@Footy - you are proposing a connection between DHT and the scalp’s lymphatic drainage system, but you haven’t provided a potential mechanism for this. Do you have any citations showing there’s a direct connection, and how would this work biochemically? Has it been established that DHT bonds with androgen receptors on lymph vessels in the scalp and influences their morphology or function?
Good questions Roger_ that.
My conclusion here is based upon the layout of the superficial lymphatic system, and the areas of increased hair growth induced by DHT. This also involves a consideration of how the lymphatic vessels move tissue fluid, and where most of the bodies DHT is produced. Also what really matters is proving an in-vivo effect of DHT upon lymphatic efficiency. There is an existing in-vivo study that found significant gender differences in lymphatic efficiency, and the same kind of study could confirm if DHT is responsible for this gender difference.
I think most people would agree that there is more of a direct link with the amount of DHT, and the amount of body hair growth. It is the scalp hair loss effect that is not consistent, in that you can have high levels of DHT and body hair, and either lose scalp hair or not. I think this is explained by fluid dynamics.
Increased lymphatic drainage in men would increase nutrient supply and waste removal. This would increase tissue building capacity, performance and endurance, all very useful in terms of androgenic effects. Lymph vessels move tissue fluid by contractions of the vessels, the abundant one way valves in these close when the vessels contract directing the fluid ultimately back into the main circulation.
The only logical way to increase lymphatic drainage, is to increase the natural rate of the vessel contractions. But because of the one way valves, you would have to be careful where you introduced a substance in the body designed to increase the contractions.
Most of such a substance would have to be feed into the lymph vessels at the extremities of the lymphatic system, in order to get an even increase throughout the system. If say you did this half way along the length of a lymph vessel, the increased contraction rate here would close the one way valves more often against the flow from the extremity, restricting the flow rate here. You get an opposite effect, common in many complex fluid transport systems.
I think nature has largely taken care of this issue, as most DHT production happens at the bodies extremities in hair follicles and sebaceous glands. According to Merck hair follicles produce most of the DHT at around two thirds, with sebaceous glands accounting for the rest of the dermal production. So large hair follicles can produce more DHT, and i think this accounts for the enigma of MPB.
This is how i see it. At puberty the large scalp follicles start to produce a lot of DHT. This feeds into the lower lymph vessels of the head and face, increasing lymph drainage, reducing tissue pressures to allow larger follicles, you get beard growth. These larger beard follicles produce even more DHT feeding into the lower lymph system. The MPB area is right at the end of the lymph system, and the increased lymph vessel contractions lower down creates a restriction in drainage from the MPB area. In the individual this process is linked to other vascular factors i describe in my article. This scenario is consistent with the often lengthy time periods involved in the individuals development of MPB.
For a long time now i have been trying to generate interest from scientists who can, to test the lymphatic/ DHT effect as in the study linked above. It seems that as this is not in the interest of current lines of research, i just get a no comment.
This does raise an interesting test proposal that anyone taking Finasteride could try for themselves. This could significantly boost the effect of fin to grow more scalp hair. According to this the most powerful hair growth stimulant we have is DHT. In MPB it is just a case of too much in the wrong place, we need to make DHT work for us. Finasteride does significantly reduce overall DHT production, but for maximum effect DHT needs to be re-introduced were it matters. This is as a topical on the balding scalp.
There are DHT creams out there, so any volunteers?
Roger and Dr. Kemp,
If this technique shows a way to completely solve the inductivity problem why not just start using this technology to treat hair loss now? Why put time into searching for another way to solve the inductivity problem if this technology will do it now?
“Dr. Jahoda grew good quality hairs on his wife’s arm with DP cells alone.”
This isn’t quite correct. Jahoda created new hair follicles by implanting pieces of dermal sheath tissue into Reynold’s arm. He did this three times in total using a total of two different donors. In all three attempts, the DS tissue grew new hair follicles having dermal donor characteristics and epidermal host characteristics (note: the hair emerged from the skin in many different directions). Interestingly, DP cell implantation resulted in zero growth of new follicles.
Jahoda only needed to introduce dermal cells because he targeted the dermal-epidermal junction. This triggered the existing epidermal cells in the host to interact with the implanted dermal cells, thus forming complete follicles.
I’m guessing using implanted intact follicle pieces helped with placing the dermal cells at the exact location of the skin that triggers the dermal-epidermal interaction. The problem with using pure cultured dermal cells (absent of stromal tissue) is, it requires too many cells to trigger dermal-epidermal interactions due to cellular migration and injection inefficiency. Thus, most commercial injection techniques are aimed at stimulating existing follicles.
As you know, high passaged cells take on characteristics of lipid and bone cells, so it’s not currently possible to use cultured cells to restore a full head of hair using neogenic techniques. Dr. Kemp sought a way around this by creating “proto follicles” in vitro and then implanting them into the skin. This, limits the number of necessary passages required to restore a full head of hair.
Although his mice studies only resulted in 20% of the implanted proto hairs turning into fully mature hair-producing follicles, this represented a high percentage of success compared to injection techniques targeting neogenesis.
Personally, I’ve always thought this is an extremely promising area of research, and I hope Dr. Kemp is keen on continuing to develop it. Increasing the success rate does not seem all that difficult, as it’s simply a mechanical problem as opposed to a fundamental science problem. IOW, it was found that hair-shaft emergence depended upon implanting at the proper depth and orientation of the implant within the skin. Thus developing an advanced implantation device that aids with this placement would seem not-so-difficult of an obstacle to overcome. Then again, keep in mind, Dr. Kemp’s proto follicle studies were on mice. I’m not sure if this has ever been attempted in humans.
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Dr. Kemp:
Would the bank-preserved cells degrade at a slower rate than the remaining donor cells on the patient’s head? Or would the process of preservation instill a comparable amount of damage to the cells as leaving them within the host over a period of five, ten, or twenty years?
When you were at ICX, you received a grant for creating a stem cell bank. What is the status of this cell bank today?
Thank you,
jb
James. Although we haven’t confirmed it with human follicle cells yet, there is a large amount of information from a variety of sources to support the fact that cryopreserved cells can be stored for many years. It is the processes of cryopreservation and thawing that are critical and we will be optimising these before we provide the banking service. As to your other question, Intercytex sold the banked cells when it downsized several years ago.
Thanks for another interesting article. This technique utilises sheep cells which would create what is termed a xenograft and which would illicit a huge immune response in the patient so unfortunately it couldn’t be used
@Footy Your theory is interesting on a certain level, but I think you have some fundamental things about MPB, DHT and endocrinology wrong.
My understanding is, it’s not about where in the body DHT is made. DHT is in the systemic blood circulation, which means it’s made and circulating all throughout the body, and the local differences in effect are caused by the characteristics of androgen receptors in different local tissues. Some androgen receptors are highly sensitive to DHT, and others aren’t so sensitive, and the “geographical” distribution of where in the body differently functioning receptors are located is programmed by genetics, just like the color of your eyes and hair are programmed by genetics. In people with MPB, they have a genetically-programmed pattern of highly DHT-sensitive androgen receptors located in a certain pattern at the front and top of the scalp.
Also, you draw a distinction between trying to rejuvenate or regrow miniaturized follicles from injecting dissociated cells, and implanting follicles in hair transplantation. You say the former approach won’t work because of increased hydraulic back-pressure due to an impaired scalp lymphatic system in people with MPB, which restrains the growth of the nascent engineered follicles. While on the other hand, hair transplants are successful because the follicles are transplanted whole, and don’t have to push against this extra pressure during growth. Fair enough up to that point.
But, how do the transplanted follicles then survive in the long-term? We know they do survive and continue to grow, and even cycle, even though they’re supposedly sitting in the midst of a high-pressure lymphatic environment, which, according to you, restrains and shrinks native follicles. Which seems to dispel your theory. Transplanted follicles are able to survive this alleged high-pressure environment for many years, while native follicles in the exact same place didn’t.
James, if it was dermal sheath cells that Jahoda successfully used to grow hair doesn’t that bode well for Replicel/Shiseido since they’re using dermal sheath cells?
And IF Jahoda was able to make the DS cells work because he implanted them at the exact right depth then Replicel/Shiseido can simply implant the DSCs at that same depth and then Replicel’s treatment should also work the same as Jahoda’s treatment worked, right?
I understand that DP cells lose inductivity in mass pass culture but I don’t know if that’s the case for DSCs. Do DSCs have the same inductivity issues that DP cells do?
The dermal sheath cells that Dr Jahoda used were not passaged at all; I understand they were transplanted straight from him to his wife. So there would have been no loss of inductivity.
The dermal sheath contains progenitor cells that maintain and regenerate the dermal papilla. Interestingly, DS cells can migrate in and out of the follicle such that injecting them into proximity can result in uptake of the cells into the follicle. This is a completely different technique than targeting the dermal-epidermal junction in the skin. The former method rejuvenates existing follicles, and the latter creates brand new follicles.
That said, Replicel has a promising technique. However, DS cells also lose their inductive potential when expanded in culture. Also, the delivery method used by Replicel is not extremely efficient, so their technique most likely has the same limitations the rest of the world is working to overcome. Saying Replicel might have a marketable treatment in a couple of years is quite different than saying it will have an effective cosmetic cure (I.E. restore Brad Pitt hair on a NW 7 using a small number of hair follicles from the donor). While an interim treatment is possible, getting Brad Pitt hair will remain a dream for some time. I’m keeping in mind, given a large number of donor follicles available (I.E. not burned up by HT), it might be possible to (very expensively) continue to administer ongoing Replicel treatments and restore a lot of hair. Of course, patients would respond at different rates with some not responding at all. Also, Replicel could turn out to be a complete bust and end up as the next Aderans and ICX.
This speaks to the importance of Dr. Kemp’s ongoing research. It appears his organization will attempt to solve the culture expansion riddle in the laboratory prior to injecting real patients. His approach will initially be scientific in that he will work to optimize cellular expansion by observing the genetic changes to cells when using various precursor combinations. Thus, many experiments can be done much more cheaply than running trials and injecting cells into scalps using a wait-and-see approach and being locked into a specific protocol for the duration of the study.
Of course, all players in the game will attempt to figure out the cellular expansion problem, the delivery problem, etc. So that brings up the importance of funding this ongoing research. Replicel will try to get this cash from licensing its multiple product streams hoping that one hits (BTW, it stock price is currently going wild). Dr. Kemp proposes a different funding route. The main difference, if I understand it correctly is, a lot of world-class experts will be affiliated with Dr. Kemp’s organization, so we will see a broad-base of commitment to resolving ongoing problems. I expect this is a long-term commitment strategy to overcoming an extremely difficult set of problems.
So while we might see an effective interim treatment from Replicel, the real work still needs to be done in order to give every balding person a Brad Pitt head of hair. Having multiple approaches can only be seen as a good thing, and having an organization that centralizes the commitment from a very broad-base of players is a welcome addition.
As to whether Replicel should alter its protocol in order to try to figure out how to target the dermal-epidermal junction, this is a lot easier said than done. Aderans expended a lot of effort in this area, and I don’t think they were able to come up with a good solution. However, the approach was interesting. Using a 3-d matrix allowed the cells to clump, thus helping them to retain their inductive abilities. I imagine it also provided an implantation advantage, similar to Jahoda’s technique where matrix pieces could be implanted into slits into the skin. I don’t really recall the specifics of their research, but I recall Tom Barrows was working in this area early on and not much ultimately resulted from these efforts.
Although we’ve had much exciting news from companies that appear to be “on the verge” of solving the problem, so far, all it is is news. A marketable treatment has not yet materialized, yet alone a cure. Much work remains to be done.
I believe you’re correct. But if I recall properly, they were soaked in culture medium prior to implantation.
If as I suggest DHT does increase lymphatic pumping, it is important that DHT be largely produced at the ends of the lymphatic “pipework”. This is for the reasons of fluid dynamics I talked about in my post.
I am posting below about the issue of evidence for direct or indirect actions of androgens upon hair follicles in-vivo. We should remember in-vivo is where it matters.
On the issue of transplantation, people forget that in the early studies the authors accepted that there were two possible explanations. The alternative being a factor induced by the procedure itself. I think the historic evidence, what there is, supports this explanation. I elaborate on this in my article.
In modern tissue engineering, because of the spatial growth controls scientists have developed scaffolds to allow and direct tissue growth in-vivo. When you transplant large hair follicles, the healing creates a fibrose scaffold around these. It is this permanent scaffold that allows the hair cycle to continue to produce a large follicle against the external pressure. I describe the evidence for this in my article.
Getting back on topic here, and the viability of cell based treatments for hair loss. When hair follicles enlarge within the dermal tissue, they are subject to the recognised in-vivo spatial growth controls, like any other normal tissue growth. This also includes any kind of cell implantation intended to grow into large hair follicles in the MPB scalp.
Based on the idea that hair follicles react to androgens directly and differently, in over twenty years of such cell based treatment research, none of the various companies involved have produced any meaningful hair growth in the conditions of the MPB area. I think the scientists in hair loss research and the funders of this research, should reconsider the scientific evidence here.
I can see no hard evidence that androgens have any “significant in-vivo” direct effect upon hair follicle size. In fact the only in-vivo study in which Human MPB follicles significantly re-enlarged, clearly refutes the notion of any significant direct action of androgens upon follicle miniaturisation.
http://www.jaad.org/article/S0190-9622(02)61499-9/pdf
According to the direct action idea and the sensitivity aspect of this, there were more than enough androgens present to directly maintain the “susceptible” MPB follicles in the miniaturised state. In reality they enlarged by 400%.
There is far more evidence that the significant “in-vivo” effect of androgens upon hair growth is indirect, and the mechanism involved is fundamental to the evolution of hair growth.
I think it is time that scientists and funders, reconsidered the whole modern body of evidence when deciding upon valid research strategies for hair loss treatments.
James I have some questions about this paragraph:
“DS cells can migrate in and out of the follicle such that injecting them into proximity can result in uptake of the cells into the follicle. This is a completely different technique than targeting the dermal-epidermal junction in the skin. The former method rejuvenates existing follicles, and the latter creates brand new follicles.”
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It sounds if you’re saying that Jahoda accidentally happened to hit the exact right spot when he injected DSCs into his wife’s arm 3 times. What would be the odds of him hitting the exact right spot for 3 separate injections even though he wasn’t aiming for an exact right spot since he didn’t know there was an exact right spot at that point in time.
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Also, I’m not aware it was ever proved that merely hitting close to follicles with DSCs would cause the DSCs to migrate into follicles. Could you please post a link to a study that demonstrates that. If this is true then this is good for people like me who still have all of their follicles.
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Also, I have not read anywhere, not even 1 study, that says DSCs lose inductivity in mass pass culture so will you please provide a link to a study proving that as well.
jarjarbinx:
It’s not my intention to redirect this thread. Dr. Kemp is one of the premier researchers in the world, and I believe the focus of this discussion should be on his work and his intentions. I know absolutely nothing about hair research. He knows absolutely everything. His offer to answer our questions is a great honor and a tremendous opportunity to increase our knowledge.
That said, to briefly answer your questions to me:
- In the Reynolds experiment, Jahoda did not inject DSC cells. He implanted pieces of DS into purposefully-built cuts in the skin; thus targeting the dermal-epidernal junction.
2, 3. In answer to your other questions, please read the following paper: Replicel Publications
and etc
WO2005059119A2 - Differentiated cells - Google Patents
Thanks,
jb
Thanks. I’ll go through the material you posted tomorrow. And yes, we should keep this thread focused solely on issues about HairClone.
Here’s the problem I see with banking cells with a separate company. I’ve seen too many examples of companies refusing to use “x” that you got somewhere else because of [insert baloney reason]. Now, you know the reason is baloney and the company rep you’re talking to knows it’s baloney, but any attempt to explain the baloney-ness of it all is defeated with an apologetic, “Sorry, that’s just our policy.” So, I won’t be banking cells. I suppose guys that have plenty of cells to bank have little to lose except money. But, I’m a few HTs down the road and am very careful about my donor area.
At this time, I agree with you. I see no reason to bank cells with HairClone unless HairClone has a breathrough treatment to offer me at the same time. If I’m going to end up getting my hair back from Tsuji or Replicel then I’m sure they will bank cells for me. And HairClone can’t guarantee me that if I end up using Tsuji or Replicel to treat my hair loss either of them will be OK with working with HairClone to use my cells stored by HairClone. Replicel or Tsuji could posit that since the cells were not under total control of Replicel or Tsuji they do not want responsibility for whether or not the cells are viable.
The intention of starting the hair banking now is that we would use all the revenues from this to help fund acceleration of the development of the treatment. These patients by banking early would be first in line for treatment when it was available and we would be keeping them closely informed of our progress. As I mentioned before, we would also recognise the assistance that this group of people had given to development of the treatment by providing them a significant discount to the eventual treatment cost. We are attempting with HairClone to create a new concept in how treatments are developed, bringing together a very exclusive group of clinicians scientists and patents who will co-operate to greatly reduce the time taken bring the treatment to the clinic. From the outset, through various channels including this one, we have tried to be very open and pragmatic about our aims. We will certainly not introduce policies that would restrict patients and also, before we can begin this banking process we will need to obtain a license from the UK’s Human Tissue Authority. Before they will grant us such a license, we will definitely need to prove to them that we are in full control of the system and that the cryopreservation and storage does not affect cell viability and we are currently working hard to develop the required data.