lets vote who thinks replicel will be available in 2018 and why?

[TJT]

That's a great breakdown of the situation Swooping!

......Aside from this there is also the possibility of new hair follicle formation by DSC cells but they clearly mentioned that this is not their purpose but may be researched in a later stage. All in all I guess it will be very interesting to see what Replicel can bring to the table. The potential is there really but there are uncertainties too I guess. Let's hope for the best .

On the follicle neogenesis end of things, I am hoping that the Shiseido scientists including Ohyama and Tsuji have already figured it out, or are very close. The Shiseido video did show a mouse with human hair growing out of its head, and even though it's not quite the same as balding human scalp, it's very encouraging to see. As far as I know, Shiseido intended to combine Replicel's technology with their own, so let's hope they have it all figured out or almost there!

[Swooping]

Jup, I agree TJT. I guess it all depends on many factors on what Repicel will bring to the table. Some points that would be important in my opinion;

(DP = Dermal papilla, DSC= Dermal sheath cup)

-Did they actually succeed in properly culturing DSC cells without losing their signature?

There have been attempts to culture DP cells too. However currently nobody has succeeded in that without the DP cells losing their signature. Does this problem occur with DSC cells too? And if it does, has it been fixed? We don’t need “retarded” cells we need proper cells.

-How will the DSC behave when injected in the scalp?

I think this is an important aspect too. How will these cells actually migrate into a hair follicle? A hair follicle is encompassed by a connective tissue sheath. Will these cells actually be able to actually find their way in the niche they belong too? Will there be room for them? There must be at least some form of very precise delivery I would assume. So will they be able to find their way and accepted in the place where we want them to be? Experiments in rodents showed that cells derived from the DP or dermal sheath migrate and incorporate into existing hair follicles. As shown by these studies apparently the most efficient way of this to happen is during early anagen phase when cells are normally recruited to the DP. Will this happen in humans too? Also will it actually happen in a arrested miniaturized hair follicle? Therefore at this point we can’t say that if it will work for maintenance it will work just as well for regrowth. It seems logical but no, perhaps these cells will only be able to incorporate in a healthy hair follicle or one that is declining not a fully arrested one. Studies talk about this too.

-Do DSC really repopulate the dermal papilla?

Ok so this one is interesting also imo and requires a bit more explanation. The reduction of the size in a hair follicle with progressive hair thinning and loss includes a fail to maintain DP cell number. Recent observations have shown that this arises from a primary defect in the DP (in AGA). So indeed modulation of DP cell number seems crucial but are DSC cells actually responsible for re-populating the DP ? Do we really know for sure at this point?

As you can see in the illustration beneath (fig 4.) we don’t seem to know where these fresh DP cells come from. However a recent study (1) does seem to point out that some hair follicle dermal stem cells might be responsible for this and that these self-renewing stem cells reside in the dermal cup (in mice). However we need more studies to explain how everything works and to be exactly sure from where these fresh DP cells come from.






......Aside from this there is also the possibility of new hair follicle formation by DSC cells but they clearly mentioned that this is not their purpose but may be researched in a later stage. All in all I guess it will be very interesting to see what Replicel can bring to the table. The potential is there really but there are uncertainties too I guess. Let's hope for the best .

(1) http://www.cell.com/developmental-ce...807(14)00688-1

[Renee]

Thank you lacazette. There is a lot of research on their on dsc cells if cultured correctly they will give rise to new hair. Hence if it works as maintenance it should also induce new hair. Members like calex just write without doing research!

[lacazette]

From the US army researchers in 2014 who recently patented the HF neogenesis on skin graft:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057739/

"A landmark observation in human hair follicle neogenesis was made when Reynolds and colleagues transplanted male DS cells from the scalp into the forearm of a female human subject. This experiment demonstrated that hair growth was partially dependent on DS cells for formation of a DP [104]. Recently, fibroblast cells isolated from the peri-bulbar DS have also been shown to induce hair follicles [105]. These studies demonstrate that only dermal fibroblasts from specific locations in the skin have the capacity to induce hair neogenesis.

The clinical development of hair follicle inducing dermal cells as a cellular therapy for treating alopecia is being pursued by Replicel Life Sciences Incorporated (Vancouver, BC, Canada) [117]. Replicel, is conducting a clinical trial (clinicaltrials.gov identifier: NCT01286649) using the autologous cultured dermal sheath cup cells isolated from a biopsy from the occipital scalp for the treatment of androgenetic alopecia in humans. Dermal sheath cup cells are located in the peribulbar region of hair follicles (Figure 3) and have lower alkaline phosphatase activity than DP cells. Dermal sheath cup cells appear to be similar to DP cells in their hair inducing capacity [105].


Practical challenges including scale up, formulation, storage, transport and delivery mechanisms are the main challenges to development and clinical translation of preclinical observations.

if Shiseido use ameliorations in their protocol regarding those challenges compared to phase1, ( and there was a lot of progress in each of them), then DS cells will keep the power to induce HF neogenesis, and not only help the existing ones

[Renee]

^^^^^^Makes zero sense^^^^^^

Being able to halt further loss does not effect regrowth. Hopefully increased dosing is able to increase regrowth though. fingers crossed toes crossed bellybutton crossed!.

If this perma halts and creates immunity to future loss it is a cure* Just not if you have already lost hair to a point you are unhappy with. But for any 17yr old guy just starting to be like wtf! im at the very early stages of temporal thinning or recession it is a CURE* for all intents and purposes.

hope this pans out even if its maximum effect is the ability to future proof people against loss. I bet the constant fear "where am i headed" nw2 3 etc would greatly decrease. It would also open up options later stage guys to go for larger ht sessions if they so desired.

Good lord I remember in 2008 follica was going to be the cure

Go read about dermal sheath cup cells before you write.

[CAlex]

^^^^^^Makes zero sense^^^^^^

Being able to halt further loss does not effect regrowth. Hopefully increased dosing is able to increase regrowth though. fingers crossed toes crossed bellybutton crossed!.

If this perma halts and creates immunity to future loss it is a cure* Just not if you have already lost hair to a point you are unhappy with. But for any 17yr old guy just starting to be like wtf! im at the very early stages of temporal thinning or recession it is a CURE* for all intents and purposes.

hope this pans out even if its maximum effect is the ability to future proof people against loss. I bet the constant fear "where am i headed" nw2 3 etc would greatly decrease. It would also open up options later stage guys to go for larger ht sessions if they so desired.

Good lord I remember in 2008 follica was going to be the cure

[Renee]

If it works to maintain what you have then it should work to regrow your hair.

[dutchguyhanging]

Yup Swooping said it well. If they prove it as a good maintenance treatment it would still be very valuable, especially for those in early stages of hairloss.
Besides if this does stop hair loss effectively, then hair transplants seem a much favorable option for those above NW5.

i told many times here but doesnt hurt to say it one more time. In quantum mechanics there is no such thing as "stopping hair loss".
you cant just stop the behaviour of matter and its interactions with energy. It can go 2 ways either improvement or loss.
Fin or minox is just stealing time or slowing the rate of hairloss. For some fin users hairloss speed is at bare minimum means you dont feel it cosmetically.
If replicel results would be like fin, then i m sure it wont work for everyone and at the end people here would still shout for the cure. And yes once you are NW3, you will eventually be Nw5 or above. So you cant just maintain it forever...

again i am repeating, you CAN NOT STOP hairloss. you

[TJT]

Indeed, they didn't exactly classify it as a "maintenance solution". However the way how they present everything it seems they are aiming for a treatment that is mainly preventative with some improvement imo.

I'm glad that you're acknowledging "IMO", because these are indeed just your assumptions, which may or may not be correct. At high dosage and with repeat injections (maybe ten instead of two), there may be full regrowth. We will not know until they try, and you're right, it's extremely important that they trial for the long 39 months. If the second injection improves on the results of the first, then the results are cumulative. They wouldn't claim that it will bring all hair back at this time because they don't have the data to support that right now.

Also they are going to test on people with thinning hair and not extensively bald people. I find that vague. I mean someone who is NW3 is basically extensively bald in his temple areas. His goal would be to fill up that area with hair, because it's completely devoid of hair. A NW6 would have the same goals but in a NW6 pattern. With thinning hair in my opinion they are more directing to some hair follicles that can somewhat be "saved" to name it like that.

I agree it's ambiguous. Is a CLASSIC Norwood 3 "thinning hair"? Not really, it's thick hair and some bald scalp. In the classic Norwood progression the hairs at the hairline go from thick to gone very quickly as the hairline advances. The term "thinning hair" implies diffuse thinning. If their treatment works best on thinning but present hair, then it would work best on diffuse thinners. For instance it may bring a NW6 diffuse thinner back to NW1, while having no effect on a classic NW3 with good density. Just some interesting possibilities, but of course it's all a guessing game at this point.

[Sogeking]

Yup Swooping said it well. If they prove it as a good maintenance treatment it would still be very valuable, especially for those in early stages of hairloss.
Besides if this does stop hair loss effectively, then hair transplants seem a much favorable option for those above NW5.

[Swooping]

What is a maintenance treatment actually? We classify finasteride as a maintenance treatment. Yet it does improve hair counts in many people. In my opinion we can classify something as a maintenance treatment if it will actually keep you at least at (or above) baseline levels for a long time. Finasteride does this in the overwhelming majority of people (5+ years).

Indeed, they didn't exactly classify it as a "maintenance solution". However the way how they present everything it seems they are aiming for a treatment that is mainly preventative with some improvement imo. Basically just like finasteride. Let's not downplay the significance of such a cell based treatment. A young kid could just get some injections and be done for a few years or maybe permanently. That is highly convenient and side effect free. Would be absolutely huge. The market value would be insane too. Treatments like cb-03-01 and setipiprant wouldn't stand a chance. Finasteride would be history.

Now why do they go with a lengthy trial of 39 months? Seems obvious to me. To actually establish if it can act as a "maintenance" treatment. To actually establish if the injections can provide stability to stay above baseline levels for a longer period of time. This is where their primary hypothese is based on anyway. Repopulate the DP niche with androgen insensitive cells by injecting DSC. It will also give them enough time to play with dosage and frequency of injections and such. And it's crucial I repeat crucial to undertake a lengthy trial to establish this. A 1 year trial won't tell you much about this. Minoxidil would keep you above baseline for 1 year too however we know that not a long time after you will probably go under baseline and continue balding. A 104 week open study was actually done recently about this; http://www.ncbi.nlm.nih.gov/pubmed/26387973

RESULTS: In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104

You all get the point. Also they are going to test on people with thinning hair and not extensively bald people. I find that vague. I mean someone who is NW3 is basically extensively bald in his temple areas. His goal would be to fill up that area with hair, because it's completely devoid of hair. A NW6 would have the same goals but in a NW6 pattern. With thinning hair in my opinion they are more directing to some hair follicles that can somewhat be "saved" to name it like that. Just like finasteride can do.

Androgen sensitive cells. Androgen sensitive cells will be present in the resident hair follicles of people suffering from AGA. However, the DSC cells injected are derived from follicles at the back of the scalp that are androgen insensitive. The objective is to introduce enough DSC cells to the follicle that the properties of the injected cells are dominant. Over time, as the resident androgen sensitive hair follicle cells become senescent/die off, we anticipate the DSC cells will become progressively more dominant. Recent evidence indicates that a subset of cells in the cup region are responsible for repopulating other HF cells including DP (Rahmani et al. Developmental Cell. 2014 Dec; 31: 543-58). In theory, the injected ‘androgen insensitive’ DSC cells can repopulate DS and DP with ‘androgen insensitive’ cells.

Due to the methodology employed using our injector device, and because we will be injecting people with thinning hair and not extensively bald people, it is simple migration of cells to resident follicles and their subsequent enlargement which is expected.

Participants will remain in the trial for approximately 39 months.

It's all speculation though, indeed. We can only wait till the end results. Their phase 1 is absolute sh*t obviously and says nothing besides the fact that it's very bad. Let's hope for the better. And due to the above reasons it's smart of them to undertake such a lengthy trial which is a good thing.

[TJT]

That's not what I got from it, they averaged a maintained 14% growth in 70% of the people in the trial(a very small safety trial, with very small dosage) It's a functional cure so far in that at a low dose people maintain unlike Rogaine which fades.

If they can raise the dose(inject more cells), theoretically they can give a higher regrowth and complete maintanence.

To me it sounds like they ideally want it to be a replacement for Hair transplants, instead of transplanting follicles, they transplant cells in hopes that those cells all bind and grow.

Very interesting product to watch and at the very least Shisedo is starting within the next few weeks so we should get an update sometime next year.

Yes, the video said nothing of it only being a "maintenance" solution or anything like that, and in fact even the low dosage proved that it increased (not only maintained) density, and that was only a safety trial. It's a functional cure (it doesn't eliminate the base mechanism of pattern baldness, but functionally cures it since the new follicles don't succumb to the mechanism).
Essentially he said absolutely nothing new or different that Replicel hasn't already said in the past. Also, note how he says "we think"; he doesn't know - nobody knows because Phase 2 hasn't started and completed. David Hall said the same thing in this interview: http://www.midasletter.com/2014/10/r...rview-podcast/. With increased dosage and repeat injections, it could be a full functional cure that increases density to original, or may not improve on the Phase 1 results (doubtful). It all depends on the percentage of follicles that the treatment can render androgen-insensitive, which nobody knows at this point. Anything else at this point is speculation and guys with a less-than-complete grasp of English (no offense) drawing their own conclusions from the interviews and presentations they see.

[cratusg]

I kinda agree Baldybald why would anybody go thru a procedure like that that would have the same effect as a pill or topical? especially if its going to cost the same as a transplant but with zero growth. When i looked at it before it sounded like it creates regrowth but not so much at the moment, perhaps Shiseido have got further then Replicel

Yeah but replicel might be 1 or 2 injections and Seti is for a lifetime. Lazy people would rather take the easy way.

[HelloVera]

I kinda agree Baldybald why would anybody go thru a procedure like that that would have the same effect as a pill or topical? especially if its going to cost the same as a transplant but with zero growth. When i looked at it before it sounded like it creates regrowth but not so much at the moment, perhaps Shiseido have got further then Replicel

[baldybald]

Now if it is only for maintaining, replicel will not last for long. The reason is that setipiprant may come to the market and of course everyone will choose pill instead of replicel because it is easier and that is why if replicel will only maintain without re growth then it is not a smart thing to launch