Home | News | Find a Doctor | Ask a Question | Free

Tissue Engineering of Hair Follicles: new research by Jahoda & Christiano


#1

https://www.nature.com/articles/s41467-018-07579-y


#2

Interesting and promising.

“that it represented an intermediate thickness between human terminal and vellus hair.”

That’s unfortunate. Sounds like it is producing something along the lines of the fine hairs on the nape of the neck.

What are your thoughts, Roger?


#4

“that it represented an intermediate thickness between human terminal and vellus hair.”

@RickH This is interesting, because this is EXACTLY what I predicted would be the case with the first generation of tissue-engineered hair follicles – they will be somewhere between normal healthy terminal hair follicles of a non-balding person, and vellus follicles.

Still, as I mentioned, I do think this could be quite beneficial. For most balding people and people who are mostly bald, what they need (most), is real, living hair to cover the bald spot(s) on their scalps, with sufficient hair-to-hair density.

Most topicals never get them far enough to cover their entire bald area with cosmetically decent looking follicles.

I think the follicles generated this way will be useful. Especially if the implanted hairs are spaced with sufficient density (which will actually be doable, since there is no real limit to how many new follicles they can grow), and you cut your hair really short (either a buzz-cut or maybe about 1 inch long), it will be really hard for people to see that the follicles aren’t of the normal healthy type with thick shafts that you see in people with lush heads of hair.

And guess what? Very short hair styles, like buzz cuts and slightly longer cuts are very popular now. I’d consider myself very lucky to be able to sport one of those cuts, if my entire bald/balding area could be covered.

I do think that subsequent to this, later generations of these in vitro “lab grown follicles” will be better and better - more closely approximating a normal healthy hair shaft.

But I think this is a great development, and I’d MUCH rather have these kind of “intermediate” thickness, slightly weak looking follicles, as long as the density is good, than no hair or the almost bald look my scalp has now.

To address your key point, though - I think they will probably look better than the hairs on the nape of your neck. Those are more-or-less vellus follicles. I think the hair will be interemediate between those and the normal hairs of a non-balding person’s scalp.

Incidentally, I suspect the same thing will be true of Dr. Tsuji’s procedure.


#5

You see, that’s exactly what I kept telling to myself and others that preservation of cells inductivity is the most important issue, challenge. In this case DPC, in Shiseido – DSC and in Tsuji – epithelial cells +.
Reading this article you realize how complex is to achieve that and how much more complex is going to be for Tsuji to achieve that with more types of cells involved. It would be very interesting to know Shiseido and Tsuji approaches towards solving inductivity issues. But I think exactly the process of inductivity preservation is what makes the biggest asset of the company. Therefore everyone will keep it propriatery as to how exactly they do this.
One thing that baffles me is that even if you get a dose of freshly inductive DP cells, it will only work if you still have functional bulge stem cells that are ultimately responsible for normal hair cycle. I wonder would inductive DP cells somehow be able to restore defunct bulge stem cells. As we know from Cotsarelis works, that bulge stem cells are intact but defunct in balding people’s scalp.


#7

The confusing thing about this article is that they keep on mixing up a discussion of two pretty different lines of research: Jahoda/Christiano’s work on 3D culturing, and the 3D printing into a well stuff.

Preservation of cells’ inductivity is a problem, but only when trying to induce existing miniaturized follicles to grow, or when (as Jahoda and Christiano worked on, and which they keep mentioning in this article), when doing something like growing HF from 3D cultured DPCs. In those cases, you’re only relying on the inductivity of DP cells, and inductivity is lost the more you culture them (even though the 3D cultures preserved around 22% of the genes they say are activated in fully-inductive non-cultured cells.)

With Tsuji’s work, I think you’re wrong, because he’s using a different means to generate hair follicles (different from the 3D cultured cells, but the same as the other work described in this article). What he’s doing is recapitulating the ectodermal (epidermis) -mesodermal (dermis) interface in the developing embryo. This is the mechanism the embryo uses to grow its brand new hair follicles. No inductivity is needed there, because the chemical interactions at the junction are enough to induce a brand new hair follicle to develop.

I notice in this article, they kind of avoid mentioning too much about what Dr. Tsuji’s doing, as if not to step on his toes. They discuss recapitulation, but don’t say they’re copying Dr. Tsuji’s work. When in fact, if you read this carefully, I think they are, because they’re using “wells” in which to place the cells on top of each other, to get a “100:1 aspect ratio”. That means that inside these wells, they have a column of cells 100 times as high as it is wide. They talk about supplementing that in the future with a very precise arrangement of all the constituent cells in the follicle (of which there are actually many types). So, they’re mixing in a lot of stuff about their 3D spherical DPC cultures, in which inductivity is very important, with a discussion of 3D printing with multiple cell types in a well, in which inductivity is not important because the mix of cells is supposed to do everything together. But they don’t explicitly mention that in this part of their work they’re just attempting to do the same research Dr. Tsuji is doing.


#8

I agree that it is confusing. It could be the case that different researchers use different terminology at this moment in time.

With regards to Tsuji method, they do pluck off hair follicles and they do further dissociate cells and they do culture them. Yes, they don’t use DP cells (as far as I can figure out). As you mentioned, they use three other types of cells but they do have to “multiply” them to get ratio. Otherwise how this treatment would have advantage over ordinary HT? So, once you dissociate cells from their natural environment, BANG!!! - you’re dealing with loss of trichogenic properties of a cell. This Jahoda/Cristiano method involves as they call it “recapitulation” that is genetic reprogramming of cells using Lef-1 and similar in order to recover inductivity that 3D culturing alone cannot achieve.

I might be wrong but I think I’m right.

With regards to 3D culturing and 3D printing, I think you’re slightly mistaken. 3D culturing is the stage in the process when all relevant extracted cells are being “multiplied” to a necessary amount. 3D printing using “wells” (Tsuji’s fancy word) or 3D molding prints (Jahoda&Christiano fancy word) is stage when those “multiplied” cells are positioned in an appropriate way in order to generate hair primordium, hair follicle. So those two are not different research lines but different stages of a process.

I also think that they are not necessarily copying Tsuji but exploring research line very similar to that of Tsuji/Ricken. In fact I can’t see them explicitly saying they’re only using DP cells while creating HF. Mostly article addresses DP cells’ inductivity issue. And I don’t think they are doing anything particularly illegal.

I also think this research is somehow connected to HairClone. One of their key scientific advisors Dr. Claire Higgins has worked with Dr. C.Jahoda and Dr. A.Christiano. On top of that Dr. Paul Kemp talks about two different research lines at HairClone: 1.using cultured DP cells to rejuvenate HF. This procedure according to them will be offered next year, 2. creating HF deNovo most likely using techniques similar to those of Tsuji or this one.


#9

Roger

  1. Does this new information more or less optimistic about hair loss cures in the near future. It makes me feel more positive about near future hair loss treatments.

  2. It sounds like they’re making some kind of intermediate thickness follicles. Do they have a plan to increase the thickness so they make full thickness follicles?

  3. I think Jahoda created intermediate thickness follicles a few years ago by way of 3-d platforms but it only worked some times and when it did work it only created weak follicles because the cells only preserved a small fraction of inductivity. It sounds like Jahoda is still stuck in that same place.

  4. Does this seem to you like it bodes well for Tsuji’s efforts or not? If all Tsuji can do is create intermediate thickness follicles that is not a good thing IMO. People want full thickness follicles.


#11

@jarjarbinx

To answer your main question, if I have to guess I think that both Jahoda/Christiano (the team in this article) and also probably Tsuji, will be creating some kind of intermediate thickness follicles currently. Do I think they want to develop something better than that? Yes, I think they’re trying to move in that direction with additional research. Would I be happy to get intermediate thickness follicles? ABSOLUTELY. Bring it on and bring it on as soon as possible. All I want is real hair to cover my scalp. If the hairs don’t look great, I’ll address that condition by cutting and styling it in a way that minimizes those problems. In particular, cutting it really short. I think it will still look like great coverage.

To answer @Otter’s issues above, I do think these are two different lines of research, but the Jahoda/Christiano team has decided to talk about them together in their article because they’re closely related and they probably regard one as an extension of another.

Initially, Jahoda and Christiano were doing 3D hanging cultures of cells to increase the inductivity of DPCs because they deduced that the normal, flat (petri dish) cell culture was not a natural environment like in the body, and was causing the cells to loose their inductive ability. So they thought of hanging 3D cultures as a way of “tricking” the cells into thinking they were in the body, in a natural environment, one which would not cause them to lose inductiveness. The end goal was to have inductive DP cells that could be injected into the scalp, to induce existing miniaturized hair follicles to grow into terminal ones (the same concept which Intercytex and Aderans failed at because their cultured cells didn’t have sufficient inductivity).

The Tsuji procedure, in my view, is a completely different. It’s a completely different concept, which uses the natural ectoderm-mesoderm interface in embryonic development of hair follicles (look this up if you don’t know what I’m talking about) to generate completely new follicles. I think with this method, you don’t have to worry about inductivity at all, because of 2 things:

  1. You’re using more than 1 cell type; and
  2. You’re placing the different cell types one above the other, exactly as they occur in the embryo, to get them to recognize each other and signal to each other, which is the trigger that causes spontaneous hair follicle development

So in the Tsuji procedure, it’s a workaround that doesn’t require the cells to be too inductive. The other components - different types of cells interacting with each other - provide that trigger themselves. So, even if you have to culture the cells, there is not much of a concern about lost inductivity. I think they included discussion of the earlier Jahoda/Christiano work with 3D cultures in this article to recognize the work of Jahoda and Christiano, because they are now part of this team, and there is some relevance of that earlier work to this work.

The team that wrote this article is a big group. It looks like Jahoda and Christiano found partners to combine their efforts. But their direction now seems to be more like Dr. Tsuji’s work. The old simple technique of 3D hanging cultures is now dead in the water, I think, because they reached a plateau at 22% of the genes behaving like fully inductive cells, but they couldn’t move beyond that (the 22% figure is from research done about 5 years ago, and if they were able to go higher than that, they would have reported the new data - but we see no new data - so I can infer from that they were not able to go higher).

So now, I think they have shifted over completely to methods which are extremely similar to Tsuji’s work in almost every way (different types of cells, wells, etc.) They are not going to come out explicitly and admit that they’re converging with Tsuji’s work, of course, but from a bird’s eye view, it kind of looks like that.

So I think both teams will produce a similar product.

But, I think that Tsuji will be out with his product clinically much sooner, because of the streamlined approval process for cell therapy and tissue engineering in Japan.


#12

For as long as 13 years I’ve been reading upon this subject of experimental research into hair regeneration and am perplexed as to why all of these promises havent ended up as prescription pills at the doc’s clinic for those of us who have been suffering from the dread of our shiners. Seriously its about time something new that doesnt smack of the same old rogaine gets some shelf life attention. Its almost 2020 and NOTHING new is over the horizon for the hair thinning public to consume. Come on already!!!


#13

I understand that the situation is terrible but isn’t it clear from the Tsuji reports, the Jahoda/Christiano reports, and even the Hairclone reports, that we are getting relatively close to a cure. I think we are now less than 2 years away to at least some limited commercialization.


#14

Given that you yourself say that Tsuji’s method is somewhat different from other research groups does that make you think that there’s at least a slight chance that Tsuji might produce full thickness terminal hairs? I do think so because slight technical differences can sometimes make big differences in outcomes. I think that if he’s doing things just a little bit better (and different) from what everyone else has done I think there’s a chance that might get his treatment over the wire. When push comes to shove there’s really only a little difference between an intermediate hair and a terminal hair.


#25

@jarjarbinx OK, I partly agree with you. I think there is a spectrum and these 2 research groups are both producing “intermediate” follicles, but they’re on different parts of the spectrum. If you look at the photos from the Jahoda/Christiano article, the follicles on the mouse’s back look quite thin (and also colorless or white), they look closer to the vellus end of the spectrum. Whereas if you look at the Tsuji mouse pictures from as early as 2012 that you can see here:

The Tsuji hairs look thicker, colored and more robust, still intermediate but a lot closer to the terminal end of the spectrum. I would say the Jahoda/Christiano group are latecomers to bioengineering hair follicles, and the differences we see in the photos may reflect where the 2 groups are at, respectively, in their progress with this technology.

I still think both will be “intermediate” though, because these are bioengineered follicles, and there is no way, in my mind, that the first generation of this technology will be able to produce extremely robust, perfect looking hair shafts. The way I see it, there are just too many variables outside of their control to do that right now. The follicles being created are not exactly like terminal follicles from a healthy, non-balding person. They are close replicas, but physically not exact replicas. Therefore, what follows is the hairs they produce will not be 100% robust looking. I could be wrong about this, but this is what common sense is telling me. I think the hair shafts will tend to have a thinner and wiry, not quite perfect look, like you see in the pictures, rather than a lush, super-healthy look like in a non-balding person with a good head of hair.

One application I see for this is also to supplement conventional hair transplants. You know I’m very skeptical of HT and HT doctors, but I do envision that these bioengineered hairs could be an incredible tool for them to use, in conjunction with regular HT. Bald areas could be first filled in with HT, then lots of bioengineered follicles could be planted between the transplants, to produce a much fuller, more natural look, with follicles of varying thicknesses. It would eliminate the biggest traditional problems of HT, the lack of sufficient donor supply and the “doll’s head” look where thick follicle units are interspersed with bald skin. The latter problem has supposedly been solved to a large extent with new transplant techniques like FUE/FUT, but it hasn’t been completely solved. This development could solve both problems.


#26

I also think that the hair Tsuji’s produced on the rodent looked wiry. That’s the only thing about Tsuji’s treatment that has me a little worried. I agree that Tsuji’s hairs looked kind of thick and have color. If he can get the wiry look out of those hairs then I think that his hairs will satisfy me.

Have you noticed that sometimes hair plugs produce wiry looking hairs? I noticed that in some before-and-afters. One doctor told me that this was caused by the plugs being separated from the blood supply. Do you think that Tsuji’s cells having been harvested from the donor area, and perhaps thereby being separated from the blood supply, could cause that wiry look? I don’t like it. And I know what you mean about people with their original hair having hair that looks lush. I think that wiry look is kind of course, which kills the lush look.


#31

I think the wiry quality of the hairs can be caused by a number of factors, including separation of cells (or in the case of HT, grafts) from the blood supply.

In the case of bioengineered follicles, the wiry look can also possibly be caused by the fact that the follicles they are growing just aren’t perfectly formed, the way a natural follicle would be in a healthy non-balding scalp.

Because these follicles are essentially being assembled in the lab from component parts, and didn’t develop themselves “in vivo” according to the genetic coding resulting from millions of years of human evolution, first generation bioengineered follicles may have slightly imperfect shape and dimensions. I think a lot of factors in the bioengineering process could affect the consistency and quality of the hairs. Maybe the follicles’ bulbs are imperfectly shaped. This might result in production of hairs that in addition to being a bit narrower than healthy terminal hairs, also have imperfect or unusual cross-sections. So, instead of a cross section which is round or oval (which results in the “lush” look, I believe), they may have varying cross-sections or slightly flatter cross-sections. This could affect the macroscopic cosmetic appearance of the hair shafts and could possibly result in shafts which are slightly curled, coarse, oddly shaped or having other differences, such as anomalies in the 3 layers of the hair shaft - the cuticle, the cortex and the medulla (see these articles for descriptions):

https://www.philipkingsley.co.uk/hair-guide/hair-science/the-hair-structure

https://www.hshairclinic.co.uk/hair-loss/all-about-hair/hair-structure/

Personally I’m not super concerned about all this, because I think the prospect of bioengineered hair follicles will permit - for the first time ever - a truly unlimited hair supply. Like I said, if I were concerned the individual hairs didn’t have a great cosmetic look, or looked too wiry, I could console myself by knowing that they could be spaced very close together, giving a high-density look that could still be styled short, in a number of ways. See some of these examples and tell me what you think:


#32

I agree that styling techniques and having lots of new follicles close together could solve some of the wiry problems. And perhaps blow drying on the light heat setting could help get the wiry look out too. I’m hoping to grow my hair long though.

Do you know anything about when Tsuji’s human studies will begin. I would like to see this train coming. I want to see the results asap.


#33

I’ve seen a date of March 2019 referring to Tsuji’s human trials, but that was announced sometime last year. I don’t know if they’re still on schedule to do that.


#34

Are you excited about Tsuji’s treatment? Have you made some guesstimates of cost for Tsuji’s treatment when it hits the market? I’m thinking $30,000 to $50,000. What do you think?


#37

I don’t know what the going rate for HT is these days, because I haven’t been interested in HT up until now, but you’re probably in the ballpark with those numbers. Remember, after extraction of the donor follicles, the first few steps of the process involve some pretty sophisticated lab manipulations. And then the final steps involve implantation - which has to be done by a HT surgeon, there is no way of getting around that. The implantation steps are exactly the same as HT surgery, and require the exact same skills. So yes, it’s going to cost AT LEAST as much as a regular HT, and the more scalp you have to cover, the higher the price tag.

I think the great thing about this is that HT surgeons should become huge advocates of it, because they will be doing the most visible parts of the work. Therefore once they find out how this will benefit them financially - by bringing in massive numbers of new patients who had previously been wary of HT - they will be using all their power to push this through the FDA.


#38

Does the robot implantation technology produce better results than living hair transplant surgeons do? If the answer is yes then maybe their could be some savings by using robots to do the implantation. I hate the idea of being at the mercy of the surgeon because some are good, others are bad, and they all publicize their best results, not their worse results.


#42

When you have an unlimited donor supply from HM or bioengineering there is much more room for error, and also less hair has to be removed from the donor area. The main reasons for botched HT surgery are:

(1) visible scars at donor site, and
(2) hairs look too sparse at recipient site.

With any technique that provides unlimited supply, the chances of completely botching the surgery will be almost nil for most surgeons. Almost any problem like the ones above can be fixed by just adding more hair.

I don’t know anything about robotic HT, I think this is not in wide use yet.