Q&A with Dr. Aaron Gardner

[sdsurfin]

Dr. gardener: what do you think of this? seems very applicable.


http://phys.org/news/2014-05-lab-stem-cells-key.html

[joachim]

dr. Gardner,

a theoretical question (because some questions and discussions about fat tissue and fat grafting came up):

when we extract a follicle from the donor site, there is also some fat tissue on it.
is it also possible to isolate and culture fat cells in dishes the same way you do it with the other cell types or is fatty tissue something special? is it even a tissue made of one cell type only or are there more cells in question?

[micgeed]

Dr. Gardner, I know your time is important. One quick ques: When this hair cloning procedure is finally available to the public. "Once this procedure is done on a patient, the patient will not need anymore treatments?

[agardner]

De Gardner, thanks again for your participation.

What do you think of Follica and wounding used as a method to create new follicles in conjugation with application of fgf9?

What do you think of replicel?

I think the wounding idea is very intersting, as if you think about the normal hair cycle the movement of the follicle through the tissue is reminiscent of a very minor wound. Some factor released during this wounding process may be important in follicle maintenance, such as FGF9. The next question, if this is shown to be key, is why is this signal lost.

For replicel, I really don't know anything more than you guys until some information is released. They face the same hurdles as the other groups if they're expanding cells in the lab, but they may have overcome those.

[agardner]

Dr. Gardner,

Many thanks for joining our forum.

1) Has there been any work done with eyebrow follicles similar to what you are doing with hair follicles? Would/could the same factors apply for culturing and eventual transplantation of eyebrow hair? Further, do you think these hairs could be transplanted onto the face of someone who lost their eyebrows due to severe burns, and may have scar tissue?



2) Has any of this research been applied to conditions such as Peyronie's Disease or Dupuytren's Contracture? (I hope there are teams working on these devastating conditions.) Might these fibrotic phenomenons be cousins to what happens in a balding scalp?


Thank you for your time.

Not specifically, but what we do know is that directly transplanted follicles tend to retain their initial character. Currently this character is lost when we expand them, and as we've not rescued full follicle formation we can't currently type the follicles formed. So it may be possible that follicles from anywhere on the body can be pushed into any hair type after culture, or that we need specific follicles for specific hair types.

Not that I'm aware of, I don't know much about either of those disorders. Some of the symptoms correlate with those of fibrotic balding disorders but the underlying causes could be very different.

[agardner]

Question:

You mentioned that lab grown follicles from DP cells may not function as desired due to the missing fatty tissue thats connected to follicles with typical hair transplants.

Could performing a fat transfer via fat grafting by implanting it from the abdomen prior to injection or implanting bare follicles be a potential solution to this possible problem? Is this fatty tissue basically the same as it is in scalp or are there differences?

Thank you!

This grafting, or adding fat stem cells to our 3D models are something that we think might improve inductivity. The latter is easier to achieve technically and in the clinic.

There are differences but we're hoping that the mix of various follicle cells in our models will point the fat cells towards a more follicle lineage.

[nameless]

Dr. Gardner, I'm confused because I read an abstract which said scientists at Nanfang Hospital of Southern Medical University in China have used a 3D Matrigel Culturing Method to culture cells and retained gene expression even in high pass culture - up to 8 passes. Here's the abstract called Controllable production of transplantable adult human high-passage dermal papilla spheroids using 3D Matrigel culture:

http://online.liebertpub.com/doi/abs....TEA.2013.0547

* I have not seen the entire article so I don't know all of the specifics, but doesn't this abstract indicate that this group of scientists have done 8-pass culture and still retained trichogenicity by using a 3d matrigel culture?

* I read a post by another poster in one of the threads here at the bald truth that seemed to indicate that these Chinese scientists were able to retain the same amount of trichogenicity at pass 8 that is in fresh cells. Is that correct?

* What do you know about the work being done by the scientists at Nanfang Hospital of Southern Medical University in China?

* Are your team, and all of the other teams, utilizing the technological knowlege and advances that the scientists at Nanfang Hospital of Southern Medical University have achieved?

[nameless]

This grafting, or adding fat stem cells to our 3D models are something that we think might improve inductivity. The latter is easier to achieve technically and in the clinic.

There are differences but we're hoping that the mix of various follicle cells in our models will point the fat cells towards a more follicle lineage.

Dr. Gardner now that we're talking so much about fat cells that makes me think that perhaps simple repeat injections of the correct growth factors and proteins might cure hair loss. The thing is that when there is abundant fat cells under the follicles and around the follicles that prompts environment prompts healthy hair growth by sending growth factors and proteins to the follicles. So it does seem to me that by simply injecting those same growth factors and proteins you could get the same result - healthy hair growth.


I know that histogen injected those same growth factors and did not achieve substantial regrowth of hair but do keep in mind that Histogen only used one treatment date but fat cells in the body are *continually* sending those growth factors and proteins to the follicles. that Histogen's treatment didn't produce a major breakthrough but that could be because Histogen only did one treatment date. There were no follow-up dates. In order for Histogen to mimic what the fat inside the body does Histogen would have to do repeat treatments so that there could be continuous growth factors and proteins getting to the follicles.

[nameless]

Dr. Gardner below is an article I found in a thread about DKK1's inhibitory effect on hair growth at this very website. As you know Histogen's growth factor phase 2 study results were not so great. I'm wondering if possibly the reason Histogen's treatment growth factor treatment didn't work so well is because all histogen does is add the growth factors necessary for hair growth but they didn't add a medicine that could remove the thing that is blocking hair from growing - DKK1.

That's the way it is with prostaglandins. In the prostaglandin model for hair growth you have to negate PGD2 because it inhibits hair growth, and you also have to increase PGE2 because it promotes hair growth. You have to do both. You have to fix both ends of the equation.

Couldn't the same thing be true with growth factors? If you want to regrow hair using the growth factors model for hair growth you may also have to add the growth factors that promote hair growth and negate the thing that inhibits hair growth - DKK1. You would be fixing both sides of the equation. What do you think?



http://hairdresserslivingston.blogsp...loss-2014.html

[Swooping]

Aaron Gardner, first of all thank you for your hard work, research, information and your transparency. Please take the time to read this, it will be a long story. But I think discussing these things and digging deeper into pathways is important. If everyone would contribute on the forums, we could crack AGA perhaps, or have a better understanding by connecting the dots and digging up information. There is tons of precious information available online. Unfortunately this happens rarely, most people like to be a sitting duck or think they can’t contribute. If only we would put all our brains together and discuss and evaluate possibilities and figure things out. Most don’t even exactly understand how complex and broad these pathways are. Don’t get me wrong on this but everyone can contribute especially nowadays with the information system getting bigger and bigger, everybody can play as a sort of “scientist”. It all just takes determination, will power and hunger. But we all face the same problem on these forums, don’t we? I lost hope in that though lol, but I don’t face the problem anymore that much as I luckily got almost all of my hair back.

In my opinion DKK1 antagonizing won’t work in growing hair on itself like some people contrary think. First of all it has been tried topically by members. Furthermore there are running clinical trials of DKK-1 antagonists/anti-bodies running DKN-01 and BHQ880. No hair growth as a side-effect was reported in them. I think there is even running 1 more. Remember I’m not talking about mice but humans here in every aspect of my story. Most research is done on these little buggers, but they have awesome regenerative capacities. (1, 2)

Same with PGD2 it was a nice discovery but again people were hyped up as hell because they thought well; “that must be the key in regrowing our hair”. Obviously such things are a very nice discovery but I know and I think you agree with me that there is a way bigger picture around it. And antagonizing such singular pathways won’t regrow our hair. If it would be the key these internal GPR44 blockers would already prove some hair regrowth in people taking them as a side effect. Secondly people have already tried using synthetically antagonizing this pathway topically and it did only a little, nothing spectacular at most. Still the importance is there of discovering such things, but nothing to get too hyped up and thinking that it is the cure. Who knew a few years ago that PGD2 was overexpressed in bald scalp though, and we are getting to know more everyday! Just now we discovered that transcient amplifying cells are most likely involved in the hair cycle! Now on why at least such a singular pathway won’t prove to be successful.

A example is minoxidil. I always was amazed what a monster minoxidil is in regrowing hair. I suppose that in people whose sulfotransferase is high and working people can really regrow tons of hair on it (3, 4, 5…). I have literally seen many legit pictures of guys going going from NW4-5 to literally almost NW1 with it. Albeit rare, such extreme regrowth does happen and often people gain 1 or 2 Norwood with it. So obviously amazed by the power of Minoxidil I started searching for the mechanism of action. When I started the journey as a complete (bald) noob I only thought of “increased bloodflow”. But nowadays I know what a beast it is and I am not even going to line up all the actions of minoxidil (obviously the knowledge of the exact mechanism is only getting better, and broader) we’ll get to the bigger picture in a moment. Minoxidil (6, 7, 8,) ;

- Increased phosphorylation ERK and AKT
- Increasing BCL-2/Bax Ratio (damn!)
- Decrease P53 (overexpressed in scalp) > also P21 (downstream) (wow!)
- Increase B-catenin in human DP (quite obvious though if above happens)
- Increase VEGF in human DP
- Increase PGE2

There are even some more potential targets for minoxidil. Dr. Angela Christiano had them written out in a paper like a half year ago I think, but doesn’t matter for now. Well as we see minoxidil isn’t only a beast because of “improved bloodflow”. Heck it targets multiple targets like a goddamn beast which sometimes can grow someone his hair back almost completely in combination with a anti-androgen or at least aid in regrowing. But that isn’t because it supposedly targets only 1 pathway! It’s also hilarious that to date we don’t have a better growth agent than minoxidil. 30 years later minoxidil still reigns king and even Histogen or any other company can’t manage to get those results atm . Well no wonder I guess given the above. By accident this molecule has been proven to be damn good at growing hair.

Now about DKK1… Why the heck would antagonizing DKK1 grow hair when there are tons of factors included in the pathways. P53, when it is overexpressed in scalp (9..) and upstream of DKK-1 have fun antagonizing DKK1. A simple search for P53 + wnt and we see that P53 completely destroys the WNT pathway (by also upregulating DKK1). This is just a simple single example.

Let’s look at a picture done by a neurosurgeon and 2 random guys who are both in a completely other field but were determined and curious to figure these pathways out and play around with them. So all credit to them;



This even isn’t everything off course and is expanding every day. Heck we could even update it today and make it bigger! It is pretty complex isn’t it? That’s why only antagonizing DKK1 or PGD2 won’t work. Just look at minoxidil how a multiple of a action beast that is (probably indirectly already antagonizes DKK-1 lol). Look what Histogen is doing. They culture dermal fibroblasts under hypoxic conditions and deliver growth factors to the scalp of the FGF, WNT, SHH (even more) family and even that doesn’t completely grow someone his hair back. It does grow some hair but not better than minoxidil and it is far from the cure. Sometimes even combining all possible treatments nowadays doesn’t get you to grow hair. Even PSI, a proteasome inhibitor which acts at multiple levels grew some hair in clinical trials but supposedly wasn’t as beastly as minoxidil and did not hit the market.

However!!!!! Sometimes ALL these treatments combined don’t even grow hair at all in some advanced cases. NONE! Why is that????!!!! Damn we are hitting MULTIPLE and MANY beneficial pathways for our hair follicles and they still stay miniaturized, even when you block the Androgen receptor with it?!

Well simply because extensive DNA damage has been done, the cells lose their proliferation and are beyond of their capacity to regenerate..

Thanks for reading this if you have come this far. Bet most won’t, probably bored as hell . Again if we could only all put our head together to get more knowledge with the available information. Just look at what 3 people can do in a short matter of time by researching and discussing (diagram here above). I could go way more in depth about everything but that is not needed. My questions for you Aaron;

- Do you agree somewhat with me that alternating singular pathways like PGD2 or DKK-1 obviously ain’t going to do much in the grand scheme of things? What is your view on it?

- I wonder myself, if creating apoptis in our damaged cells (which lack profileration and can’t regenerate themselves even with treatments like minox, and blocking AR etc.) would fix the problem? Is such a thing even possible?



1. http://clinicaltrials.gov/ct2/show/N...=dekkun&rank=1
2. https://myeloma.org/pdfs/ASH2009_Padmanabhan_750.pdf
3. http://www.ncbi.nlm.nih.gov/pubmed/24773771
4. http://www.ncbi.nlm.nih.gov/pubmed/24283387
5. http://www.ncbi.nlm.nih.gov/pubmed/1349030
6. http://www.ncbi.nlm.nih.gov/pmc/arti...kms-22-283.pdf
7. http://www.ncbi.nlm.nih.gov/pubmed/21524889
8. http://www.ncbi.nlm.nih.gov/pubmed/9580790
9. http://www.ncbi.nlm.nih.gov/pubmed/18702626

P.S. won't be bugging and boring you anymore after this lol, don't worry . Keep doing what you do it is awesome! Some day we'll have this cracked whatever way it will be.