimation date 2016)

https://clinicaltrials.gov/ct2/show/NCT00506636?term=hair+follicle&rank=3

"This study is to try to maintain cultured dermal papilla cells in spherical structure in vitro before transplanting into dermis in vivo. Also, this study is aimed in clarifying actual mechanism of inducing hair follicle by dermal papilla cells."

This guy want to cure hairloss, he dedicated his life to it , more of one decade studies all in the hair follicle area
He is/will plan for sure to test this new technique (without the need of DP cells) soon I think, if it's not already planned.
could be a safely and simply protocol like aderans (not w/ DP but Fibroblasts cultured cells) but with the efficiency? Or a wound neogenesis protocol with direct application of the protein extract as he claim on his invention? I don't know but I believe in this guy, he's a smart little genius since his teens, look at his parcours

Fibroblasts? Would that be FGF-9? If so, thats been known for a while thanks to Dr. Cotsarelis. Was even talked about on the Spencers radio show with that regular caller of his....joefromstantonisland or whatever.

[lacazette]

Fibroblasts? Would that be FGF-9? If so, thats been known for a while thanks to Dr. Cotsarelis. Was even talked about on the Spencers radio show with that regular caller of his....joefromstantonisland or whatever.

Nope Fibroblasts are cells (that can be taken from our skin and cultured far more easily than DP cells, in larger proportions,etc - if i remember well, i have to look again about that)

FGF9 and others are just growth factors of these cells


"A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen
The main function of fibroblasts is to maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix. Fibroblasts secrete the precursors of all the components of the extracellular matrix, primarily the ground substance and a variety of fibers. The composition of the extracellular matrix determines the physical properties of connective tissues.

"Fibroblast growth factors, or FGFs, are a family of growth factors.The FGFs are heparin-binding proteins and interactions with cell-surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction"

[nameless]

so now they can produce hair induced DP cells by way of fibroblasts and by way of iPS cells.

This means that the issue of hair inductivity is solved. Now it's just a matter of running these techniques through trials. This should take 3 years in Japan if they don't have to do animal studies.

[englishman]

lacazette is this new exploring or founding really a step forward? I am just asking because I am not an expert at this particular matter ,so please dont mind

[joachim]

in other words, i think, this scientist also just found out that wounding plus a specific protein coc.ktail lets the fibroblast skin cells turn into DP cells and therefore form hair follicles. or have i misunderstood that?
it could be that this scientist is a bit ahead of cotsarelis as it says they identified the 3 most important proteins for performing that task. they found it out by tinkering around with embryonic skin cells.
cotsarelis was always talking about FGF9 but i don't remember if he mentioned other proteins as well.

it is good that there is a second team which figured out which proteins are crucial. that creates pressure on follica.
do we have more infos about that research or study? could it even be replicated by others?

man, that wounding approach sounds soooo attractive. it could be so easy if we knew the exact protocol. this could create hair in a matter of weeks, and almost naturally without serious side effects. i also think that growth direction would be no problem. i have a feeling that the cells will find the right direction on their own, more or less. or maybe the wounding device (needle or laser) will guide the cells by the way and angle the wound is created.

did anybody else understood it this way, or am i wrong with the assumption that this is similar to cots' wounding approach?

[Renee]

Lack of Collagen VI Promotes Wound-Induced Hair Growth.

Collagen VI is an extracellular matrix molecule that is abundantly expressed in the skin. However, the role of collagen VI in hair follicle growth is unknown. Here, we show that collagen VI is strongly deposited in hair follicles, and is markedly upregulated by skin wounding. Lack of collagen VI in Col6a1(-/-) mice delays hair cycling and growth under physiological conditions, but promotes wound-induced hair regrowth without affecting skin regeneration. Conversely, addition of purified collagen VI rescues the abnormal wound-induced hair regrowth in Col6a1(-/-) mice. Mechanistic studies revealed that the increased wound-induced hair regrowth of Col6a1(-/-) mice is triggered by activation of the Wnt/β-catenin signaling pathway, and is abolished by inhibition of this pathway. These findings highlight the essential relationships between extracellular matrix (ECM) and hair follicle regeneration, and suggest that collagen VI could be a potential therapeutic target for hair loss and other skin-related diseases.

[mlamber5]

This thread has some very interesting reads. Although this has been pointing out countless times and is the most obvious of statements it is important to remember that while similar; mice do have a somewhat different skin environment. They have an abundance of g/d t helper cells, while humans have much less. Not only that, humans g/d t helper cells are located primarily along the blood vessels, unlike the mice. It is amazing they are finding all of these different things that help hair growth, but remember our skin environment is different. So I wouldn't get overly excited about something like this yet. That being said, I believe that in the future the best shot AGA suffers will have at turning a high NW back to a really low NW is going to be via wounding and and growth factors/environmental regulators.

[lacazette]

@englishman, no problem dude No for the moment I wouldn't say that it could be a step forward, we have to wait more. But it could be definitly exciting as this 'protocol' is safe unlike iPS cells with risks of dna mutations, tumors formations,etc
And as Mlamber pointed out, something can work in mice but not in human. Though they mention that the technology is now available for use to induce HF in bioengineered skin, or to replace human DP culture etc so I think it's not a problem in this case


Yes Joachim I undestood it like that too As he explained it could definitly be used after a wounding procedure to induce HF:

" regeneration can be facilitated by defined extracellular factors. We screened and successfully identified protein extract and a ****tail of specific protein mixtures that are able to induce hair follicle neogenesis."

"can be used in (A) As a drug for local administration to induce hair follicle neogenesis; "

I don't know what ****tail they succesfully screened, but it seems like THE powerful combination to achieve HF neogenesis (unlike the only FGF9 factor found by Cotsarelis)

So it seems it could work with a protocol like Follica, but not only!

-(2) Preparation of bioartificial dermis or bioartificial skin: addition of the extract in bioartificial skin or bioartificial dermis can induce hair follicle neogenesis;

So a possibility would be induce HF neogenesis in 3D scaffolds,etc, grow hair or hair germ on the bioskin before transplanted on us. ( like US army induced HF neogenesis and grow functionnal hair on bioskin)

-(3) In vitro cell culture: addition of this recipe to cultured fibroblasts can confer the fibroblasts trichogenic capability.

This one would be a simple cellular therapy like aderans tried with DP cells.
Culture fibroblasts ( that are easily taken from a skin biopsie) with the ****tail and then inject them where we want.
He say Fibroblasts with the protein exctract can induce HF in a full thickness wound, so it could be good

But if it's not sufficient,I think about something. The problem with DP cells was that the more they are cultured, the more they loose their inductive capacity.
But now what about induced HF neogenesis with the cultured fibroblasts/****tail, and then add the cultured DP cells in the already induced HF? The cultured DP cells wouldn't need anymore to keep their neogenesis inductive capacity, and would just make their job since injected to grow hair
Well the SJ lin protocol induce HF neogenesis, so that would mean that DP cells are created I think, but maybe in not a sufficient amount to grow a real hair, so in this case the simple solution would be to add cultured DP cells ( as long as they do'nt need to keep their inductivity, it solved the aderans problems )

So IMO this SJ LIN fibroblasts/****tail protocol could open doors for a treatment in different ways: wound neogenesis, 3D hair in vitro, or cellular injection

what is make me hopeful is also that quote :With this technology, hair follicle neogenesis can be induced without expansion of hair follicle dermal papilla cells from the patients.

And if you put in perspective with that previous human trial of SJ LIN in Taiwan hospital with 400 subjects:

https://clinicaltrials.gov/ct2/show/study/NCT00506636?term=hair+follicle&rank=3

Tissue Engineering for Hair Follicle Regeneration

This study is to try to maintain cultured dermal papilla cells in spherical structure in vitro before transplanting into dermis in vivo. Also, this study is aimed in clarifying actual mechanism of inducing hair follicle by dermal papilla cells.

Hair transplantation is an well-documented way of treating hair loss. Hair transplantation is based on redistribution of hair follicles without any new follicle formation. It has been long that a lot of researchers have focused on developing skills in regenerating hair follicles. However, cultured dermal papilla cells lose the ability of inducing hair follicle formation after several generations in vitro culture. Our study is aiming in culturing dermal papilla cells in vitro and maintain their spherical structure before transplanting into dermis in vivo. Meantime, this study may help clarify the actual mechanism of inducing hair follicle by dermal papilla cells.


So he tried with DP cells, so i'm quite confident he will try with his new found. maybe like above with 3D hair in vitro that are then transplanted. Or maybe with a wound neogenesis protocol or a cellular therapy as he mentionned aswell

I'll try to contact him and the taiwain hospital, see if they answer something
Any tawainese guy here to wait in front of his lab door?^^