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

[Desmond84]

OK guys, so after reading over 300 research papers on hair follicle and embryo development for 12 months, I've come to realise the only reason why we are still in this mess is only for one reason and that is:

"WE CAN NOT EXPAND DP CELLS IN CULTURE"

That is what's holding Tsuji team back, making Lauster lose interest, forcing Aderans & Intercytex to call it quits and keeping us bald!

We need the entire community and the research field to put all their focus on this problem!

In the Tsuji study for example, they had fully functional DP cells and epithelial stem cell. They simply placed them on top of each other and voila, hairs started forming immediately. We can expand epithelial stem cells in culture, but NOT DP cells...

We hear time and time again, conspiracy theories about Big Pharma holding out on the cure or the society wanting us to stay bald...BUT that is not true. The fact of the matter is, we are stuck on one final step (a crucial step)...Once we figure it out, the rest of the way has been paved for us by groups like Tsuji team and Lauster!

So, here's a small request to our great community. Read research papers. Discuss ideas of how we can go about this problem. Brain storm. And one day, either us or the scientists will figure it out.

You guys might not believe it...but the cure is that simple. Multiply fully functional DP cells and MPB will be a fashion statement.

[Desmond84]

This involves more of us (specially those in their early 20's) taking up degrees in Bachelor of Biotechnology, Developmental studies, and Biomedical Sciences.

We need to experiment with state of the art 3D scaffolds, growth factors, etc!

The "first dermal signal" believed to be responsible for development of DP cells in the embryo is still unknown! Finding out what molecules make up this signal may hold the key to expansion of DP cells in culture! There are some indications that Beta-catenin may be one of these first signals! Maybe we should incorporate this signal when we culture DP cells.

We need crowdfunding ideas to support Jahoda, Christiano and Cotsarelis.

If we want to see a cure in our lifetime, we need to work for it...period.

We should think of it as an investment for our future.

We need to make this thread sticky! Everyday we have more ppl realising they suffer from MPB and join this community. We need everyone to understand why there is still no cure and how can we solve it with one simple breakthrough.

[garethbale]

Hey Desmond

Thanks for the info.

Have you communicated your thoughts to any of the people looking in to cellular treatments for hair loss (Replicel, Tsuji etc)? I would have thought all thier scientists and researchers are aware of what you had suggested but I was just wondering if you's queried this with them and what their response to you was, if any.

I like your optimism about crowdfunding a project and would definitely get involved if it happened. I know Aderans parent company invested $100 million or so in, but I don't think this specifically went into Aderans Research and consequentially to Ji Gami funding. Companies such as Replicel, Histogen etc really don't have that much available cash.

[youngin]

https://www.youtube.com/watch?v=mfLLkmY_t9k So you're saying they lied in this video? Cause that's exactly what she said. They expanded dp cells in a 3d spheroid culture and they were inductive. Did you read Jahodas study? This is what NIGAM is doing right now.

[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

[baldozer]

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

[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!

[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]

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!

[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]

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!

[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

[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]

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."

[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.