Q&A with Dr. Aaron Gardner

[Trajan]

Professor Sinclair's Research

Dear Dr Gadrner,

Thankyou so much for replying to questions from forum members. I have a question regarding the research of Professors Fiona Watt and Rodney Sinclair. From what I remember these Professors have found that hair follicles in anagen phase increase the deposition of fat layers in the scalp as apposed to follicles in the telogen phase where fat deposition in the scalp is decreased. My question is do you think restoration of numerous follicles, by what ever means, which are able to achieve anagen, will help to restore the condition of the scalp?

[JZA70]

All this stuff seems so far away.

It is..

[deuce]

All this stuff seems so far away.

[joachim]

and another important thing:

do the DP cells lose their gene expression immediately after the first passage? or is then only part of it lost?

does it look like this:
- only 80% gene expression retained after passage 1
- only 50% gene expression retained after passage 2
- only 10% gene expression retained after passage 3
etc.
etc.
etc.

[joachim]

maybe a stupid question:

we're always talking about cell multiplication (expansion) in 2D only, which means we have isolated cells in a petri dish and let them duplicate themselves over weeks.
as far as i understand, the isolation of cells alone does not lead to the loss of gene expression. the loss only occurs if you start the 2D expansion process.

so what about the following thoughts: let's say we don't split the DP or the DSC to isolate the cells. so, when we have a whole intact DP and the whole intact DSC in a dish in front of us, we then see a lot of cells on the surface of those 3D clusters.
are we not able to tell these cells on the surface (with some proteins or other trigger tricks) that they should divide and multiply themselves? this would mean that more and more new cells pop up on the surface and the 3D cluster would grow and grow. after a few weeks we would still have an intact DP cluster which has e.g. 100 times the size of the initial DP =)
as the cells never were removed from their 3D sphere they always keep a connection to the inital cells, thus gene expression should not be lost. so the cells were multiplied but on an existing 3D cluster now.
and the next step: you can cut the big cluster into pieces now and isolate the single cells to form the new fully inductive DP spheres.

or is it really only possible to let cells multiply themselves if they are alone in the dish without any other surrounding cells?

[joachim]

Culture of the varying dermal populations is possible, dermal papilla, dermal sheath and inter-follicular dermal fibroblasts. These populations are also relatively easy to expand.

Epithelial cells are more tricky as they tend to terminally differentiate in culture (they are alive, but they do not multiply, they are also less likely to respond to inductive stimuli). Keratinocytes, outer root sheath and hair matrix epithelial cells are all able to be cultured.

Other cells such as melanocytes (for colouration), sebocytes (from the sebaceous gland) and immune system cells is also possible, but again their expansion potential is limited.

Dr. Gardner, i'm not sure if i understood the part with epithelial cells correctly.
you say epithelial cells are tricky because they differentiate and do not multiply.
does that mean you have a method to overcome this problem or are you not able to multiply them actually? if you're able to expand them, do they also lose gene expression or is gene expression no issue here with this cells?

i just tried to understand if Dr. Xu's breakthrough (creating unlimited epithelial cells by converting from iPS cells) is required for us now or if you are anyway able to already expand them with your own methods.

[sdsurfin]

Thanks dr.
I know you said you were against funding one researcher, but would it really be unrealistic to crowdfund your team or another top team? Not sure if you guys are lacking funding at all. What do you make of follica not being able to secure funds? Do you think that it is because their technique isn't good enough? Or do you think that dr cotsarellis was just angling for more money?

Also, I'm very curious, is someone intensely looking into what makes mouse and human DP cells act differently? It seems like the mysteries of regeneration lie in these disparities. Might it be possible to sequence the genes in a mouse and a human DP cell and at some point actually alter the DNA of DP cultures for each patient? On a perhaps more simple level- is it maybe a possibility to select out the DP cells that are better are aggregating and inductivity, and keep culturing them in order to perfect the cells that are to be used for implantation? Like selective breeding?

It seems that the two issues that have to be perfected are the mix of cells used, and the design and chemical nature of the culturing environment. I'm happy that so many teams are working on both parts. Are an embryo's or fetuses or babies dp cells more prone to induce hairs? I wonder if even the DP cells in our donor zone lose this characteristic over time. In mice hair is so crucial to survival that maybe their cells are programmed to lose this capacity at a slower rate(and they also live short lives). I wonder if making New DP cells from IPs cells will result in them having better inductivity...

[hellouser]

We, as a group, don't have a treatment as such. The technique that Dr Higgins and Prof. Jahoda worked on is being trialled in Taiwan and there are other trials using different methods. If successful approval will then follow based on the guidelines in your/other countries.

This technique is not 100% inductive and is not a cure, such a thing currently does not exist. We are working on improving our model step by step, and we may get to that step, or another group may but I honestly can't give a timeline. I'm honestly not a fan of the 5 more years statement, it will come when it comes and people are working towards it is the best I can offer.

Other than funding through methods like crowdfunding, is there any way in which the hair loss community, people like us from the forums and all around the world, can do to help speeding up the process for the 'holy grail' ?

[nameless]

Dr. Gardner since it's known that injecting cells can prompt hair to grow using the follicles that already exist in the skin, wouldn't it be better to focus on how to produce hair cells with good inductivity and then injecting those cells into the skin so they can prompt hair to grow through the existing follicles rather than focusing on how to grow whole follicles and then having to implant the whole follicle into the skin?

If you inject the cells instead of whole follicles then you are able to grow the hairs through the follicles that are already in the skin which would solve a lot of problems that come up when you inject whole follicles into the skin.

[nameless]

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.

Who is the Lendl group. I have not of them before you mentioning them. How far along are they at restoring inductivity?

[nameless]

Multi-cell models including adipocytes (fat cells) and melanocytes (cells that provide colouration) are in the works, but I can’t talk about those at the moment .

I'm highly interested in your multi-cell models, specifically the models that involve fat cells. I know you said you can't talk about those at the moment but please tell us when you can talk about those because I think that the signaling from the fat cells to the follicles could be part of what creates the hair inducitivity with hair cells. And since the fat cells are reduced in thinning areas that seems to mean that you will have to get more fat cells into the recipient area along with the hair cells.

[Artha]

Bottom line guys, there will be a better treatment in the future. Its just a matter of years so do your thing and get use to have a full head of hair already!

[agardner]

I didn't read through all twelve pages but did anyone ask our good friend Aaron when this "treatment" could be available to the public ?

We, as a group, don't have a treatment as such. The technique that Dr Higgins and Prof. Jahoda worked on is being trialled in Taiwan and there are other trials using different methods. If successful approval will then follow based on the guidelines in your/other countries.

This technique is not 100% inductive and is not a cure, such a thing currently does not exist. We are working on improving our model step by step, and we may get to that step, or another group may but I honestly can't give a timeline. I'm honestly not a fan of the 5 more years statement, it will come when it comes and people are working towards it is the best I can offer.

[agardner]

Any underlying hurdles with follicle maintentance will be completely eliminated, when we combine these future therapies with a traditional hair transplant. The donor area of a person provides plenty of healthy hairs, which can be traditionally transplanted on the top of a person's head. We will just then use the cloning method to put hair back into the hairless "gaps" in the donor resulting from the transplantation surgery. No need for maintenance after that, right?

It depends entirely in what form any cure for underlying issues comes in. It could be a single hit fix or at the other end something that requires repeated application. Since this doesn't exist yet we don't really know.

I would envisage that only a few follicles would be isolated as these would be sufficient to generate the required new follicles for the entire scalp, but again we need to wait for data from the clinical trials.

[agardner]

mr. Gardner thanks very much for your input...i want to ask the same question like one of other posters...please answer...can you tell us why in the first place aga happens, why pattern, why for someone starts earlier and someone later...why exactly this hair fall today and not hair near that...and why is everybody working on the end of the story (making lab follicles)...why are all teams working on giving signal to cells to make follicles...why cant we make body to give signal to cells to make follicles like in healthy scalp or just to stop attacking follicles...what is problem? sorry for this kind of questions but i think that a lot of people here dont understand science like me and we need this kind of answers...sorry for english its not my native language... thanks again!

There are numerous reasons, and there will often be numerous causes within a patient. Although not something I would usually recommend the wikipedia page actually covers a broad range of accepted causes:

http://en.wikipedia.org/wiki/Hair_loss#Causes

There are numerous groups (see the alopecia sessions from the WCHR2014 when the videos are uploaded) working on understanding the underlying issues and these are the groups that will produce a cure that prevents follicle degradation. However, this won't bring back follicles that have already been lost, hence why other groups are looking at generating follicles that can be implanted. Ideally both will go together, restoring follicles and then preventing their loss.