Q&A with Dr. Aaron Gardner

[sdsurfin]

thanks

Thanks Dr. Gardner for your time and patience.

It seems to me that all the research teams are tackling hair growth one step at a time, as would be expected. I'm glad that you've cleared up the fact that no one has achieved full inductivity retention, or full gene expression (many on here didn't seem to understand the difference).

Two ideas as far as restoring characteristics is concerned
a) would it be of any use to not only combine cells, but also add growth factors such as fg9, or whatever compounds are implicated in the wnt pathway, which seems so crucial to follicle growth?
b) shape-wise, and from a designer's perspective, the sheath cup cells seem to be the most crucial as far as keeping everything in line, would it not make sense to start incorporating these into your mix right away? Maybe your epithelial cells are not "sticky" enough because they are only a second part of the puzzle, and you need all the pieces. Just a thought.

Another thing that I'm curious about is if any of you research teams have any solid ideas of why baldness actually happens in a broader sense. I know it is activated by androgens, but is it a matter of every cell in the scalp being programmed and implicated in these changes, or is it just the DP cells that have the receptors, and are sending signals to the environment- or is it the fat cells controlling the game? It seems a big effort has been made to understand the interaction between fat cells and DP cells, and I'm wondering if the key to retaining inductivity and maintaining hair growth doesn't lie in the interaction with the fat in the skin.

The epithelial, DP, and other hair follicle cells seem to be able to work together to create a follicle, but the fact that these follicles are small in vitro, and not the same as healthy hairs begs the question of what it is that they are missing. I doubt full gene expression is the complete answer, and my guess would be that they need to interact with not only epithelial cells, but also whatever other cells are in the scalp. are fat cells the answer? If so, can you guys begin to culture DP spheroids in a way where they are exposed to healthy fat cells?

I think you're right about it being hard to induce and maintain hair in a balding scalp, and thus I don't think any of the research will go anywhere as far as curing alopecia until the roots of the condition are understood (are they?) . A workaround solution could be the creation of follicles in engineered skin, and then the implantation of these follicles with new surrounding tissue, similar to current transplants.

[downandout]

sdsurfin, I think fat cells can play a huge part in this. I am definitely not an expert, but check out the below link. It was posted by another user here and the results are pretty amazing. They used an adipose derived stem cell protein.

http://www.baldtruthtalk.com/showthread.php?t=16196

[Artha]

Are these guys working on an actual cure or treatment, or they only doing research on hair follicle and skin?

[StinkySmurf]

Will the new hair color match the old hair?

Thanks for answering questions Dr. Gardner!

Will the color of these new hairs match the existing hairs?

If you have a head of gray hair will the new hair come out gray?

Thanks again!

[Arashi]

I'm glad that you've cleared up the fact that no one has achieved full inductivity retention

That's indeed what I understood too from Dr Gardner's words, but weird thing is that Desmond claims that all the teams achieved that already !?!?! Did he misunderstand their words !?!

or full gene expression (many on here didn't seem to understand the difference).

As I understood NOBODY knows that exact difference. Gardner's/Jahoda's group showed that the 3d cultured DP cells were only 40% similar in genes with their original counterparts, this was enough to induce hairs but not enough to induce hairs with cosmetical viable characteristics. I think it's currently unknown how many genes and which genes exactly need to match to achieve that.

[nameless]

1) We rapidly expand our DP cells in 2D culture, during this step they lose their inductive capacity. After expanding the cells we transition to a 3D model. Just by placing the DP cells in a 3D system they form tightly packed spheres. Dr Higgins in her paper showed that this act of forming a sphere restores ~40% of the genetic signature of a functional human DP that is lost during 2D expansion. We're attempting to coat with epithelial cells, when they work we see markers of inductivity turned on that aren't present even in the dermal only spheres. We haven't repeated Dr Higgins work looking at the genetic signature, but we are going to, so I can't give a numerical figure for restoration. It will be higher than ~40% restoration, but I would think it unlikely to be 100%.

2) We use the same culture and coating techniques however sometimes it works and sometimes it doesn't. We've looked to see if there are any correlations e.g. donor age, donor tissue location, cell passage number etc. but nothing has stood out so far. So there is patient variability, we need to understand what is causing this variability. We are attempting several things:

• Differnt epithelial cell populations, e.g. hair specific populations
• Different 2D epithelial expansion techniques
• Different coating techniques
• and several other things

Thanks for responding Dr. Gardner.

Another issue is that some posters raise the issue of hair direction and angle. This is why I think that it's better to implant cells rather than implanting entire follicles. I think that if you implant the cells the cells will incorporate the follicles that already exist and the cells will pass through those existing follicles so the hair that grows will be the same as it was before the hair miniaturized down to peach fuzz. On the other hand if you implant whole follicles then you will have to count on the artistry of the implant specialist who implants the follicle and it's very hard for any person to implant 10s of thousands of whole follicles without ever making a mistake in each person. This is why even the best of the best hair transplant specialists have some unsatisfying results. I also think that when Dr. Jahoda first tried implanting cells from his wife into his own arm those cells caused hair to grow on his arm so I think that this proves that there is no reason to create whole follicles since implanting the cells can cause hair to grow.

What's wrong with the idea of finding out how to get mass-pass cell culture inductivity up higher and higher until you get it at or near 100% and then injecting those cells?

Also, you mentioned that the hairs might not last long because the hair will still be vulnerable to androgens. I wanted to say a few things about that:

1. As we age we produce less androgen so that will allow the new hairs to last longer than when we were kids.

2. Androgens start damaging hair in our earliest teens and it takes years for hair loss to cause significant cosmetic damage so even if the lower amount of androgens (since we produce less androgen as we age) caused us to lose hair at the same rate as when we were kids all that means is that we would have to go in for re-treatments possibly every 5 - 10 years. I'd rather do that than be bald.

3. You also indicated that the reduced fat could allow the androgens to miniaturize hairs faster and so I'm wondering why you can't simply inject fat cells to solve that problem? Some people are already trying to inject fat cells as a treatment for hair loss. They are using fat cells from the stomach. I think that perhaps it might be better to use fat cells from under the follicles that are producing strong healthy hairs in the donor region because those fat cells are signalling the follicles to produce strong healthy hairs whereas the stomach fat cells are signaling the follicles to produce short fine hairs that are on our stomachs. Anyway, when a follicle is pulled to gather DP cells/epithelial cells for mass-pass culture you could also pull the fat cells underneath and mass-pass culture them for implantation into the recipient area and back into the donor area as well.

[joachim]

dr. gardner,
you said the hair follicle including hair shaft in vitro of lauster's biochip reactor was tiny.
in 2009 they presented the tiny so-called microfollicle already. if it's still the case today, what happened during all these years? are you sure they didn't scale it up already?
we will hopefully see the presentation soon when desmond puts it online on the weekend.
will the presentation answer some questions and really represent the latest status, or did they present some old news to not reveal all their latest findings?

also, i was wondering, if you and jahoda would get a license maybe to use their biochip technology for your own research. i saw you stated that there is of course some sort of competition to keep the job and so on, but is there no chance to get in touch with team lauster and exchange some findings? they could profit of your and jahodas big knowledge about DP cells and culturing stuff, and in return you could proceed with your culturing experiments with an optimum environment from the biochip. i would see it more as a win-win situation than a hard competition between those two teams. because if the biochip is the only possibility to allow for optimum culturing, other teams would only get access to it through licensing because of the patents they hold.

but that's just an idea. i just can't see a way how the manual culturing in dishes with all these hanging drops techniques etc. can pan out to achieve fast access. if i understand it correctly, it's time consuming and has failure rates due to the fact that the dishes have to be monitored and supplied manually every few days.

i would love to see at least european labs working together like you/jahoda and TU berlin to bring this thing to the next level. there's also no risk for both teams to lose their job here =) because both teams are having invaluable know how.

[nameless]

Thanks Dr. Gardner for your time and patience.

It seems to me that all the research teams are tackling hair growth one step at a time, as would be expected. I'm glad that you've cleared up the fact that no one has achieved full inductivity retention, or full gene expression (many on here didn't seem to understand the difference).

Two ideas as far as restoring characteristics is concerned
a) would it be of any use to not only combine cells, but also add growth factors such as fg9, or whatever compounds are implicated in the wnt pathway, which seems so crucial to follicle growth?
b) shape-wise, and from a designer's perspective, the sheath cup cells seem to be the most crucial as far as keeping everything in line, would it not make sense to start incorporating these into your mix right away? Maybe your epithelial cells are not "sticky" enough because they are only a second part of the puzzle, and you need all the pieces. Just a thought.

Another thing that I'm curious about is if any of you research teams have any solid ideas of why baldness actually happens in a broader sense. I know it is activated by androgens, but is it a matter of every cell in the scalp being programmed and implicated in these changes, or is it just the DP cells that have the receptors, and are sending signals to the environment- or is it the fat cells controlling the game? It seems a big effort has been made to understand the interaction between fat cells and DP cells, and I'm wondering if the key to retaining inductivity and maintaining hair growth doesn't lie in the interaction with the fat in the skin.

The epithelial, DP, and other hair follicle cells seem to be able to work together to create a follicle, but the fact that these follicles are small in vitro, and not the same as healthy hairs begs the question of what it is that they are missing. I doubt full gene expression is the complete answer, and my guess would be that they need to interact with not only epithelial cells, but also whatever other cells are in the scalp. are fat cells the answer? If so, can you guys begin to culture DP spheroids in a way where they are exposed to healthy fat cells?

I think you're right about it being hard to induce and maintain hair in a balding scalp, and thus I don't think any of the research will go anywhere as far as curing alopecia until the roots of the condition are understood (are they?) . A workaround solution could be the creation of follicles in engineered skin, and then the implantation of these follicles with new surrounding tissue, similar to current transplants.

sdsurfin please explain the difference between inductivity retention and gene expression. I'm under the impression that they are essentially the same. I'm thinking that cellular hair "inductivity" refers to genetic instructions in the cell for those cells to morph into hair and "genetic expression" is merely the expression of those genes. These look to me like very similar concepts. It seems to me that the measurement of one would EQUAL the measurement of the other. In other words, if they have achieved 40% genetic expression then that also means they have achieved 40% hair inductivity. And if this is correct then that is an improvement over Dr. Jahoda's numbers late last year because back then he achieved 22% I think. So it looks to me like it's nearly doubled.

Can someone please explain to me why I'm right or wrong?

[joachim]

from what we have read, Dr. Xu is going the other way over iPS cells to multiply the iPS cells in mass and then convert them rapidly into DP cells which should create full inductivity and full gene expression of the cells. what is your opinion about that way? is it 100% sure that if someone finds a solution for converting iPS cells to DP cells that these DP cells will really have the full inductivity and full gene expression? if not, dr. Xu is wasting his time here, and we all should warn him =D

[Arashi]

from what we have read, Dr. Xu is going the other way over iPS cells to multiply the iPS cells in mass and then convert them rapidly into DP cells which should create full inductivity and full gene expression of the cells. what is your opinion about that way? is it 100% sure that if someone finds a solution for converting iPS cells to DP cells that these DP cells will really have the full inductivity and full gene expression? if not, dr. Xu is wasting his time here, and we all should warn him =D

iPS is a very new approach, only recently the first clinical trial ever with iPS cells has started recruiting (read more: http://www.ipscell.com/2014/01/stem-...-studies-more/ ). However its outcome is of course as uncertain as the DP culturing approach. But I think it's a good thing to have different teams try different approaches, it increases the likelihood of success.

[joachim]

about jahoda's experiment:

please everyone correct me if i'm wrong here:
we heard that jahoda combined epithelial and DP cells and implanted them into his arm (or was it his wife's arm?). and the cells developed into a normal hair then. i think arashi has some good info on that. arashi, maybe you can elaborate on that a bit. since we heard that story, we we're assuming that epithelial cells and dp cells are the only cells which are required for forming a hair follicle.
the important fact here: jahoda used fresh isolated cells which didn't go through multiplication (because they would lose their properties). so this was a proof of concept that those 2 cell types lead to the formation of a new follicle, IF the cells didn't lose their properties.

is that story right so far?
if so, is this experiment reproducable anytime? or what details are we missing here?
because if this were true the only puzzle to solve would indeed be to crack the code how to expand/multiply DP cells without losing their properties. and THIS is what we all thought was figured out by some teams all around the world and also presented on the hair congress.

and also important here: is THAT hair still growing on the mentioned arm? we would like to see that =)

[Arashi]

about jahoda's experiment:

please everyone correct me if i'm wrong here:
we heard that jahoda combined epithelial and DP cells and implanted them into his arm (or was it his wife's arm?). and the cells developed into a normal hair then. i think arashi has some good info on that. arashi, maybe you can elaborate on that a bit. since we heard that story, we we're assuming that epithelial cells and dp cells are the only cells which are required for forming a hair follicle.
the important fact here: jahoda used fresh isolated cells which didn't go through multiplication (because they would lose their properties). so this was a proof of concept that those 2 cell types lead to the formation of a new follicle, IF the cells didn't lose their properties.

is that story right so far?
if so, is this experiment reproducable anytime? or what details are we missing here?
because if this were true the only puzzle to solve would indeed be to crack the code how to expand/multiply DP cells without losing their properties. and THIS is what we all thought was figured out by some teams all around the world and also presented on the hair congress.

and also important here: is THAT hair still growing on the mentioned arm? we would like to see that =)

Jahoda implanted some of his own Dermal sheath cells (those are cells surrounding the papilla) into his wife's arm and hair grew (with his characteristics, his hair color etc). This showed that Dermal cells can induce hair follicle formation. As I understood it he didnt transplant epethelial cells (like Tsuji lab did), but he placed the dermal cells next to epethelial cells.

if this were true the only puzzle to solve would indeed be to crack the code how to expand/multiply DP cells without losing their properties

That's also my understanding.

[joachim]

i forgot to mention in the previous post:

according to an article from 2013 team lauster said they will be starting human trials in 2014. is this still the actual plan? if so, how would that be possible? if the biochip reactor still produces tiny hair only, there's no reason to implant it.
or maybe the theory behind it is that the implanted microfollicle will grow to a normal and strong follicle after some month, or maybe it even takes a year. is there a possibility for such a scenario?

[joachim]

Jahoda implanted some of his own Dermal sheath cells (those are cells surrounding the papilla) into his wife's arm and hair grew (with his characteristics, his hair color etc). This showed that Dermal cells can induce hair follicle formation. As I understood it he didnt transplant epethelial cells (like Tsuji lab did), but he placed the dermal cells next to epethelial cells.


That's also my understanding.

what? jahoda's DSC cells only? and in his wife's arm? what about rejection? why did jahoda do that? why not in his own arm?

and if DSC cells could do that trick alone, why not concentrate on multiplying those cells and inject them instead?

man, i'm totally confused now. i'm lost. it feels like the cure is here already but nobody is willing to go the final step =D

[hellouser]

Jahoda implanted some of his own Dermal sheath cells (those are cells surrounding the papilla) into his wife's arm and hair grew (with his characteristics, his hair color etc). This showed that Dermal cells can induce hair follicle formation. As I understood it he didnt transplant epethelial cells (like Tsuji lab did), but he placed the dermal cells next to epethelial cells.


That's also my understanding.

If that's the case, then Replicel's approach should work just fine. Did it take many months before the follicle formed and hair grew as normal from Dr. Jahoda's experiment?