Donations to the Sanford-Burnham Medical Research Institute

Stem cell; cell based hair therapy
21

Good question, but I would guess it doesn’t have anything to do with Follica’s wounding protocol (which they licensed from Dr. Cotsarelis). I think these are 2 separate ventures, both business wise and conceptually. If Cots wanted to augment the PGD2 blocker with wounding, and he had an exclusive agreement with Follica for the wounding part, he would have to abrogate or rescind that agreement with Follica and that would be very hard to do.

If Follica has been relatively silent since this hit, I think it’s more because PGD2 is where Cots’ attention has been going these past 2 years and Follica may be resigned to the fact that they’ve stalled and others are moving well beyond them.

I think the PGD2 blocker thing is meant to be a separate protocol from the wounding idea, and they’re not related other than the fact that they were both based on Dr. Cotsarelis’ research. The PGD2 blocker thing is meant to work on its own.

Another thing about Follica and wounding is that I think that any procedures involving wounding are now obsolete. The existing science has moved well beyond that. Wounding was only ever relevant because it unleashed growth factors in the skin that would have been provided by activated stem cells. Wounding became relevant because nobody really knew how to use pluripotent stem cells. They were hard to culture, it was very hard to get permission to use them, and they couldn’t be manipulated, at least not with the technology that was around a few years ago. But now researchers are actually using stem cells themselves. So wounding procedures have been rendered obsolete. Wounding is “yesterday’s news”.

Thanks for posting that and finding all this interesting stuff for us…

22

OK, but if you look at his paper (which is published online in perfect English, in fact it’s pretty well-written), he says that the ONLY role of the fat layer is to physically cushion the hair follicle from gravity. He makes no mention that the fat layer is secreting any kind of chemicals or growth factors that contribute to hair growth. I would think that if he thought that, he would at least mention it in his paper. Yet my recollection is that he makes no mention of it. In fact, in the beginning of the paper he kind of ridicules any theory that asserts that the real reason for hairloss is totally biochemical.

There are so many logical holes in his paper, and scientific faults, it is hard to go through them all. I have a BS in biochemistry, several years of graduate school and am working on a MS in biotechnology. There are many fallacies in Dr. Ustuner’s paper, although it is well-written – and I can respect him and kind of understand how he came to those conclusions, because he is a plastic surgeon and his skills and knowledge are primarily in “lifting tissues” – that’s why he sees almost everything in terms of gravity’s downward pull.

One of the biggest fallacies in Dr. Ustuner’s paper, which I and several people called him out on when he came here to this forum, is that he questions how DHT could rise in balding areas of the scalp, while in other areas of the body, DHT actually contributes to hair growth, and not to hair loss. He used that as the crux of his argument that the real reason for hair loss is not DHT. But he totally failed to consider something which is very well-known to biochemists – the positive feedback loop where (one example) a certain enzyme (like 5-alpha reductase) can be stimulated under certain circumstances to generate more of its product. The below quote is from Wikipedia:

“In contrast to negative feedback, positive feedback occurs when an output is used as a signal to increase further response of the output. In other words, if process A results in consequence B, B reinforces process A, resulting in a cascade where more of B occurs, which causes more of A to occur, and so on. An example of a positive feedback loop is evolution, where an organism evolves and becomes better at hunting prey, for example, prey evolve better defense mechanism like faster running, which causes predators to adapt by evolving better chasing skills, and so forth. Note that a positive or negative feedback mechanism is not necessarily beneficial or harmful; they only refer to the mechanism by which inhibition or propagation occurs.”

From Wikipedia article -

http://en.wikibooks.org/wiki/Structural_Biochemistry/Enzyme_Regulation/Feedback_inhibition

Then when we reminded him about this phenomenon here in the forum he said yes, he knows about it (as any MD would be expected to), but was unable to say why he neglected to consider it in his paper.

Don’t get me wrong, he’s a very smart man. I just think he’s dead wrong on this and he’s being stubborn because he feels he’s come up with a clever theory, but I believe on close scrutiny, it’s an indefensible one.

23

I don’t have the scientific background to debate you, but I’m more concerned about whether his conclusion that a scalp needs healthy adipose tissue to grow hair (regardless of how he arrived at it) suggests that any cure on the cellular level is doomed if the damaged scalp environment isn’t also repaired.

IOW, can a pill like one we are discussing in this thread overcome the fatty tissue issue?

-ESP

24

Good question and I agree with you that a good scalp environmentt, containing fat, is necessary to grow hair. But Dr. Ustuner’ s theory is completely different from the Yale study. They may look superficially the same because they both reach a similar conclusion (fat tissue is good for hair), but the similarity ends there.

I actually agree with Jarjar and you about the importance of fat, with one caveat: I don’t think that not addressing the fat issue is going to stop a cell-based procedure from growing cosmetically-adequate terminal hair on the heads of moat people. Most balding people still have enough fat in their scalps to grow hair if they have activated stem cells. It may only weigh in as an absolutely necessary factor in a small percentage of extreme outliers whose fat layer has been totally wiped clean. But I don’t think this happens in most people with MPB. I think this process is very slow. The vast majority of balding people still have enough fat in their scalps to support a good amount of hair growth when cells are injected.

It’s not that I don’t think far is a factor. It’s that I think Jarjar is overemphasizing fat as a factor, because the fat hasn’t been totally depleted in most balding people. It’s not like cell-based therapies are not going to grow hair in most people because they don’t have enough fat anymore.

25

[quote][postedby]Originally Posted by roger_that[/postedby]
Good question and I agree with you that a good scalp environment, containing fat, is necessary to grow hair.

I actually agree with Jarjar and you about the importance of fat, with one caveat: I don’t think that not addressing the fat issue is going to stop a cell-based procedure from growing cosmetically-adequate terminal hair on the heads of moat people. Most balding people still have enough fat in their scalps to grow hair if they have activated stem cells.[/quote]

Roger, it appears that the reason your already-existing miniaturized follicles are stuck miniaturized is because the miniaturized follicles are receiving an insufficient amount of growth factors to produce larger healthier follicles. The growth factors come from the fat layer and since the overall fat layer has reduced that results in a reduction in the overall amount of growth factors that the fat layer produces and sends to the follicles. Why wouldn’t cell-based cloned follicles need the same amount of growth factors that your already-existing miniaturized follicles need?

It sounds like you’re saying that unlike your already-existing miniaturized follicles, cell-based cloned follicles would be free from needing the same minimum amount of these growth factors for some reason. Why would cell-based cloned follicles require less growth factors than the miniaturized follicles that you already have?

In my view, if there isn’t enough growth factors being supplied to your already miniaturized follicles to sustain healthy growth then there probably isn’t enough growth factors to sustain healthy growth in implanted cell-based hair follicles either.

And if you are going to add to the underlying fat layer surgically or inject growth factors in order to get more growth factors to implanted cell-based cloned follicles then why not just skip the whole cell-based cloned follicles part of the equation and just implant fat tissue in the scalp NOW or inject growth factors so that your already-existing miniaturized can receive more of the growth factors they need to produce larger healthier follicles?

26

I’m not saying that at all. I agree with you; growth factors are just as important for the health of normally growing hair as they would be for cloned hair.

What I’m saying is that just because you don’t address the fat issue, it doesn’t follow that if you inject DP cells grown from stem cells, they won’t actually grow into follicles in your scalp.

Think of it this way: how do healthy follicles grow and cycle? Signals from stem cells at the HF bulge and also in the fat layer. What injecting inductive DP cells does is to “skip this step” by jump starting the process – flooding your scalp with the inductive DP cells that they WOULD HAVE HAD if they had the proper healthy signalling from the stem cells.

Once that step is provided, you will grow hair. Now, to keep it up and running, and to continue growing well, yes – NOW they need to have that continual healthy signalling environment. Replenishing growth factors, either by adding them from exogenous sources, or by adding to fat (with adipose stem cells) will take care if that part.

You seem to be saying that unless you address the fat issue FIRST, Dr. Terskikh can inject all the inductive DP cells he can get his hands on, and no hair follicles will grow in your scalp, and I think that’s wrong.

27

Ok, next question:

A while back, someone suggested that the life of a follicle has a finite number of cycles (I think it was Ahab, but not sure).

Assuming this is true, how do you think it the daily (or frequent) administration of an exogenous source that provides
the nutrients required to sustain vibrant growth will affect the duration of a “cure”?

28

Even if we assume that there’s an inherent limit to the number of cycles, I would say it doesn’t disadvantage any of the approaches we’re discussing here for a couple of reasons:

  1. At what point do you start counting the cycles? Sanford-Burnham is growing brand new DP cells directly from pluripotent stem cells – in other words, a new line of DP cells that has never been involved in cycling before. So do you start counting their cycles from the time they generated the new follicles? Or if they induce a miniaturized follicle to regrow and revive it, do you start counting the cycles from that point onward? Or by averaging the old follicle with the new cells? If we get to “reset the clock” now because these DP cells are “fresh”, then you’ve just bought yourself a lot of extra time for these follicles.

  2. You’re suggesting something like, if you use growth factors too much or too often, you’ll kick the cycling into something like an “overdrive”, and then the follicles won’t last as long (assuming a direct relationship between the amount of growth factor used and cycling rate). In this case the follicles expire sooner because cycling has become too rapid and you’ve accelerated their aging. Well, perhaps – we really don’t know. This idea of a “finite number of cycles” is conjecture because I believe nobody’s ever counted. It might be true, though. But, assuming it is true --then, if you add too much growth factor and you see the cycles starting to accelerate, you can do two things: You can reduce the dosage so cycling slows down again (problem solved) or you can just inject new Sanford-Burnham DP cells when those follicles have aged out, causing new follicles to grow. As long as you have access to adult pluripotent stem cells, you can ALWAYS make a fresh supply of inductive DP cells and repeat treatment. (Again, problem solved).

29

To add subcutaneous fat, you don’t have to do it surgically, all you have to do is inject fat into the skin just below the epidermis. I guess the fat could be taken from liposuctioned fat from other areas of the body. Many doctors are injecting fat all over the body right now in cosmetic procedures – for instance, to smooth out wrinkles on the face, to increase the size of women’s breasts and butts, etc.

I agree with you, subcutaneous fat is very important, and does provide growth factors and signalling. But somehow I really doubt that if you take a person who’s bald, say a NW5 or NW6, and just inject fat into his scalp, that he’s going to start growing hair.

To me, if it were this easy, this would have been discovered a long time ago and doctors would be doing it all over the place right now. You seem to think that just having fat in the scalp is somehow a magic bullet that will produce a full head of hair. It’s not. It’s one part of the whole equation.

Yes, subcutaneous fat provides growth factors and creates a healthy environment for hair to grow, but the real key growth factors (which are much the same growth factors) come directly from activated stem cells and progenitor cells right at the hair follicle. These send chemical signals to the dermal papilla that tell it to cycle, and the stem cells differentiate into DP cells which proliferate causing the hair to grow.

30

Maybe the fat cells have disappeared because the follicle has miniaturized. Transplanted hair has no problem growing. Love to see before and after test of transplanted hair to verify fat content.

31

So you’re saying there may be a two-way feedback loop going on between the follicles and the fat layer, in that the fat layer helps the follicles to grow, and conversely the presence of terminal follicles in the skin somehow supports or promotes the fat layer. Interesting, and this is something that I had actually given some thought to.

I haven’t seen the second part – follicles themselves signaling the fat layer to stay healthy – anywhere in the literature or speculated on anywhere before, but there are many such 2-way feedback loops in the body. This is something to consider, and if I had to venture a guess, I’d say it’s correct.

32

It seems like common sense that the fat layer will be linked to cellular problem that triggers MPB in the first place, like a chain reaction. So you’d assume that when you fix the cellular problem, then the fat layer should start to rejuvenate as well.

33

Well, some people like Jarjar are saying that once the fat layer diminishes, just adding new inductive DP cells won’t rejuvenate the fat layer. But, as you suggested there, I suspect it’s more complicated than that. Knowing how the human body operates in very many cases, I suspect that the signaling is TWO-WAY, and that replenishing the cells and kick-starting hair follicles and the hair growth cycle again, will in turn signal back to the dermis and help to revive the fat layer.

34

[quote][postedby]Originally Posted by roger_that[/postedby]
To add subcutaneous fat, you don’t have to do it surgically, all you have to do is inject fat into the skin just below the epidermis. I guess the fat could be taken from liposuctioned fat from other areas of the body. Many doctors are injecting fat all over the body right now in cosmetic procedures – for instance, to smooth out wrinkles on the face, to increase the size of women’s breasts and butts, etc.

I agree with you, subcutaneous fat is very important, and does provide growth factors and signalling. But somehow I really doubt that if you take a person who’s bald, say a NW5 or NW6, and just inject fat into his scalp, that he’s going to start growing hair.

To me, if it were this easy, this would have been discovered a long time ago and doctors would be doing it all over the place right now. You seem to think that just having fat in the scalp is somehow a magic bullet that will produce a full head of hair. It’s not. It’s one part of the whole equation.

Yes, subcutaneous fat provides growth factors and creates a healthy environment for hair to grow, but the real key growth factors (which are much the same growth factors) come directly from activated stem cells and progenitor cells right at the hair follicle. These send chemical signals to the dermal papilla that tell it to cycle, and the stem cells differentiate into DP cells which proliferate causing the hair to grow.[/quote]

Roger in your last paragraph above you mention “ACTIVATED STEM CELLS.” What exactly do you mean when you say the word “ACTIVATED”? And exactly how do these stem cells become “ACTIVATED” in the first place? Yale seems to think that the growh factors from ADSCs could be what “ACTIVATES” those stem cells?

In the article below YALE say it’s their thinking that the adipose derived stem cells send signals to those cells at the base of follicles - what you call “activated stem cells and progenitor cells.”

Yes, I do think that there’s a chance that simply putting fat tissue (loaded with ADSCs) into the correct depth of the scalp might get NW4 and NW5 to start growing hair.

By the way, Yale also said that when hair stops growing the fat layer in the skin is reduced and when hair is growing the fat layer in the skin is increased. Gee!!!

35

I think that there is probably cross-talk between the ADSCs and the cells at the base of the follicles, which results in hair growth. I think it requires a sufficient amount of both ends of the conversation. You have the cells at the base of the follicles. What you need is more signals from your fat layer. You have insufficient signals coming from your fat layer because your fat layer has reduced. Less fat layer = less fat signaling.

36

[quote][postedby]Originally Posted by roger_that[/postedby]
Well, some people like Jarjar are saying that once the fat layer diminishes, just adding new inductive DP cells won’t rejuvenate the fat layer. But, as you suggested there, I suspect it’s more complicated than that. Knowing how the human body operates in very many cases, I suspect that the signaling is TWO-WAY, and that replenishing the cells and kick-starting hair follicles and the hair growth cycle again, will in turn signal back to the dermis and help to revive the fat layer.[/quote]

So what you’re saying is that using cells to produce follicles will force the skin to produce more fat but I think that the evidence shows that things work the other way around. I think the evidence shows that adding fat forces the cells to morph into follicles and enlarge follicles. Both AAPE and Histogen’s HSC constitute the signals from fat tissue and both AAPE and HSC prompt follicles to grow. This supports my position and it suggests that you’re focused on fixing the wrong side of the equation.

37

[quote][postedby]Originally Posted by roger_that[/postedby]
Think of it this way: how do healthy follicles grow and cycle? Signals from stem cells at the HF bulge and also in the fat layer. What injecting inductive DP cells does is to “skip this step” by jump starting the process – flooding your scalp with the inductive DP cells that they WOULD HAVE HAD if they had the proper healthy signalling from the stem cells.
[/quote]

Even if you’re right the resulting hair would just be peach fuzz like we already have. We don’t want peach fuzz. We want longer, thicker, pigmented hairs. You need more ADSC growth factors to lengthen and thicken the new peach fuzz into hair. And if you’re going to use ADSC growth factors to turn the new peach fuzz into longer thicker hairs why not just turn your presently existing peach fuzz into longer thicker hairs?

38

[quote][postedby]Originally Posted by roger_that[/postedby]
You seem to be saying that unless you address the fat issue FIRST, Dr. Terskikh can inject all the inductive DP cells he can get his hands on, and no hair follicles will grow in your scalp, and I think that’s wrong.[/quote]

I’m not suggesting it; I’m saying it. And by the way so is Dr. Gardner and by extension so is Dr. Jahoda.

Why would Dr. Terskikh’s follicles grow to a satisfying length and thickness when your own already existing follicles won’t? There isn’t enough growth factors in your skin to nourish Dr. Terskikh’s follicles just like there isn’t enough growth factors in your skin to nourish your already existing follicles (peach fuzz follicles). If you think that there is enough ADSC growth factors to grow satisfying hairs from Dr. Terskikh’s follicles then you are saying that Dr. Terskikh’s follicles need less ADSC growth factors than your own natural follicles for some as-of-yet unexplained reason.

39

[quote][postedby]Originally Posted by roger_that[/postedby]
To add subcutaneous fat, you don’t have to do it surgically, all you have to do is inject fat into the skin just below the epidermis. I guess the fat could be taken from liposuctioned fat from other areas of the body. Many doctors are injecting fat all over the body right now in cosmetic procedures – for instance, to smooth out wrinkles on the face, to increase the size of women’s breasts and butts, etc.

I agree with you, subcutaneous fat is very important, and does provide growth factors and signalling. But somehow I really doubt that if you take a person who’s bald, say a NW5 or NW6, and just inject fat into his scalp, that he’s going to start growing hair.

To me, if it were this easy, this would have been discovered a long time ago and doctors would be doing it all over the place right now. You seem to think that just having fat in the scalp is somehow a magic bullet that will produce a full head of hair. It’s not. It’s one part of the whole equation.
[/quote]

There has not been a single experiment involving the implantation of fat tissue (with a robust amount of ADSCs) into thinning scalp skin at the correct depth and location of the scalp to grow hair. Not even one. I do think that it would probably grow hair if PERMANENT fat tissue with lots of ADSCs was used and if it was put at the correct depth and location. It also has to implanted in such a way that it stays put. Injected ADSCs do not stay put. The cells migrate from the injected location.

Why wouldn’t implanting fat tissue as I’ve described grow hair? Injecting ADSC growth factors grows hair (see Histogen’s HSC studies and AAPE studies) and implanting permanent fat tissue at the right depth and location would be an even better treatment because implanted fat tissue would give off growth factors continuously where injections of Histogen’s HSC and AAPE only give the follicles those growth factors at the time of the injections.

40

I realize that, I’m saying I think the signaling goes both ways. It goes back and forth. So, signals from the fat layer promote hair growth, AND signals from the terminal, cycling follicles also induce the fat layer to remain healthy and in place.

This scenario of a two way feedback mechanism is quite common in human physiology. That’s why I think it may apply here. There are all kinds of 2-way feedback loops in the body, some hormonal - the thyroid and adrenal glands - some with respect to the kidneys and bone marrow.

I think, and granted, this is speculation but informed speculation, that if you induce new terminal follicles to grow in the scalp (by injecting cells), you’ll find that the new terminal follicles (or rejuvenated follicles, miniaturized ones that have been enlarged), in turn begin to send biochemical signals back to the dermis, to start slowly restoring the fat layer.

I’m saying it may be a two-way street, with signaling going back and forth, both the fat layer and the terminal hair follicles supporting each other.