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

[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.

[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...

[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?

[NeedHairASAP]

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

could somebody maybe add them here?

[Thinning87]

The truth guys is that unless there's a miracle, we will barely have anything new in 2020. If things go somewhat well, we might have histogen by 2020 to grow some hair on those of us who will have any left.

Replicel might pull it off but honestly they had very poor data as you all know.

Follica who knows, but it looks like they will stay quiet for a while again now.

All the rest including Jahoda and tsuji is a long time away

I'm just glad I shaved in February and was able to accept my self. At least I wasn't thinking about hiding my thinning hair back then.

[Desmond84]

Here's another idea:

"We know that embryonic and foetal skin can repair itself without any scarring + with 100% hair regeneration when damaged"

"Histogen believeded the reason for this rapid tissue recovery is the hypoxic conditions the foetal tissue exists in. SO they cultured fibroblast cells in hypoxic conditions (3% O2) and the fibroblasts went crazy! They started upregulating over 5000 genes and mass-producing growth factors that are vital to skin and hair repair!"

So, now lets look at DP cells. They are known as "Fibroblast-like" cells with some multipotent properties. SO why don't we try and culture DP cells in HYPOXIC conditions using Jahoda's scaffold?

Could this increase inductive potential of DP? We need to put all these ideas together and send it off to Jahoda & Christiano!

I was thinking about that driving home from work What do you guys think?

[Desmond84]

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.

Yeah but Arashi, the trick is to know how to go from iPS cells to a specific cell line. Some we have figured out but most we are still puzzled on...DP cells being one of them.

iPS cells are definitely a new and radical approach to tackle this problem BUT we should also try the former as it may prove to be safer at least in the short run (as you stated )

[Desmond84]

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,

Very good question indeed. The purpose of growing human DP cells in spheroids was explained very well in the study. Here's their explanation:

"One striking difference between the behavior of human scalp dermal papilla cells and those of rodent vibrissa follicles is their propensity and capacity to aggregate both in vitro and in vivo.

Indeed, this intriguing cell-autonomous property is observed in cultured rat dermal papilla cells after subdermal injection, suggesting that they maintain their identity even after they are transplanted in the absence of epidermal contact. The cultured rat dermal papilla cells self-aggregate within the dermis, adopting embryonic-like properties, and form a papillae condensate-like clump that synthesizes its own extracellular matrix (20). However, we have never observed spontaneous aggregation in cultured human dermal papilla cells injected into skin, highlighting species-specific differences related to self-aggregative behavior.

Intriguingly, these observations invite a different strategy for achieving the necessary first step toward human hair follicle neogenesis, i.e., promoting cultured human dermal papilla cells to undergo self-aggregation.

We show here that, by creating the microenvironment for self-aggregation by culturing dermal papilla cells in hanging drop cultures, we establish dermal spheroids that physiologically mimic cell condensations. Creating 3D spheroids partially restored the intact dermal papilla gene-expression signature within the cells and, in turn, their associated hair-inducing properties.

Microsurgical implantation of dermal spheroids in a unique human skin induction assay enabled us to demonstrate that the establishment of dermal papilla cells in spheroids is, in itself, sufficient to partially restore inductive properties to cultured dermal papilla cells."

but what are the so called growth factors?

Growth factors are biological signals telling the cells how to behave in different conditions. Here's two excerpts from the study:

"Sebaceous glands were not seen in follicles created after spheroid transplantation whereas these glands were detected in follicles induced by transplanted intact dermal papillae."

"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."


The paracrine signals they mention is growth factors and other molecules that we may need to add to the culture medium to maintain DP cells inductivity. Unfortunately however, they did not test any growth factors in their culturing medium. This will be in their next study most probably.

Also I came across this article published in 2009.:

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

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?

Very good find brother I'm gonna read this further...unfortunately they were only testing their spheroid technique and didn't attempt at testing the effects of different growth factors and proteins on their DP cells!

[Desmond84]

Here's the reason why I think solving the DP culturing problem will bring about hair multiplication almost instantly. This is directly out of Jahoda's latest published study:

"Sebaceous glands were not seen in follicles created after spheroid transplantation whereas these glands were detected in follicles induced by transplanted intact dermal papillae."

So, the cultured DP cells (with 22% genetic signature) couldn't form sebaceous glands whereas the original donor DP cells that were expressing all their genetic signatures managed to form sebaceous glands in every instance!

So guys, it's really that simple! We perfect our culturing technique and every single DP 'spheroid' will yield a terminal hair follicle. Period.

[sdsurfin]

DP cells

I'm not a scientist, but it seems to me that an effective route might be, as desmond stated, to find out what genes are making mouse DP cells multiply easily, and holding ours back. This does not seem like an impossible task. Another approach could be to compare the genetics of several different DP cells from animals, different parts of the human body,etc, to see what makes them tick. What about looking at monkey DP cells? I'm surprised that baldness research does not utilize an animal that is closer to us genetically. I'm not really into harmful research on animals, but if all you're doing is taking some hair cells from them it shouldn't be a big deal. I'm sure they've got a surplus of monkeys running around in india. This is probably a totally crazy idea, but seeing as jahoda was able to clone his hair on his wife's arm, what about using DP cells from monkeys? I understand that the body rejects foreign cells, but might there be some way to reprogram DP cells that have a greater multiplication capacity in a way that makes them acceptable by our body? Mice seem to be a stretch, their DNA is so different, but what about chimps?


Maybe in comparing the DP cells of mice to those of monkeys to those of humans some clue might be found. From my understanding, what we have going now as opposed to twenty years ago, is the technological power to process and record the genetic codes and patterns that everything has, and computers that can make sense of patterns and vast numerical information. I'm surprised that more effort isn't being put into decoding the genetics of hair cells as opposed to trying to figure out how to clump them together. Gene therapy on one type of cell seems much more plausible than gene therapy on a scalp, with everything it has going on.


Another question fro desmond or anyone that knows: Do DP cells from say, our leg or arm, behave in the same way as scalp DP cells? Has anyone tried to culture cody DP cells? If those act differently that might be another route to finding why scalp DP cells act the way that they do.

[Desmond84]

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

could somebody maybe add them here?

Yes I have. He's a great poster indeed with a great insight! Everyone should read his post as he has been around long enough to know all these studies back to front. Here's the bulk of his post for those that haven't read it:

"It's sounds like you're making broadly general statements based on limited knowledge."

Yawn, back when you were in your mother's womb, and I was having direct conversations with guys like Stenn and Jahoda, I realized Jahoda would never be able to bring this research to fruition because he lacks the experience and skills necessary to accomplish this.

Look, I'm not telling you anything here anyone that is familiar with Jahoda's research doesn't already know. Jahoda freely admits this and even talked about it in an interview today.

COLIN JAHODA: "For me it's more of a proof of principle thing in the sense that someone had to show that we could do this multiplication step. The next stage is really to, you know, cosmetically, people are only going to be happy with a follicle that grows hair that's the right length, the right color, grows in the right direction etc, so you know there's a whole secondary step that has to be taken.

SOME OF THEM ARE ALMOST KIND OF ALMOST ENGINEERING PROBLEMS THAT ARE NOT REALLY MY SCIENCE. BUT WHAT IT WILL DO IS IT WILL SPARK A LOT OF INTEREST IN PEOPLE WHO ARE TRYING TO DO THIS KIND OF THING TO TAKE IT FORWARD, I THINK."

http://www.abc.net.au/am/content/2013/s3873945.htm

So although, you might not like what I said, and you might want to get me to take it back, I can't take back the truth and replace it with a lie in an attempt to provide you with false hope.

"James, you've written thousands of words about Dr. Gho, praising him, defending him, implying that he's found the "cure" based on "HM" and that he and he alone knows/knew what it was, you don't say a single word about him now."

That's not true. I praised Gho for being in the forefront of the science and felt at the time that he was the researcher who was best positioned to bring hair multiplication to fruition. It's important to realize, I was not a one trick pony back in those days. I was also having direct conversations with Kemp, Jahoda, Kim, and many others. This helped me to realize that Gho truly was in the lead. Since that time, me, you, and many others subsequently put our faith in ICX, Aderans, etc. Unfortunately, these guys simply ended up duplicating Gho's earlier research and wound up failing at the exact same stage(consistency issues). Are you now claiming that you did not hype Aderans and knew all along it would end in failure?

Next up, Kevin McElwee, who I also corresponded with a time or two back in the day. Interestingly, I got less information and enthusiasm from him than any other researcher I contacted (including Jahoda). Not that his ongoing research effort will end in failure. But nearest I can tell, his current effort is very similar to what the rest have already tried before. Unless he has added something dramatically new that he is hiding from public eye, there is a very strong chance he will end up where the others who came before him did. Can you supply a valid argument to the contrary?

Guys like Nigam come along, hype themselves, say a couple of buzzwords, and get people to believe they are right around the corner from a cure. And all it takes to gain a hoard of groupies is to use the same old photo and lighting techniques that hair transplant clinics have used for ages.

I say what I say not because I'm uninformed on the subject matter. I say it because I've already been here, I've already seen this, and I've already done this. The tricks that fool you into believing you are looking at a brand new car appear to me to be the same old car disguised behind a brand new paint job.

"If these are "dark days" of Hair Multiplication, then how did we get here, if Gho had the secret all along?"

Once again, Gho foresaw the future and performed these experiments well out in front of the rest of the world. Unfortunately, he couldn't figure out the consistency problem, and he failed. Seeing others follow down the exact same path and end up failing, it's obvious this is par for the course. If anything, it supports my earlier claim that we have reached the dark days of hair multiplication.

You ask who has ever done what Jahoda has done? I'm surprised you asked, because you already know the answer. In order to explain this, let's look at how Jahoda describes this new breakthrough:


COLIN JAHODA: "What we've done differently here is taken a small bit of the follicle, small bit of tissue, multiplying out the cells in that tissue. But when you put that into the skin, that structure interacts with the environment and creates a new, completely new, follicle."

Like I said, same old car disguised behind a brand new paint job.

"Please, let's give Jahoda and Christiano some credit for trying this, expanding the scope of research, and pursuing these ideas. Don't you think they know about what Aderans' successes and failures were?"

No they do not know about Aderans' successes and failures. That's exactly my point. They are speaking from what has been done in academia. This is a very different world from what has occurred in the private sector. Let's see, Jahoda's funding way under $1 million. Aderans' funding $150 million.

I stand by my earlier statements. But please don't confuse this with me claiming that hair multiplication is dead. As Dr. Paul Kemp, current CSO of Intercytex pointed out, in advancing new treatments, after much initial enthusiasm, the industry reaches a lull where people give up on the idea. Eventually, a new generation rises up with a crop of new ideas and brings forth the cure.

We are currently in the lull. If you don't think so, tell me who has $150 million more dollars to see this treatment to fruition? The answer is, these are the dark days of hair multiplication.

Bruno Bald asked: "So your saying Dr. Jahoda is doing the same stuff Adreans did 10 years or so ago and there is nothing new about Jahoda findings at all?"

Not exactly. There are minor aspects of the research that are not available elsewhere in the public literature, and in that sense it is interesting.

But as far as a novel cure for baldness is concerned, in 1998 Tom Barrows seeded DP cells into a 3d matrix, implanted this into a human scalp at the dermal-epidermal junction, and grew new hair follicles. After a stint at Aderans Research where he was unable to turn this research into a viable treatment, he is still trying to perfect the technique using a more modernized approach.

http://bmeminions.wordpress.com/2013/09/30/tom-barrows-cso-cell-constructs-are-you-ready-to-face-the-brave-new-world/

In short, Oliver was one of the original pioneers of this research. Jahoda was his understudy and performed the necessary fundamental research to inspire others, and these others have since furthered the research beyond where Jahoda has been. Since this research has occurred in the private sector, it isn't common knowledge to many.

The big take away from Jahoda's latest study is DP cells lose their ability to create hair follicles when cultured. I first spoke to Dr. Kim many years ago about this problem and the cDNA microarray work he had done while attempting to address this issue. Sometime later, Gho told me he had ran into the issue and given up on this cell type. Later, Jahoda was surprised when he implanted these cells in his wife's arm and they didn't result in hair growth.

Understanding this has represented one of the big limitations to performing a consistently viable hair restoration treatment, Jahoda has followed up on his earlier research in rats where he discovered culturing DP cells in 3D leads to an increase in their hair producing ability. So he used a modern 3D culturing approach to show that DP cells can indeed grow new follicles in human skin. It's important to note, Jahada's cultured cells only had 22 percent of the gene expression of healthy DP cells, so there is still much work to be done (I.E. Jahoda's technique only resulted in partial restoration of the cells' hair producing ability).

This is not revelational to hair multiplication researchers, but makes for an interesting experiment and news tidbit. I had a conversation about this subject with Kurt Stenn quite a few years back. It's well known stuff among researchers.

[thechamp]

Yes I have. He's a great poster indeed with a great insight! Everyone should read his post as he has been around long enough to know all these studies back to front. Here's the bulk of his post for those that haven't read it:



Bruno Bald asked: "So your saying Dr. Jahoda is doing the same stuff Adreans did 10 years or so ago and there is nothing new about Jahoda findings at all?"

Hey Desmond your research is great I just wanted to say hello from Perth Australia where in Australia are you!

[Desmond84]

Hey Champ Are you from Oz? Wow brother...I'm from Sydney

[thechamp]

Hey Champ Are you from Oz? Wow brother...I'm from Sydney

Yeh man from Perth I saw something you posted last week I think it was the seven pm project you where talking about ,how's life in Sydney ? Perths nice the weather is always great!

[garethbale]

Yeh man from Perth I saw something you posted last week I think it was the seven pm project you where talking about ,how's life in Sydney ? Perths nice the weather is always great!

My mate moved to Perth and he says it's ridiculously expensive