by Kevin Rands | September 27, 2016 5:54 pm
Organ Technologies and Riken have partnered with Kyocera to head up one of the most promising new hair regeneration projects[1] in the industry. If successful, it will enable the generation of large quantities of follicles from just a small cell extraction. You can read more about the project here[2]. We also encourage you to view the following YouTube video[3] for a very interesting overview of their work.
Interview Participants:
Thank you to all the HairLossTalk Forum[4] members who put together this outstanding list of questions.
Article Summary: Organ technologies is developing what many expect to be the most viable option for creating an unlimited supply of new hair follicles from hair loss sufferers own heads. They are targeting commercial availability of 2020. Their technique uses your own cells to harvest, multiply, and then inject into areas of the scalp which are losing hair. From there, it will grow on its own.
This technology very well may be implemented by skilled hair transplant surgeons in the future, who have already mastered the art of creating a natural appearance. But this will be different. Organ has announced in this interview that they’ve not only found ways to control the exact width and color of the resulting hairs, but they can also achieve incredible density, and control the direction of hair growth. This will be a massive improvement over current techniques which can only use your existing hairs – often very mature and thick, and therefore unnatural looking along the hairline.
Being able to populate the hairline with baby-fine, lighter hairs, without any scars from the donor area, and without limitation to the density in the recipient area will be a game change for the hair transplant industry, and hair loss sufferers.
Keiko: Question 1: Based on earlier information that was released, there were still some problems to overcome. The process related to culturing mesenchymal stem cells and epithelial stem cells was a critical issue that had not yet been resolved. Have you resolved this issue, and are there any previous roadblocks that have been resolved?
Mr. Toyoshima: Ok, I, Toyoshima [From the Research Team] will answer these questions. I’ve understood the challenge mentioned in this question as a challenge in clinical applications to human beings. Is this a correct understanding?
Keiko: Yes. That is correct.
Mr. Toyoshima: For applications of our technology, both mesenchymal stem cells and epithelial stem cells, which are applicable to human clinical applications, are needed. With respect to the development of the technology to cultivate mesenchymal stem cells, that is papilla cells, being applicable to human clinical trials, we are already in progress now for development. On the other hand, as for the technology to cultivate epithelial stem cells of follicles, it still remains a significant challenge globally. We are currently in the middle of research and development for this. Based on our recent research results, we finally have some prospects and expect this issue to be resolved in the near future.
Keiko: That is a huge step toward the clinical application, isn’t it?
Mr. Toyoshima: Yes, in terms of transitioning from basic research to clinical application, we are finally coming out of the basic research phase toward the clinical application phase.
Keiko: Thank you. Are there any other roadblocks preventing forward progress on this project?
Mr. Toyoshima: Well… at this point, the challenge which I’ve just mentioned is the biggest challenge we face. There are other challenges, but they are rather related to engineering, so in terms of a roadblock for the clinical applications, we believe our issue has been almost solved.
Keiko: Thank you. I believe we’ve already touched Question #2. As you said, the challenge relating to epithelial stem cells remains as the biggest challenge.
Mr. Toyoshima: Yes, as I mentioned earlier, we consider the development of the technology to culture epithelial stem cells as the most significant issue we face. In order to regenerate a clinically effective number of follicles, a sufficient number of cells need to be secured while satisfying the safety and functional requirements. These are tough challenges, so also pose major issues to us.
Keiko: Question 3: To what extent do you think that the newly created hair (follicles) will mimic the donor hair (follicles) in terms of gene expression and visual traits?
Mr. Toyoshima: For regeneration of hair, the most important thing is whether hair can be regenerated or not rather than gene expression. In this sense, we conducted animal testing to regenerate hair and analyzed its form, and the internal structures which characterize hair. Further, we analyzed hair growth cycles. Hair grows and falls in cycles and in certain intervals between growth and resting phases. So we conducted analysis on these patterns. These analyses indicated that the form, internal structure, and especially hair cycle of regenerated hair will typically match all those traits from the follicles where the cells were originally collected. These factors are the most critical factors in defining the length and width of hair. As we succeeded in regenerating all of these factors, we feel that we have succeeded in regenerating all the characteristics which largely contribute to formation of naturally growing hair. We have succeeded in regenerating hair similar to the original normal hair.
Keiko: This may be a very simplistic question, but some people were born with rather thick hair while other people with soft thin hair. There are many types of hair. So with your regeneration technology, are you saying that regenerated hair will have characteristics identical to the characteristics of the original hair even in situations like this?
Mr. Toyoshima: Yes, that is correct. For example, in the case of patients with male pattern alopecia, on the back of the head, they usually maintain the quality of hair which is similar to the quality they used to have when they were younger. So we believe that characteristic can be regenerated. If it is a thick hair, thick hair can be regenerated, and if thin hair, thin hair can be regenerated.
Keiko: Question 4: Thus far in your research, have you been able to attain an unlimited number of cells from a single biopsy? If not, what is the maximum number of total cells that can be amplified from the donor sample? How many new follicles would this typically result in?
Mr. Toyoshima: This is a great question. Generally speaking, it is said that there is a limit to stem cell proliferation. It is generally known that the stem cell function is lost with proliferation, therefore yes, there is limit to stem cell proliferation. In case of human follicular papilla cells having the function as the mesenchymal stem cells, the stems cells can be multiplied by several thousands of times in 3 weeks when we use our technologies. On the other hand, as for the epithelial stem cells, as I mentioned earlier we are still in research for this, therefore there is only a small number of human cases. Consequently, an accurate value for this case is yet to be determined in the near future. However, collectively from these researches, we think that we may be increase follicles at least by about 1,000 times.
Keiko: Question 5: Several users have scars from previous hair transplants. Both from strip excision and follicular unit extraction on the back of the head. There is also some damage to the skin tissue in the recipient areas towards, the front. One of our most popular questions was whether primordium hairs will be capable of growing through these and other types of scars (such as burn scars), and be capable of healthy growth in such an environment?
Mr. Toyoshima: We appreciate their interests in this and asking this question, and would like to offer our technologies to as many patients with scars as possible. Hair transplant procedures often leave some damage in the skin, forming scar tissues thus significantly deforming the subcutaneous tissues structure, or resulting in loss of the subcutaneous fat layer underneath the skin. However, follicles have a characteristic which enables them to grow through normal hair cycles by interacting with the surrounding tissue. As far as the effectivity on such skin with a serious damage, the effects of our hair follicle germ regeneration technology in such case is yet to be determined, therefore we believe that we still need to conduct significant verification for that purpose. However, it is not that I have only bad news. With our hair regeneration therapy using the hair follicle germ regeneration technology, we can artificially combine cellular tissues to tailor to the specific needs of the patient. Therefore, we believe in principle, that even for a patient with various special clinical requirements such as scars, we will be able provide a hair regeneration therapy for these individuals in the future, which is carefully tailored to such needs.
Keiko: Is this also true in case of the scars generated not by previous hair transplants but other types of scars such as burn scars?
Mr. Toyoshima: Yes, that is correct. And we believe that if we can accomplish this, we will be able to make an even bigger contribution to society. However, I have to say that once we begin making progress towards clinical testing, we’ll be better able to provide you with a clear response on whether this can really be done or not. At this point, please forgive us for this level of response.
Keiko: Sorry to press you on this, but what time range are we talking about, when you anticipate knowing more? Is it something 5 years or 10 years from now?
Mr. Toyoshima: Well… we first have to develop a technology to treat regular alopecia patents. As for other types of patients such as those with highly advanced alopecia, etc, we will consider a therapy after that.
Keiko: Ok, I understand that these cases with special requirements will be handled in subsequent phases. Question 6: Regarding the process of delivering the hair follicle primordiums to the scalp: Do you anticipate this being an automated process performed by a device, or will it require the hand of a trained and skilled surgeon, similar to hair transplants? As a follow up to this, have you seen success injecting the follicle primordium directly into the scalp with a needle, or must they be delivered to the skin with an incision?
Mr. Toyoshima: We believe that in order to provide our technologies to a broader range of people, we will eventually need to automate the process using a device. However, the current level of the skills owned by surgeons specialized in hair transplants is excellent, generating great results in treatments of alopecia patients. Therefore, we would like to leverage on such skills of surgeons as much as possible. Eventually, these skills are accumulated resulting in certain processes. Therefore, we believe that it is appropriate to develop automation devices incorporating such processes.
Keiko: Does this mean that such automation would not require a surgeon with special skills and would enable a regular clinic to provide your therapy?
Mr. Toyoshima: Well, of course, unfortunately considering potential cost of such devices, it might be difficult for any clinic to provide the therapy… however, we are aiming to have our therapy to be implemented in as simple as possible of an environment. As for the question about needles… Our transplanting technique was developed based on the FUT, Follicular Unit Transplantation, which is the surgical autografting used by hair transplant surgeons for hair loss treatment. The needle/surgical knife used for FUT is extremely small. The size of the surgical knife we used for our published research paper is almost same as that of a needle. Therefore, although we will do a skin incision, it will be a very small incision.
Keiko: Meaning it will not leave any scar?
Mr. Toyoshima: Yes, it will leave almost no scar… the scar will not visible at all. Yes, so the process requires a skin incision, but please understand that the incision will be about the same size as needle head.
Keiko: Thank you. Question 7: On the topic of aesthetics: Do you think the direction of hair growth be controlled by natural processes in the skin, or will the placement and positioning of the primordium cells by a qualified surgeon cells play a role? There was previous mention of using a “Nylon Thread Guide” for controlling hair-growth direction, and to limit epithelial cyst formation. Is this still the current plan?
Mr. Toyoshima: This hair-growth direction, which is the flow of hair, is determined when hair is generated. For our published paper, we create a small incision using a small surgical knife, which, as I mentioned earlier, is in the same direction as the hair flow. When the hair follicle germ is grafted in this incision, all hair was regenerated in the same direction as the original hair flow. On the other hand, as an experiment, we also created a small incision for grafting in the opposite direction. This was an experiment using body hair. It is known that the connection direction of arrector pili muscles of hair completely align with hair flow. The results determined that the connection direction of the arrector muscles of hair, as well hair flow, was actually influenced by the surrounding tissues.
Keiko: So this is what you mentioned earlier that transplanted follicles interact with the surrounding tissues…
Mr. Toyoshima: Yes, we believe this can happen. This is dependent on types of hair, the condition of skin for transplant, etc., therefore although we cannot say that it will definitely happen, we think that the direction of regenerated hair growth will align with that of the original hair. For this, we plan to develop a clinical model in the clinical research in the future in order to further study this point. As for the “Nylon Thread Guide”, the most important objective of using it is to prevent a formation of epithelial cyst. As far as the determination of hair growth, it is used to determine the direction of connection with epidermal direction. Transplanted hair follicle germ should not form a cyst, under the skin, therefore in order to prevent such case, we need to make sure that the epidermal layer is firmly attached to the epidermal layer of the transplanted regenerated hair follicle germ. Nylon thread guide is used to ensure this. Therefore, we will probably have to use it in clinical application, and its use is expected to prevent such abnormal results. So we think it is reasonable to use it.
Keiko: Thank you. Question 8: Certain individuals with advanced androgenetic alopecia experience significant miniaturization of follicles and extensive loss on the sides and back of the head. This is the typical location for donor follicles for transplants and with your therapy. As a result, these donor follicles may be extensively affected by AGA prior to the procedure. What can these people expect from your therapy?
Mr. Toyoshima: This question rather relates to the AGA clinical condition; therefore, I believe it would be more appropriate for a physician to talk about this. However, I can provide you with an answer from a biologist perspective. It is thought that the site of AGA onset is already determined in the stage wherein the follicular organ is generated, and follicular papilla cells store information such as destiny, determining the site of male pattern alopecia onset, to a certain degree. Consequently, follicles on the back of the head and those on the front of the head will have different destinies, and it is thought that patients with alopecia develop the disease in a specific site in this manner. As the disease gradually progresses, follicles on the back of the head and also those on the side of the head also become miniaturized. However, even though the disease has progressed into those areas, there is still a large number of normal follicles left. Based on this, we are currently conducting a human-tissue study using dermal tissues collected from the back of AGA patients’ heads in order to verify the possible number of normal follicles which can be collected from such areas, and whether cells collected from such areas have the function needed for follicular regeneration, etc. So far, we have found out that there is a large number of normal follicles on the back of AGA patients. We believe that collecting the cells from such areas will definitely result in regeneration of normal follicles.
Keiko: Question 9: Studies have shown that the hair shaft thickness seems to be determined by dermal papilla size. If this is true then could it be possible to also control hair shaft thickness with the hair primordium method?
Mr. Toyoshima: Based on past research, the size of the follicle (that is, the size of papilla cells… the cells used in developing regenerated hair follicle germ) was determined based on the type of hair from which it had been derived. To put it more technically: follicle size arises from a biological principle that organ size, its density, and the distribution pattern is determined by a theory called the reaction-diffusion system. So using this principle, when we changed regenerated hair follicle germ, we found that the number of regenerated hair per a regenerated hair follicle germ, varies according to the germ size. In other words, the number of regenerated follicles may be controlled based on the size of the hair follicle germ, and type of papilla cells. It is thought that the size can be controlled to a certain degree by changing the type of follicles where the papilla cells are derived from.
Keiko: Thank you. Question 10: Suggestion from a user regarding # 8 – Some feel that hair transplants are detectable because natural hair lines do not usually have extremely thick follicles in the front. Natural hairlines usually include miniaturized follicles and “peach fuzz”. If you could control hair shaft thickness to varying percentages, would you be able to implant intentionally thinner hairs near the front and achieve a more natural appearance?
Mr. Toyoshima: This is related to one of the earlier questions. A hair follicle germ that is regenerated intentionally small, will result in a small follicle. As pointed out in the question, therefore, just as done in existing FUT therapy, our technology enables us to regenerate miniaturized follicles with 1-hair in the front, while regenerating thick follicles with 2- or 3-hair toward the back of the head. Therefore, we believe, we can eventually attain a more excellent result compared to the result generated by existing FUT.
Keiko: Question 11: The primary advantages of the hair follicle primordium method are well known: (1) A less invasive procedure than hair transplants, and (2) Access to a higher number of hair follicles. Current methods also fail to deliver density that matches a natural head of hair. What other advantages are you anticipating for the hair follicle primordium method in comparison with current methods? For instance, do you expect to be able to archive a higher density or the ability to control hair color?
Mr. Toyoshima: As you pointed out, our technologies enable us to control the density as well as hair color. Based on the results we’ve obtained, when cells used to regenerate hair follicle germ have no melanocyte stem cells, the regenerated hair will have no color. On the other hand, we can mix a cell population, which has been collected from follicles having melanocyte stem cells, to the cells used to regenerate follicular primordium. One follicular primordium is usually composed of 10,000 units of epithelial stem cells and mesenchymal stem cells. So mixing only 200 cells containing melanocyte stem cells will produce hair with color. Therefore, we can control the color of hair by adding a small number of melanocyte stem cells. We can change the size of regenerated follicular primordium or control the density in grafting. Therefore, based on the results we have, it is said that in case of a human being, there are about 60 to 120 hairs growing in an area of 1cm2… and we can easily control that with our technologies.
Keiko: Question 12: From your research, how long does it take for a primordium to grow into a fully functional hair follicle after being delivered to the scalp?
Mr. Toyoshima: To answer this question… we have completed only a small number of clinical cases until now, therefore it is still difficult for us to provide you with specific time period. However, while the current FUT therapy generally requires 3 to 6 months before attaining the expected result, the results of our limited cases have indicated that our technology will also attain the expected result in a similar period of time.
Keiko: Question 13 was removed due to translation difficulties. Question 14: Previous estimates targeted the availability of the technology to be in “practical use” by 2020. Does practical use mean commercial availability to the general public? If so, does this mean that human trials would need to begin a year or two before 2020?
Mr. Sugimura: Yes, as you pointed out, although with an assumption that there is no specific problems, when we say “putting the technologies into use”, we mean “starting to offer it to the general public as a treatment not covered by health insurance”.
Relating to Question #15, we first plan to put the technologies into use in Japan, therefore we need to go through a certain set of procedures as the preliminary steps, in accordance with the “New Act on Regenerative Medicine”, and obtain a regulatory notification on our technology as a Class 2 Regenerative Medicine. The clinical study starts only after we receive that notification. Therefore we are thinking to start a small-scale clinical study to evaluate its safety and effectiveness in 2018.
Keiko: You have already touched on this, but in terms of offering this therapy to people around the world, will a separate regulatory approval process be required in each country?
Mr. Sugimura: Yes, each country requires its own registration/approval. But, as far as we talk about the Japanese market, we are planning to offer it to the general public as a treatment in 2020.
Keiko: As you have already touched, for the start date in each country included in Question #15, each country requires a separate regulatory approval, therefore the start date will vary depending on the completion of such regulatory approval process in each country?
Mr. Sugimura: Yes, you are correct.
Keiko: Thank you. Question 16: There has been some concern that a procedure like this would not be affordable to the majority of the consumer public. An average hair transplant costs between $8,000 and $12,000 USD (827k – 1.2m Yen). Does your company anticipate this procedure costing less than, similar to, or more than a typical hair transplant procedure?
Mr. Sugimura: This may not be the answer you find interesting, but to be honest with you, we are currently still in research for some parts, so it is difficult for us to determine. Therefore, at this point we are not ready to discuss about the pricing range. Generally speaking, the price is usually expensive during initial commercial stage, and frankly speaking, we have to admit the same for our case as well. However, after that, as the number of patients increases, we believe that we will be able to better control the price, and we definitely should be able to do so. Therefore, this is our long-term plan, but we plan to eventually lower the price to the level at which anybody can benefit from this therapy.
Keiko: Thank you. Question 17: “The regenerated hair follicle germ will be packaged and delivered to a medical facility for use in transplantation therapy for the patient.” Patients have wondered: Does your company plan to partner with and license the collection procedure to local clinics in major cities around the world, to be shipped to Japan for culturing and amplification, and back to the clinics for grafting, or will all patients need to come to Japan?
Mr. Sugimura: As I mentioned earlier, when it is first offered, it will be offered to general public as a treatment not covered by health insurance, and we first plan to focus only on the Japanese market. We do this as we want to ensure the effectiveness and safety, in order to properly gauge the clinical effects. Then, within several years after that, we have our sights set on putting the technologies into use in the major markets such as US, Europe and Asia. So in this sense, yes, we are already considering this plan. As far as the business model to implement overseas, although we have not worked out the details yet, we are thinking of setting up the process of processing cells itself within each overseas market, by this I mean that we envision to establish a facility to process cells within each market for treatment in order offer this therapy.
Keiko: Question 18: Surgeon skill plays a significant role in creating a natural looking result. As part of the previous question, do you plan to license this technology to surgeons worldwide, or do you have any plans to create devices which may help automate the grafting process to make results more consistent and uniform?
Mr. Sugimura: Actually as regards to this point, for the regenerative treatment that we first think of, we have already incorporated the marketability considerably. Therefore, in that sense, we have consciously developed a highly versatile business model wherein surgeons’ skills used in existing hair transplants may be utilized, unmodified. However, on the other hand, as you pointed out, we recognize that surgeon skill plays a significant role. So, at the initial phase, we also plan to use only the surgeons having the level of skills which meets our criteria in order to enables us to ensure stable effectivity and safety. Eventually, in the future, we plan to transfer our technologies to surgeons at clinics in order to increase the number of certified surgeons certified in order to have our technology widely used. As for the last question of automating the transplanting process, as Toyoshima has touched on this earlier, we think that automating the transplanting process is an effective means to ensure stable effects. Therefore, we would like to consider developing a device to automate follicle transplants in the future.
Keiko: Question 19: Also as a follow-up to the previous 2 questions: If this method succeeds, demand will be in the hundreds of millions of people. Can you describe your current thinking on how production could be expanded to meet such a large demand?
Mr. Sugimura: At this point now, we have already started considering about production stability and efficiency. And, as we announced in the recent press release, this led us to reach an agreement with KYOCERA Corporation to jointly develop cell processing devices, etc. to produce follicular primordiums. Eventually, we believe that not only automating the follicular primordium production process, which is only a part of the entire production process, but also automating the entire production process will enable us to further increase the production capacity efficiently. We are also considering to set up treatment locations or cell processing bases in major cities around the world. Therefore, in order to achieve this, we will need to establish a system/structure which allows us to offer our therapy at a broader range of locations including clinics. As a company, by increasing the production capacity, we aim to offer our service to about 10,000 patients a year around the world, therefore we recognize the need for developing a system/structure which enables us to achieve this goal.
Keiko: Question 20: An interesting idea came from one of our users: Can cultured and amplified cells be stored in cryopreservation for future use in the same individual? We call it a “top-up/top-off session” in the USA. This basically means ongoing additions to maintain or improve density or appearance as hair continues to degrade from the effects of androgens.
Mr. Sugimura: Well, this question seems more related to the research aspect…. But I will tackle this by jumping straight to the conclusion. We actually have already started research and development for this, and based on our research, we believe that it is possible to freeze and store cells collected from a patient for future uses. By storing frozen follicle stem cells, a patient would have to undergo follicle collection process only once. When he/she requires additional treatment, his/her frozen cells would be utilized for production, therefore we believe that this would significantly reduce burden to a patient for his/her 2nd treatment and onwards, and also in terms of continuous treatment, this would significantly improve the level of contribution to a patient. In terms of such market needs, we are glad to hear that your website members are talking about it because we launched this project with this idea already in our plan.
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