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  1. #11
    Senior Member Desmond84's Avatar
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    Quote Originally Posted by walrus View Post
    Desmond, it seems that you are slightly playing down the recent achievement of Christiano and Jahoda at the beginning of this thread. Now that they have established proof of concept in humans (perhaps the most difficult step) - a base to work from - there is no reason that the figure of 22% gene expression can't be increased through further experimental refinement.
    Brother, I'm not playing it down. I wanna make sure their work continues! I want to see more ppl joining their team trying to improve this technique...This is the entire point of this thread...incremental improvement to this technique.

    They've gone full throttle and made everyone aware of their research! My mum even watched it and told me about, which was very surprising to say the least!

    But, I don't want to wait another 10 years for someone to come along and say "hey I think we can improve this"....I want the research to start now, because we all know how long it takes for new treatments to go through trials!

    This thread is simply there to gather data about what might be the reason DP cells are such a pain to culture! and ways we can come up with to help Jahoda & Christiano to continue!

  2. #12
    Senior Member Desmond84's Avatar
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    We must be objective in analysing data and understand what was still missing so we can improve on it!

    As much as I love Tsuji's work, I have to admit all their technologies will be useless until DP cells are fully cultured...it's a fact.

    And once we know the problems, we can move in the direction of solving them objectively...

    We used to think 2014 was the year of Aderans. 2015 was Histogen. 2016 Replicel and cure will be here by 2020. But we were wrong! Some may say way off!

    We need our younger generation of baldies to enrol in Biotechnology courses and show more enthusiasm towards developmental biology.

    We need to work the problem from the grounds up. We need a large pool of researchers at our disposal before we discuss the funding issues. Right now, we have a handful of decent hair researchers...period.

    I want ppl to read this thread and understand, Jahoda needs a new generation of bioengineers to help him with new ideas...

    I want us to find the cure

    - Des

  3. #13
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    Quote Originally Posted by Desmond84 View Post
    Brother, I'm not playing it down. I wanna make sure their work continues! I want to see more ppl joining their team trying to improve this technique...This is the entire point of this thread...incremental improvement to this technique.

    They've gone full throttle and made everyone aware of their research! My mum even watched it and told me about, which was very surprising to say the least!

    But, I don't want to wait another 10 years for someone to come along and say "hey I think we can improve this"....I want the research to start now, because we all know how long it takes for new treatments to go through trials!

    This thread is simply there to gather data about what might be the reason DP cells are such a pain to culture! and ways we can come up with to help Jahoda & Christiano to continue!
    I agree that it can be frustrating to watch research progress at a snails pace.

    Also, it's a shame that the full text of the paper is behind a pay-wall. I'm sure a lot of people outside of academic institutions with access would like to read it.

  4. #14
    Senior Member Desmond84's Avatar
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    Quote Originally Posted by walrus View Post
    I agree that it can be frustrating to watch research progress at a snails pace.

    Also, it's a shame that the full text of the paper is behind a pay-wall. I'm sure a lot of people outside of academic institutions with access would like to read it.
    True. Well let's use this thread as a way to help ppl access some of the information in these research papers. Here's the important segments of Jahoda/Christiano study for you to read

    "Spheroids formed readily by 24 h and were morphologically akin to intact dermal papilla (22). Per experiment, between 10 and 15 spheres were placed between separated foreskin epidermis and dermis, which was recombined and grafted onto SCID mice. Strikingly, after 6 wk, we observed de novo hair follicles (Fig. 3C) from five of the seven donors (Table S3, Fig. S2), which we confirmed were comprised of human cells using an antibody specific to human nuclei (Fig. 3D). On two occasions, unpigmented hair shafts were observed emerging from the skin that had been implanted with spheroids (Fig. 3E). Sebaceous glands were not seen in follicles created after spheroid transplantation whereas these glands were detected in follicles induced by transplanted intact dermal papillae."

    "We were also able to visualize mouse blood-vessel formation, particularly around de novo follicles, indicating anastomosis with the graft"

    "The longest duration of any graft in our study was 6 wk, and therefore long-term follicle function was not assessed. At this endpoint, the efficiency of inductivity varied between donors, ranging from 10% to 60%."

    "Three-Dimensional Culture Partially Restores the Intact Dermal Papilla Signature. The average correlation coefficient between intact dermal papilla and cells at p3 was 0.42 (range: 0.39–0.44) whereas between intact papillae and spheroids it was 0.56 (range, 0.55–0.58)"

    "The observation of hair follicles within grafts, as described above, suggests that the 22% restoration of papilla signature is sufficient for follicle neogenesis. However, as complete hair-follicle morphogenesis involves epithelial:mesenchymal interactions, it is likely that external paracrine signals will be required for full signature restoration and development of external hairs. Importantly, in this study, we have demonstrated that dermal spheroids are, by themselves, capable of initiating the hair induction process in non-hair-bearing human skin, where there are no previous epidermal “hair-follicle” signals."

  5. #15
    Senior Member Desmond84's Avatar
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    So the last paragraph highlights two points:

    1) We need to improve on this technique to achieve better DP signatures (above 22%)

    2) We need to carry out more study to figure out the necessary signals and growth factors for the mesenchymal:epithelial interaction to achieve follicular neogenesis.

  6. #16
    Senior Member Arashi's Avatar
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    Hi Desmond,

    The thing I don't understand about all this: why does Tsuji lab need to culture DP cells ? The goal is to create epithelial and mesenchymal (derma papilla) cells from iPS cells right ? It's a different approach than Jahoda's (who is just culturing DP cells).

    Thanks to recent findings, iPS cells now can be easily, quickly and safely expanded (though officially that's ofcourse yet to be proven with the currently running clinical trial). The challenge however that Tsuji is facing is getting those iPS cells to differentiate into epithelial and mesenchymal cells. What I understood from their research (but correct me if I'm wrong), is that once they've done THAT, then they're done, since the hair they created DID contain the right pigmentation etc.

  7. #17
    Senior Member Arashi's Avatar
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    Hmmm to answer my own question, I think Tsuji labs is looking at both possibilities, right ? I see they're talking about culturing the Epithelial and DP cells, but they're also talking about using investigating the use of iPS cells...

  8. #18
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    Okay guys I am obviously lacking in terms of knowledge of hair follicle parts, biological interactions and so on.
    However Des, I agree with you. The recent findings of Jahoda and Dr. Cristiano told us how far they still are.

    So I have some questions. Basically how do spheroids make the DP cells multiply? You take DP cells, from the base of the hair, you insert them into this spherical culture, but what are the so called growth factors? AS fr the lack of the sebaceous glands, I thought that arrector pilli muscle serves the purpose of making the hair follicles "stand up", although sebaceous glands make the hair oily so it wouldn't become too brittle.


    Also I came across this article published in 2009.:

    http://www.ncbi.nlm.nih.gov/pubmed/19238412
    Inhibition of glycogen synthase kinase-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1 in human primary dermal papilla cell culture and maintains mouse hair bulbs in organ culture.

    It mentions the importance of FGF-2 as well. Although Cotsarelis's study says FGF-9 is used when forming hair follicles. So why not fgf-9 with dp cells when the spheroids are implanted in the skin.



    Okay more subquestions. Which compounds or proteins were used for gene expression?

  9. #19
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    Hey desmond have you seen James Bond's recent posts?

    could somebody maybe add them here?

  10. #20
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    The truth guys is that unless there's a miracle, we will barely have anything new in 2020. If things go somewhat well, we might have histogen by 2020 to grow some hair on those of us who will have any left.

    Replicel might pull it off but honestly they had very poor data as you all know.

    Follica who knows, but it looks like they will stay quiet for a while again now.

    All the rest including Jahoda and tsuji is a long time away

    I'm just glad I shaved in February and was able to accept my self. At least I wasn't thinking about hiding my thinning hair back then.

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