Q&A with Dr. Aaron Gardner

[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?

[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?

[sdsurfin]

interesting

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

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

[Armandein]

Dr. Gardner:

I just read this article, and would love to hear your thoughts.

http://www.iflscience.com/health-and-medicine/scientists-use-lasers-regrow-teeth-stem-cells

Is it possible that using lasers on your DP cell constructs might help restore inductivity? Either while in vitro or in vivo? after reading that article, (and also considering the evidence that laser therapy does, to some small degree, aid in slowing hairloss), I think it just might be a very interesting thing to try. Maybe you guys can create multi-cell type constructs and then charge them up with lasers before implanting? It seems easy enough to do and might be worth a shot. Maybe what's missing when cells de-differentiate is not just instructions from other cells, but rather some kind of charge or energy that is maintained while inside the body. After trying different spatial, chemical, and polarity combinations, this seems a logical route to examine, no?

then, it is possible thar lasers can be useful with hairloss,..., the study say:
"We show that non-ionizing, low-power laser (LPL) treatment can instead be used as a minimally invasive tool to activate an endogenous latent growth factor complex, transforming growth factor–β1 (TGF-β1), that subsequently differentiates host stem cells to promote tissue regeneration"

[sdsurfin]

Dr. Gardner:

I just read this article, and would love to hear your thoughts.

http://www.iflscience.com/health-and-medicine/scientists-use-lasers-regrow-teeth-stem-cells

Is it possible that using lasers on your DP cell constructs might help restore inductivity? Either while in vitro or in vivo? after reading that article, (and also considering the evidence that laser therapy does, to some small degree, aid in slowing hairloss), I think it just might be a very interesting thing to try. Maybe you guys can create multi-cell type constructs and then charge them up with lasers before implanting? It seems easy enough to do and might be worth a shot. Maybe what's missing when cells de-differentiate is not just instructions from other cells, but rather some kind of charge or energy that is maintained while inside the body. After trying different spatial, chemical, and polarity combinations, this seems a logical route to examine, no?

[hellouser]

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!

[TheSwingingGate]

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?

Previously I worked on epithelial-mesenchymal interactions in lung fibrosis, a lot of the techniques are applicable across the various fields and something described in one organ can often be applied elsewhere.

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.

[Thinning87]

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?

[agardner]

Dr.Gardner,

This is kind of a personal question. Why did you decide to study hair? Did you just happen to fall into this field and went with it? What is your motivation. If you could research anything else, what would it be?

If I didn't have hair loss myself, I would think that hair is the most boring body part to research (no offense).

Actually my main area of interest is wound healing and regeneration, so I just happen to be working on hair at the moment and for the foreseeable future. Previously I worked on epithelial-mesenchymal interactions in lung fibrosis, a lot of the techniques are applicable across the various fields and something described in one organ can often be applied elsewhere. I.e the dermal-epidermal interactions in my 3D models.

Also the hair follicle is actually of great interest for lots of people as it has several features unique in the adult. Constant regeneration, some control of cycling, pattering, population interactions. It is also accessible for tissue biopsies, as opposed to say the lung or liver.

[agardner]

Interesting thoughts Dr. Gardner.

Of course, the approach you and your team are looking at is the holy grail of treatments, where you can culture cells and create practically limitless amounts of hair. But a treatment like that still seems a fair bit away.

In the meantime, you have many people who have decided to undergo hair transplant procedures, which are very time-consuming and labourious. With a follicular unit extraction (FUE) procedure, for example, thousands of follicular units can be extracted and implanted over a couple of days.

So if it really is as simple as splitting the follicle at the right point(s), why wouldn't hair transplant surgeons be able to incorporate it in their work? Instead of simply redistributing your hair with a hair transplant, you could potentially increase the number of hairs on your head and preserve the donor area by incorporating these doubling techniques.

A few surgeons/clinics have advertised this type of procedure but I have yet to see any convincing evidence of any hair multiplication, which leads me to believe that it's much more difficult to implement then it sounds. Overall, I think it has the potential to be a promising treatment to bridge the gap before a full-out cure is offered, so I'm a little surprised there hasn't been more research into it. But if progress with cell multiplication is going as fast as has been hinted, maybe it won't be needed

Because in order to split the follicle correctly it needs to be micro-dissected out of its surrounding tissues which accompany the follicle even during an FUE. This takes time ~3-5 minutes depending on the skill of the person and how "clean" the follicle was when it came out. So if you scale this up by the several thousand follicles required you end up with a very large number of man hours.

Lets take a perfect scenario where every follicle comes out clean and 3,000 follicles are used.

2 x 3,000 = 6,000 minutes or 100 hours. Paying for those 100 hours of labour is where the cost comes in as it's quite a technically demanding job and several people would be required = large wage bill. That's the only issue I can see with it, having enough capable staff and paying them enough throughout the procedure as obviously it's very unlikely that this perfect example would occur in the clinic.

[artika]

Will one require perfectly healthy follicles for this
method, so will this give a person with Dupa a full head of hair ( i understand that he will most likely need cotherapies to maintain it) but is cloning even possible when one has no follicles intact?

[sdsurfin]

Dr. Gardner:

We've talked extensively about the need for co-current therapies in order for the hypothetical follicles that might be induced by one of the teams to survive.

my question is- Do you believe that therapies will be on the same page as you guys when the inductivity probelm is solved? To my knowledge, there hasn't really been any advance whatsoever in the treatment or knowledge of AGA as a whole over the better part of a half century, except for a few vague hunches/products that have not shown particularly promising results, and are struggling to get funding, and really shabby existing treatments (if side effects and modes of action are considered. blocking one of the body's important systemic enzymes is like using an axe where scissors are required). Are you aware of any teams that could roll out effective therapies along a similar timeline to the studies on follicle inductivity?

My guess (and from the sounds of your answers) is that inductive germs or whole follicles will be produced sometime within the next decade, if not sooner. But what good does it do anybody if there's nothing out there to treat and help reverse the underlying condition? There is a lot of chatter on these forums about things like this chemical CB-03-01 and whatnot, but in my mind they all seem like completely untested and long-shot possible therapies with equally probable side effects. Do you have colleagues that are working to find something better? Or has the whole field of hair science veered towards stem cell research? I looked through the titles of the hair congress presentations and all I could find were transplantation talks, stem cell talks, and the odd talk by someone like cotsarellis rehashing information that hasn't really produced any results.

I guess what I'm asking is- is this going to just become another non-option for those of us who refuse to take finasteride because it is crippling to our minds and bodies? As someone much more entrenched in the study of hair loss, I'm wondering if you have any knowledge that might give us hope that some sort of superior therapy is in the works as well as your incredible work with stem cells.

[sdsurfin]

Ok great, thank you! I wish you guys luck!

[locke999]

Dr.Gardner,

This is kind of a personal question. Why did you decide to study hair? Did you just happen to fall into this field and went with it? What is your motivation. If you could research anything else, what would it be?

If I didn't have hair loss myself, I would think that hair is the most boring body part to research (no offense).

[agardner]

Just watched your presentation Dr. gardner, very interesting. The fact that you can test for the different gene expressions is amazing.

I still can't help but think that the roadblock to having these different cell populations stick togther and then communicate is more a question of spatial design more than the types of cells being used. In a human, the epithelial cells, bulge cells, DP cells, and sheath cup cells are placed very specifically in relation to each other in a more solid medium, as well as in relation to gravity, and and even in a hanging drop, i would imagine the cells feel quite lost in space.

every time I look at a drawing of a hair follicle, I wonder why the sheath cup cells are not being used to guide all the other cells. Would it not make sense to build a sheath cup construct within a hanging drop or in some sort of tiny fluid or gel filled compartment, and then add DP cells and epithelial cells? I would imagine that the very specific cup shape that the DSC cells create (and likewise the bulge area on top) in a follicle might be a trigger for epithelial and DP cells to aggregate the way that they do naturally in vivo. What about culturing these cell types in very narrow cylinder shapes, where they would be stacked on top of each other? It's interesting that in your presentation, inductive DP spheres pull down epithelial cells. Maybe DP cells need to be on top of DS cells in relation to gravity, and bulge cells/epithelial cells need to be on top of DP cells in order for them to act "sticky." I realize I'm kinda shooting in the dark, but if the biggest hurdle so far was one of design (learning to culture in 3D drops), then I wonder if the rest of the puzzle doesn't lie in spatial thinking as well. In this respect, 3D printing of the different cell types into a lifelike arrangement does seem like an exciting avenue to pursue.

another different idea: Is it possible that the instructions for inductivity and aggregation lie in stem cells/factors that are present in an embryo but not in an adult or in a lab setting? might there be a cell type that is specially tasked to induce follicle formation, and which has been overlooked due to a lack of examination and comparison with embyonic tissue? just a thought...

The usage of a more solid medium is something that other groups are attempting, in our hands we found it very difficult to keep the constructs intact for any length of time.

Polarity is something that we are definitely interested in inducing in our models but we have a few other things to try in the hanging drop co-cultures before we give up on them yet. The presentation by Beren Atac was very interesting to me, they are able to coat their bio-reactor with cells/proteins and then the add their constructs on top of this, suggesting an ideal way to induce polarity in the cultures.

3D printing and organisation of cells into a scaffold is definitely exciting, but it's not there yet.

Your last question is a very important one and it's something that every research group needs to decide upon. Are we trying to make an adult follicle that is already interacting (cycling etc...) and producing a hair shaft and implanting that, or are we attempting to mimic the embryonic events with a construct that is pulling in the surrounding tissues to make a follicle.

We are looking more at the 2nd question so our constructs could be thought of as the equivalent of the dermal cells in the embryo that are signalling to the epidermis to form a follicle. Obviously we can't test this using human embryos but we have data from the mouse embryo dermis which is applicable, and some of the factors that I talk about returning to the DS cells come from this data set.