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

[NeedHairASAP]

Hey desmond have you seen James Bond's recent posts?

could somebody maybe add them here?

[Sogeking]

Okay guys I am obviously lacking in terms of knowledge of hair follicle parts, biological interactions and so on.
However Des, I agree with you. The recent findings of Jahoda and Dr. Cristiano told us how far they still are.

So I have some questions. Basically how do spheroids make the DP cells multiply? You take DP cells, from the base of the hair, you insert them into this spherical culture, but what are the so called growth factors? AS fr the lack of the sebaceous glands, I thought that arrector pilli muscle serves the purpose of making the hair follicles "stand up", although sebaceous glands make the hair oily so it wouldn't become too brittle.


Also I came across this article published in 2009.:

http://www.ncbi.nlm.nih.gov/pubmed/19238412

Inhibition of glycogen synthase kinase-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1 in human primary dermal papilla cell culture and maintains mouse hair bulbs in organ culture.

It mentions the importance of FGF-2 as well. Although Cotsarelis's study says FGF-9 is used when forming hair follicles. So why not fgf-9 with dp cells when the spheroids are implanted in the skin.



Okay more subquestions. Which compounds or proteins were used for gene expression?

[Arashi]

Hmmm to answer my own question, I think Tsuji labs is looking at both possibilities, right ? I see they're talking about culturing the Epithelial and DP cells, but they're also talking about using investigating the use of iPS cells...

[Arashi]

Hi Desmond,

The thing I don't understand about all this: why does Tsuji lab need to culture DP cells ? The goal is to create epithelial and mesenchymal (derma papilla) cells from iPS cells right ? It's a different approach than Jahoda's (who is just culturing DP cells).

Thanks to recent findings, iPS cells now can be easily, quickly and safely expanded (though officially that's ofcourse yet to be proven with the currently running clinical trial). The challenge however that Tsuji is facing is getting those iPS cells to differentiate into epithelial and mesenchymal cells. What I understood from their research (but correct me if I'm wrong), is that once they've done THAT, then they're done, since the hair they created DID contain the right pigmentation etc.

[Desmond84]

So the last paragraph highlights two points:

1) We need to improve on this technique to achieve better DP signatures (above 22%)

2) We need to carry out more study to figure out the necessary signals and growth factors for the mesenchymal:epithelial interaction to achieve follicular neogenesis.

[Desmond84]

I agree that it can be frustrating to watch research progress at a snails pace.

Also, it's a shame that the full text of the paper is behind a pay-wall. I'm sure a lot of people outside of academic institutions with access would like to read it.

True. Well let's use this thread as a way to help ppl access some of the information in these research papers. Here's the important segments of Jahoda/Christiano study for you to read

"Spheroids formed readily by 24 h and were morphologically akin to intact dermal papilla (22). Per experiment, between 10 and 15 spheres were placed between separated foreskin epidermis and dermis, which was recombined and grafted onto SCID mice. Strikingly, after 6 wk, we observed de novo hair follicles (Fig. 3C) from five of the seven donors (Table S3, Fig. S2), which we confirmed were comprised of human cells using an antibody specific to human nuclei (Fig. 3D). On two occasions, unpigmented hair shafts were observed emerging from the skin that had been implanted with spheroids (Fig. 3E). Sebaceous glands were not seen in follicles created after spheroid transplantation whereas these glands were detected in follicles induced by transplanted intact dermal papillae."

"We were also able to visualize mouse blood-vessel formation, particularly around de novo follicles, indicating anastomosis with the graft"

"The longest duration of any graft in our study was 6 wk, and therefore long-term follicle function was not assessed. At this endpoint, the efficiency of inductivity varied between donors, ranging from 10% to 60%."

"Three-Dimensional Culture Partially Restores the Intact Dermal Papilla Signature. The average correlation coefficient between intact dermal papilla and cells at p3 was 0.42 (range: 0.39–0.44) whereas between intact papillae and spheroids it was 0.56 (range, 0.55–0.58)"

"The observation of hair follicles within grafts, as described above, suggests that the 22% restoration of papilla signature is sufficient for follicle neogenesis. However, as complete hair-follicle morphogenesis involves epithelial:mesenchymal interactions, it is likely that external paracrine signals will be required for full signature restoration and development of external hairs. Importantly, in this study, we have demonstrated that dermal spheroids are, by themselves, capable of initiating the hair induction process in non-hair-bearing human skin, where there are no previous epidermal “hair-follicle” signals."

[walrus]

Brother, I'm not playing it down. I wanna make sure their work continues! I want to see more ppl joining their team trying to improve this technique...This is the entire point of this thread...incremental improvement to this technique.

They've gone full throttle and made everyone aware of their research! My mum even watched it and told me about, which was very surprising to say the least!

But, I don't want to wait another 10 years for someone to come along and say "hey I think we can improve this"....I want the research to start now, because we all know how long it takes for new treatments to go through trials!

This thread is simply there to gather data about what might be the reason DP cells are such a pain to culture! and ways we can come up with to help Jahoda & Christiano to continue!

I agree that it can be frustrating to watch research progress at a snails pace.

Also, it's a shame that the full text of the paper is behind a pay-wall. I'm sure a lot of people outside of academic institutions with access would like to read it.

[Desmond84]

We must be objective in analysing data and understand what was still missing so we can improve on it!

As much as I love Tsuji's work, I have to admit all their technologies will be useless until DP cells are fully cultured...it's a fact.

And once we know the problems, we can move in the direction of solving them objectively...

We used to think 2014 was the year of Aderans. 2015 was Histogen. 2016 Replicel and cure will be here by 2020. But we were wrong! Some may say way off!

We need our younger generation of baldies to enrol in Biotechnology courses and show more enthusiasm towards developmental biology.

We need to work the problem from the grounds up. We need a large pool of researchers at our disposal before we discuss the funding issues. Right now, we have a handful of decent hair researchers...period.

I want ppl to read this thread and understand, Jahoda needs a new generation of bioengineers to help him with new ideas...

I want us to find the cure

- Des

[Desmond84]

Desmond, it seems that you are slightly playing down the recent achievement of Christiano and Jahoda at the beginning of this thread. Now that they have established proof of concept in humans (perhaps the most difficult step) - a base to work from - there is no reason that the figure of 22% gene expression can't be increased through further experimental refinement.

Brother, I'm not playing it down. I wanna make sure their work continues! I want to see more ppl joining their team trying to improve this technique...This is the entire point of this thread...incremental improvement to this technique.

They've gone full throttle and made everyone aware of their research! My mum even watched it and told me about, which was very surprising to say the least!

But, I don't want to wait another 10 years for someone to come along and say "hey I think we can improve this"....I want the research to start now, because we all know how long it takes for new treatments to go through trials!

This thread is simply there to gather data about what might be the reason DP cells are such a pain to culture! and ways we can come up with to help Jahoda & Christiano to continue!

[walrus]

Desmond, it seems that you are slightly playing down the recent achievement of Christiano and Jahoda at the beginning of this thread. Now that they have established proof of concept in humans (perhaps the most difficult step) - a base to work from - there is no reason that the figure of 22% gene expression can't be increased through further experimental refinement.

[Desmond84]

Here's one great idea we can test out using Crowdfunding money:

"Mice DP cells are easily cultured and they maintain 100% of their hair induction potential"

"Human DP cells on the other hand can not be easily cultured and so far we've only been able to restore 22% of their genetic expression by tricking the cells into thinking they are still in their stem cell niche by using a 3D scaffold"

Such major differences between two mammalian species may be explained via a genetic analysis test comparing genetic makeup of human and mice DP cells! It might be one single gene present in us that is inhibiting human DP cells from expanding in culture. Suppressing this gene may prove to be the only necessary step! You simply add the gene suppresor to the culture dish and watch the DP cells expand indefinitely as in mice DP cells...

A simple task yet no funding to do it!

[Desmond84]

Perhaps God wants us to stay bald! That is his evolutionary plan it seems !

LOL if God really exists, I'm sure he has much bigger things in mind than the suffering of man! The solutions to all these problems are there for us to find.

The blueprint is written somewhere in our donor zone and mice DP cells. We just have to keep looking

[Desmond84]

Hey guys, sorry for not being able to give an in-depth answer atm; I'm super busy.

With regards to Gareth's concerns: they actually know and have stated it several times. In their latest interview, they announced they are looking at the iPS cell option as a way to produce large numbers of DP cells. This has never been attempted and will be interesting to see how they go about achieving it.

Dr Cotsarelis was interviewed back in 2012 when Tsuji lab's hair regeneration paper was published. He was taken back at how efficient their method was but also stated that they haven't been able to prove hair multiplication, since they reconstituted DP cells extracted rather than expanding them in culture.

As for the Christiano/Jahoda study mentioned by Youngin; you are exactly right and this is the first step in the right direction, but there are many more steps needed. One shortcoming of their method is that the 3D scaffold only partially restored the hair follicle inductivity of the cultured DP cells. (DP cells only retained 22% of their gene expression characteristics!) This partial restoration of hair inductivity was enough to form de novo hair follicles, however, there were some shortcomings since 78% genes were no longer expressed. They were as follows:

- Only 2 out of the 7 implants emerged from the skin
- Sebaceous glands (sweat glands) did not form in any of the de novo follicles
- Melanocytes (pigmentation cells) did not form in any of the de novo follicles

This led to hairs that were non-pigmented and thin & whispy. The sweat duct attached to the sweat glands also helps direct hair follicle upwards allowing it to break through the skin. Lacking sebaceous glands is a major engineering problem!

All in all though we need incremental improvements to this technique by having several research teams working on it. If we can improve on this technique and restore somewhere around 90% of DP cells genetic expression in culture, we will have fully functional hair follicles formed with mature sebaceous glands and melanocytes attached to the hair shaft.

We need more work done in this field and we have to start ASAP or we will have to wait another 20 years for the stem cell arena to force feed the hair industry technology to improve on their DP culturing methodology.

We need ppl to stand up and take responsibility. Hellouser is right! Lets direct all our skillz in an organised fashion to move this project forward...it's not a one man job. We need everyone involved. I'm not an IT or visual arts person but I can be there helping with all the scientific jargon.

Lets get the ball rolling guys. If someone had told me 18 months ago, where I have to focus all my attention to cure baldness, I wouldn't have bothered reading all those irrelevant articles!

Now we know, what needs to be done...so let's do it!

[baldozer]

Perhaps God wants us to stay bald! That is his evolutionary plan it seems !

[hellouser]

Crowdfunding I am more than willing to spearhead but only if there's help. There was some good progress between myself and Axel a couple months ago but he's fallen off the map... so I've been stuck.

A little info about me: I'm a 10+ year veteran in graphic design, digital media, marketing and advertising. Anyone working with me would be in good hands... I just need collaboration and dedication. There's too much work to do on your own with this kind of initiative