Reason why there is still no cure in 2013 and the solution

[thechamp]

Champ If Tsuji lab is really working on this technique like I think they are, and the DP cells have actually maintained their inductive properties, I am more than certain they'll be ready for Phase 1 by 2016! With regulations changing in Japan regarding regenerative medicine, you might be able to have this therapy available by 2019 in Japan...

Well I hope there is better treatments before 2016 that's still 3 years away

[Desmond84]

Well I hope there is better treatments before 2016 that's still 3 years away

Histogen should become available somewhere in the world by 2016! CB-03-01 cream for acne should be out by then as well!

[clandestine]

Desmond, can you by chance email Jahoda, etc. about the 2012 discovery you've mentioned?

[walrus]

OMG GUYS

The Japanese cracked the DP culturing problem in 2012 (most of the culturing problems anyways)! Somehow we missed it!!!

We have to get Christiano/Jahoda to collaborate with Dr Ohyama of Keio Univerity! These guys figured out how to mimic the epidermis making DP cells believe they are still within the skin even though they were harvested!!!

Here's the study:

Restoration of the intrinsic properties of human dermal papilla in vitro

Manabu Ohyama*, Tetsuro Kobayashi, Takashi Sasaki, Atsushi Shimizu and Masayuki Amagai
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Accepted 1 May 2012
Journal of Cell Science 125, 4114–4125
2012. Published by The Company of Biologists Ltd
doi: 10.1242/jcs.105700

http://jcs.biologists.org/content/125/17/4114.full.pdf

Summary
The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of efficient isolation methods and the loss of innate characteristics in vitro.

We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs.

We performed a ‘two-step’ microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-39-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium.

However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.

In summary, we have elucidated the molecular signature of intact human anagen DP cells. This guided the development of DPAC for the efficient in vitro expansion of human DP cells that retain their intrinsic properties. The present study sheds new light on the biological properties of human DP cells and implies a novel strategy for supplying sufficient functional human DP cells for the development of molecules acting on in vivo DPs or for regenerative medicine-based approaches to treat intractable hair loss disorders.

__________________________________________________ _______________

We are so much closer than we anticipated! We just have to make sure both teams are aware of each others work! We have to test the cultured Japanese DP cells on a foreskin grafted on a mice...if we get fully functional hair follicles...the entire balding community can celebrate. Because ladies and gentlemen, this curse is over!

I am more than certain, Tsuji lab is aware of these recent developments and I can guarantee you they are testing these DP cells in their labs as we speak

VERY nice find Desmond. Perhaps this method combined with Jahoda's 3D culture approach would do the trick. The only thing this paper did not do was test it in human tissue, right?

[walrus]

As an application of the results obtained above, we attempted to
develop a culture medium that allows human DP cell expansion
while sustaining intrinsic properties, including the molecular
signature. Because the bioinformatics analysis implied the
involvement of WNT, BMP, and FGF signaling pathways in
the maintenance of human DP properties, we anticipated that
stimulation of these pathways during culture would improve the
biological characteristics of cultured DP cells. To test this
hypothesis, 6-bromoindirubin-39-oxime (BIO), recombinant
BMP2 (rBMP), and basic FGF (bFGF) were individually added
to conventionally used 10% FBS–DMEM to stimulate the WNT,
BMP, and FGF pathways, respectively.

[walrus]

An in vivo hair induction assay was subsequently performed.
DP-like cell aggregates were generated from dpacDP P1 or cDP P1 cells and placed between enzymatically separated afollicular murine
sole epidermis and dermis. The ‘sandwich’ composites were then
inserted subcutaneously into immunodeficient mice (Fig. 6C).
Intriguingly, developments suggestive of hair morphogenesis,
including epidermal invagination or papillary mesenchymal body
formation (Osada and Kobayashi, 2000; Osada et al., 2009)
(Fig. 6D), were observed in 9 of 21 mice in the DPAC-treated
group, but only in 2 of 18 mice in the control group (P,0.05). These
developments were surrounded by dermal cells positive for ALP and
human-specific vimentin staining (Fig. 6D,E), suggesting that they
were induced by transplanted human DP cells.

- Positive signs then, but no actual hair growth.

[clandestine]

Desmond do to think we could contact Jahoda, etc. about this 2012 discovery?

[Arashi]

Awesome find Desmond !! You're a true gem to the forum.

[Arashi]

Desmond, I always had the idea that the key to speeding up research was to make current reseach more accessible. After seeing how many publications were revealed during that conference in Edinburgh I realized there are hundreds, maybe even thousands of highly skilled researchers working on the problem worldwide. What if we could bring them together somehow and bundle all important publications for example or maybe even create a forum where they can discuss ? I do think the key is bringing knowledge together and make it accessible to them. What do you reckon ? Or do you think it's not a problem and that they already have some kind of platform or ways to follow the important developments ? I imagine conferences are good for that but by far not all researchers will attend. But I also imagine keep track of all developments currently is pretty much a dayjob by itself, which might become WAY more efficient with some good platform.

[MackJames]

Champ If Tsuji lab is really working on this technique like I think they are, and the DP cells have actually maintained their inductive properties, I am more than certain they'll be ready for Phase 1 by 2016! With regulations changing in Japan regarding regenerative medicine, you might be able to have this therapy available by 2019 in Japan...

Lets not forget, we were expecting Tsuji sometimes after 2022-2023! This is great news

Is the failure to properly culture DP Cup cells with active properties one of the reason replicel has less than stellar results?

[sdsurfin]

hmm

Desmond I like your posts dude, but you're also prone to some pretty intense speculation. It makes no sense to assume things like you do about tsuji experimenting with DP cells (why don't you email them and jahoda??), or if this is even the issue in curing baldness. I'm guessing hair loss researchers are aware of the research that's been done before, and know what the problems and hurdles are. To guess that they will start trials in 2016 is completely speculative. That being said, since you clearly spend a ton of time thinking about this, why don't you spend more time trying to contact the top researchers or trying to intern for them or something of the sort. They might even give you a paying job to do paper research. Or just create that job for yourself via a nonprofit company or whatever. I suggest you start a blog with all the insights you've come to, and share that with all the researchers you can find. maybe they missed something and will find it useful.

You're clearly a smart guy and spending time making speculative and hopeful posts on here is kind of a waste. I bet if for every time you posted on here you spent the equal amount of time studying to become a biologist or studying business to start a nonprofit or research venture for hairloss or whatever, it would be of much more service. It's refreshing to read your posts because they arent just whining about something or making random guesses at cures, but I feel like with the effort and knowledge you have, you should be out working for one of these researchers. Maybe even in Japan, it would be good to have some eyes over there.

Also, I emailed the company that's developing CB in the states, and they told me the acne cream will not be effective for hair loss, as the dosage and vehicle used are very different. So when it comes out don't start rubbing that stuff on your dome guys, it probably won't do shit. It's amazing the amount of time you can save by talking to someone who actually works in this business or is a doctor as opposed to trying to learn anything on a forum.

On a last note- my father is a cardiologist, and while they do have a database for research papers and keep up with things very often, it's definitely possible for doctors and scientists to miss information. I think it would be very easy to make a website or blog or something that has all the pertinent and interesting bits of research that people like desmond have collected, and then share that with all the people doing hair loss research. might be one of the few useful things that forum members could do with their time.

OMG GUYS

The Japanese cracked the DP culturing problem in 2012 (most of the culturing problems anyways)! Somehow we missed it!!!

We have to get Christiano/Jahoda to collaborate with Dr Ohyama of Keio Univerity! These guys figured out how to mimic the epidermis making DP cells believe they are still within the skin even though they were harvested!!!

Here's the study:

Restoration of the intrinsic properties of human dermal papilla in vitro

Manabu Ohyama*, Tetsuro Kobayashi, Takashi Sasaki, Atsushi Shimizu and Masayuki Amagai
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Accepted 1 May 2012
Journal of Cell Science 125, 4114–4125
2012. Published by The Company of Biologists Ltd
doi: 10.1242/jcs.105700

http://jcs.biologists.org/content/125/17/4114.full.pdf

Summary
The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of efficient isolation methods and the loss of innate characteristics in vitro.

We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs.

We performed a ‘two-step’ microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-39-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium.

However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.

In summary, we have elucidated the molecular signature of intact human anagen DP cells. This guided the development of DPAC for the efficient in vitro expansion of human DP cells that retain their intrinsic properties. The present study sheds new light on the biological properties of human DP cells and implies a novel strategy for supplying sufficient functional human DP cells for the development of molecules acting on in vivo DPs or for regenerative medicine-based approaches to treat intractable hair loss disorders.

__________________________________________________ _______________

We are so much closer than we anticipated! We just have to make sure both teams are aware of each others work! We have to test the cultured Japanese DP cells on a foreskin grafted on a mice...if we get fully functional hair follicles...the entire balding community can celebrate. Because ladies and gentlemen, this curse is over!

I am more than certain, Tsuji lab is aware of these recent developments and I can guarantee you they are testing these DP cells in their labs as we speak

[Dan26]

@sdsurfin

You are right in that there needs to be more effort to contact and colloberate with some of the researchers...if knowledege/ideas coudl all be shared and interconnected things would move along faster

Try and ask the cosmo dudes their vehicle for CB with hairloss....sucks it is gonna be trialed at 5% that is high and expensive to get right now on the grey market

[Pentarou]

Awesome find Desmond !! You're a true gem to the forum.

Word.

[Tomb10]

But are we al bit closer by the cure than 5-10 years ago?
- The hair on the mouse are really thin and nobody knows or is will work on the scalp of bald human.
- is it allready possible to create ten thousands of hairs when you start with 200?
- and then the other problems like density, good angle, collor, structure and most important that the hair will always remain. How do you guys think about this?

they have done over 30 years to clone a hair on a mouse, then we can't assume that in 10 years there will be a solution for us.

or am i the idiot?

[Sogeking]

But are we al bit closer by the cure than 5-10 years ago?
- The hair on the mouse are really thin and nobody knows or is will work on the scalp of bald human.
- is it allready possible to create ten thousands of hairs when you start with 200?
- and then the other problems like density, good angle, collor, structure and most important that the hair will always remain. How do you guys think about this?

they have done over 30 years to clone a hair on a mouse, then we can't assume that in 10 years there will be a solution for us.

or am i the idiot?

I just think it is ridiculous that in 2015. Toyota is going to deliver fuel cell based vehicle on to the market based on hydrogen fuel cells. I never thought I would see such a vehicle in this decade. Sure the way we can get hydrogen does not make it cost effective but still, the technology for making a car that runs on it, IS.

And here we are. The baldness front: zilch, zero, nada, nothing...

To answer some of your questions:

- is it allready possible to create ten thousands of hairs when you start with 200?

Current methods being researched by Dr. Christiano and Dr. Jahoda, also Tsuji Lab are based on taking your DP cells, then multiplying them and coaxing them with growth factors in these spheroids. So the number is not a problem. It is still a problem with hair transplants, of course.

- The hair on the mouse are really thin and nobody knows or is will work on the scalp of bald human.

The tests included human hair on mouses, and this artificial skin as well, so the hair itself will grow good.

- and then the other problems like density, good angle, color, structure and most important that the hair will always remain. How do you guys think about this?

Yup all problems still to be resolved. But these are why the research is still not done. In short, layman terms( I'm layman as well), we need something to coax this DP cells well enough so they could grow with sebaceous gland and arrector pilli muscle into a full blown hair follicle.
Time it will take us to do this? No clue, man. That is the depressing part. But you know life goes on. We'll have hydrogen fuel cars...