Q&A with Dr. Aaron Gardner

[agardner]

So I'll summarise our workings on the DS:

• Freshly isolated DS is as competent as the DP.
• The DS acts as a reservoir for DP cells during the morphological changes of the hair cycle, see:
  http://www.akclinics.com/images/regrowth-cycle.jpg
• In our hands 2D expanded DS do not retain inductivity.
• In our hands 3D culture of DS does not restore inductivity.
• We are attempting to restore inductivity in the DS by increasing expression of DP specific genes in the DS, but have currently not had any success.
• This is designed to help us identify key genes so that we can hopefully in the future use dermal fibroblasts, a much easier to isolated and expand population than DS or DP. See the Rendl labs work, they are attempting to go direct from DF already, very exciting work.

As for Replicel I honestly don't know as I've not seen any data. I know they reported the findings of their clinical trial in Japan but I've not seen the data myself. I would imagine they have the same issues as other and other groups, but, they may be doing something different that has allowed them to get past this. Again, it will be very interesting to see the findings and I think it's a very valid approach as a whole but I don't know the specifics.

[agardner]

Couldn't we just dye the new hair?

I think that if you guys can just figure out how to get us the hair we will just dye it to get color.

Yes, of course. That's why groups are focusing on getting reproducible induction first, other steps like colouration, angle, patterning and surgical delivery will come after that.

[agardner]

Mr. Gardner I have a few important ques. #1 Will hair cloning work for someone with a Norwood 6 or 7? And if so, will it restore a full head of head, with a normal hairline as well. #2 If all that worked out, once you are finished with the procedure, you won't have to go back ever again? #3 In the future when you develop gray hair will the cloned hair turn gray as well? #4 Last but not least how much do you think this would cost for a person with a Norwood 6 or 7, BALLPARK/EDUCATED GUESS?? Thank you, Mr. Gardner for you time.

If we make an inductive construct it should work in any instance. But, as I've mentioned previously a balding/bald scalp as underlying issues that mean follicle maintenance will likely be poor. So, co-therapies to prime scalp for treatment and help maintain follicle survival will be required.

It will be interesting to see if restoration of follicles to balding/bald scalp improves the quality of the scalp though.

As for cost I honestly have no idea, an educated guess would be something similar to the current top end hair transplantation clinics. That's a question for when one of the groups gets closer to testing.

[agardner]

Are there specific genes that you think may be crucial for inductivity (already known, or in theory)? I imagine they could be knocked down (using something like RNAi) in non-proliferated DP cells to examine their relative importance?

Yes there are several genes that are known to be important, LEF1, beta-catenin, various other members of the Wnt signalling pathway. Dr Higgins in her paper identified several thousand genes that demonstrate changed expression (but only a small number of these will actually be relevant for the purposes of inductivity).

Knock down of gene expression in a freshly isolated DP is not really possible, the cells are quite difficult to manipulate genetically in ideal scenarios (2D culture, rapidly proliferating), when they are bunched up as a DP or a DP sphere I don't think it would be possible. However, several groups including ourselves are trying it the other way around, attempting to restore these genes to DP and other non-DP cells. See the Lendl group for the most ambitious attempts.

[agardner]

Even if the DP cells are derived and multiplied from an apparently 'resistant' area of the scalp, i.e. the back of the head?

If those follicles exist then yes they will likely fare better. However balding/bald scalp is less "healthy" (in relation to follicle support), so constructs will be being transplanted into a less healthy environment, the constructs themselves may be very viable but without proper support and interaction I would hypothesize that they wouldn't retain resistance. Hence why I think that co-therapies to prime the scalp prior to transplantation and maintain a healthy environment after will be vital. Until we can somehow address any underlying causes.

[agardner]

Bummer, 6-8 weeks to deliver a treatment is almost certainly going to be expensive. Thanks for the clarity!

Perhaps not, in the hair transplant clinics that I've visited there are large numbers of staff working together to prepare follicles for re-grafting. Isolation and expansion "could" be carried out by a much smaller team, the surgeons time would likely be the same for both.

[hgs1989]

Q:
a bit off topic:
Some growth factors are know to be expressed in the hair follicle during Anagen phase mainly afgf, bfgf, kgf, igf-1. when injecting such proteins into the scalp, do you think they will bind to cells and promote anagen and delay catagen thus elongating miniaturized hairs and thicken the entire scalp hair?

[sdsurfin]

yes, it's interesting that aderans even had some positive results at all. however, it makes sense now that their method lead to nowhere.

even funnier (but also dangerous for patients) is that nigam is still tinkering around with his planless dp cell injections.
someone should tell him to switch to DSC cells so that he can replicate the Replicel method.
he shouldn't add any further experimental compounds and dangerous crap. just expand DSC cells en mass in 2D only and then inject them back. this will probably give some results, depending on how many treatments and doses. replicel phase 1 showed already that it's safe, so it would be a good starting point for nigam. he should forget about all other crappy methods and protocols he's using currently so that no patients are in danger anymore. try DSC cells instead.

Please stop going off topic. Also no one said that dsc cells alone are any good for inducing new follicles. That is why all these teams are using DP cells and optimizing them. Lets not overwhelm dr Gardner with nonsense about nigam or other teams or treatments that are not as advanced. They will be whatever they are and talking about them won't make them come faster. Let's keep this thread for Q and A about what's being studied. Thanks

[sdsurfin]

Can we keep this to question and answer please? There is no cure and no cure planned for trials, so please stop discussing the cost and specifics of a cure. Of course dr Gardner does not have those answers. For once we have someone reputable and intelligent answering questions, for the love of all that's holy let's keep this thread free of speculation about things like replicel etc and unrelated jibber jabber.

Dr. Gardner: When I mentioned DSC cells I only meant to say that they seem to have their own unique interactions with the DP and epithelial cells. Their shape and interactive potential would seem to play a role in helping the DP and epithelial cells align themselves correctly. For one, you mentioned that your team has had trouble with the stickyness of the epithelial cells that you are adding to the mix. Maybe the sheath cup cells might provide both chemical signals and the basic shape of their design in a way that facilitates this stickiness. I'm not sure if you've already tried this or if other teams have tried it, but to me it seems illogical to expect the best inductivity without using the combination iof cells that the body naturally arranges. I'm happy that you'll be working with fat cells, they seem crucial to making and maintaining viable hair.

A random question: has anyone studied the hair cells in moles/freckles? I have a freckle on my arm that keeps growing new darker hairs than the area around it. They aren't just blacker due to the pigmentation, but are also longer and thicker, and I get more over the years. Might these hairs hold clues as to what makes cells more or less apt to produce hairs?

[nameless]

yes, it's interesting that aderans even had some positive results at all. however, it makes sense now that their method lead to nowhere.

even funnier (but also dangerous for patients) is that nigam is still tinkering around with his planless dp cell injections.
someone should tell him to switch to DSC cells so that he can replicate the Replicel method.
he shouldn't add any further experimental compounds and dangerous crap. just expand DSC cells en mass in 2D only and then inject them back. this will probably give some results, depending on how many treatments and doses. replicel phase 1 showed already that it's safe, so it would be a good starting point for nigam. he should forget about all other crappy methods and protocols he's using currently so that no patients are in danger anymore. try DSC cells instead.

Aren't the researchers adding various agents to their cell theories? I'm sure some of the researchers are trying wnts and the like, aren't they?

[joachim]

but hey, another thought now, althouth i'm sorry it's little bit offtopic with nigam again:
wasn't his donor doubling theory like cutting the follicle exactly at a certain point to separate the whole dermal papilla and the whole dermal sheath cup (like in the replicel video shown)?

because we know now that both DP and DSC can induce a new follicle. and if he cuts the follicle precisely so that the DP and DSC stay undamaged, his theory makes absolutely sense now. however, he's doing something wrong, if he doesn't get results at all. but his theory is not BS in my opinion. i'm curious if mwamba will find out some details which he can optimise so that efficacy will be increased. if he takes the time to get insight into the whole process maybe he can achieve some access on it. even 20% or 30% donor regeneration would be great. pilofocus is definitely not going to give more than 20%, if regeneration at all.

[joachim]

yes, it's interesting that aderans even had some positive results at all. however, it makes sense now that their method lead to nowhere.

even funnier (but also dangerous for patients) is that nigam is still tinkering around with his planless dp cell injections.
someone should tell him to switch to DSC cells so that he can replicate the Replicel method.
he shouldn't add any further experimental compounds and dangerous crap. just expand DSC cells en mass in 2D only and then inject them back. this will probably give some results, depending on how many treatments and doses. replicel phase 1 showed already that it's safe, so it would be a good starting point for nigam. he should forget about all other crappy methods and protocols he's using currently so that no patients are in danger anymore. try DSC cells instead.

[hellouser]

i just noticed something: working with DSC cells by just injecting them could truely be effective because: compared to the dermal papilla which is surrounded by all other cells the dermal sheath cup is accessible from outside. thus, it's relatively easy for the injected DSC cells to attach to the existing dermal sheath cup. but if you inject DP cells they are not able to find their way to existing dermal papilla because they can't go through the other cell walls like DSC and outer root sheath. this is probably the reason why nigam's and other experiments failed when they tried to rejuvenate the follicles with the use of 2D cultured dp cells.
does that makes sense? your opinions, please.

That sounds pretty reasonable! However, Aderans did show some success with DP cells, not a whole lot but there was greater density in their results.

[nameless]

At the moment they would come out un-pigmented. Incorporation of patient melanocytes (the cells that provide the colouration) is something that is in the works.

Couldn't we just dye the new hair?

I think that if you guys can just figure out how to get us the hair we will just dye it to get color.

[joachim]

i just noticed something: working with DSC cells by just injecting them could truely be effective because: compared to the dermal papilla which is surrounded by all other cells the dermal sheath cup is accessible from outside. thus, it's relatively easy for the injected DSC cells to attach to the existing dermal sheath cup. but if you inject DP cells they are not able to find their way to existing dermal papilla because they can't go through the other cell walls like DSC and outer root sheath. this is probably the reason why nigam's and other experiments failed when they tried to rejuvenate the follicles with the use of 2D cultured dp cells.
does that makes sense? your opinions, please.

seems like DSC is the new key to success.
Replicel in combo with Histogen could be awesome!
replicel phase 2 results are important now.