Japan IPS cell trial for vision to start in new incarnation

Masayo Takahashi, IPS cell trialIt’s been a long road, but the first ever IPS cell clinical study in humans is starting up again in a new incarnation. You might say it has been regenerated in a novel form.

Masayo Takahashi (高橋 政代) first started the pioneering IPS cell study a few years back in 2014, but it ended up getting put on hold in the summer of 2015 in the midst of changing regs in Japan and the discovery of some mutations in the IPS cell derivatives.

About a year after the hold was put in place, we got news that the study would be restarted in a new incarnation, and now more definitively the study is on track to start up again with 5 patients in Japan with the wet type of macular degeneration.  You can read the RIKEN PR here.

The PR provides more info including a co-leader:

“The project will be led by Yasuo Kurimoto and Masayo Takahashi of Kobe City Medical Center General Hospital, and Osaka University’s Graduate School of Medicine/ Faculty of Medicine, and will be conducted in collaboration with the RIKEN Center for Developmental Biology (CDB) and Kyoto University’s Center for iPS Cell Research and Application (CiRA).”

This is great news.

Yasuo Kurimoto is the surgeon who did the initial surgery in the study before it stopped.

One of the most striking things about the new form of this IPSC study is that it will reportedly focus on allogeneic use of IPSC rather than autologous. The foundation for this switch is that allogeneic cells derived from the IPSC can be used in matched recipients and in a relatively genetically homogenous population such allogeneic cells can be used in a number of patients with a good possibility that there won’t be rejection of the transplant.

Embryonic stem cell-based therapies can be used in the same allogeneic way and those are being studied for macular degeneration as well. I still feel like in the long run that the most power and unique positive contribution from IPSC clinically speaking may come from autologous use, especially in diverse populations such as the U.S. Their use in disease modeling is quite impactful as well.

10 thoughts on “Japan IPS cell trial for vision to start in new incarnation


  1. Okay, newbie question time. How can cells from someone else be less likely to be rejected than a person’s own cells? Is it like an apple selector rejecting a green apple but accepting a red-tinted orange?


    • It’s not necessarily that they’re less likely to be rejected, but that less money has to be spent developing a personal cell therapy for each individual because the allogeneic cells are look enough like the patient’s cells that the patient’s immune system tolerates them.

      If you have a population like Japan’s (mostly Japanese, some Chinese and Korean), you can cover the majority of major immunophenotypes with relatively few lines. I think Yamanaka’s lab reasoned that they could cover ~90% of Japan’s population this way (Paul, feel free to correct any mistakes). Thus, if you only have to make a small number of lines, you can spend less money generating the lines, hopefully leading to the therapy ultimately costing less.

      To use your analogy, it’s more like a red-apple selector allowing a green apple because it looks mostly like a red apple, but rejecting a red-tinted orange because it’s not an apple


      • I appreciate your response. I think I understand now. I forgot about the logistical challenges of applying personal cell therapy to every person.


        • Each persons cells display self-antigens on their surface which are recognized as foreign by the immune systems of other people. There are many such antigens (called HLA types) but those on the cells of related family members are closer than those of non-family members, so they are less likely to be rejected.

          This extends to the wider population in that the population comprises a number of HLA groups (more in US than Japan due to wider ethnic diversity). So if you are of a certain HLA group, you can receive cells from someone unrelated to you with la low chance of rejection.

          Hence, it is more economically feasible to bank stem cells of all the HLA types and be ready to treat anyone than it is to wait for a patient to appear and then try to make autologous tissue.
          .
          Note, there will always be some chance of rejection as there are many still unmatched antigens despite the HLA matching.

          Note 2, the eye holds an “immunoprivileged” position, meaning that there are fewer immune cells in the eye to cause rejection.

          On balance, this allogeneic strategy makes absolute sense in countries like Japan.


  2. I really, really, really hope that this comes to something. Basically, this is the condition that I have (although it was a very unusual form of mac-d and I heard a lot of “I’ve never seen this before” from eight doctors in a row.) So I have a major stake in hoping this works out. BUT… that having been said… I was one of the very few in 2014 and 2015 who was skeptical that the original trial *wouldn’t* run into any problems, which it later did. I put these thoughts into writing, and the comments are still archived here and elsewhere (so I’m not just saying it after the fact– there’s proof!) And look what happened. I have a really amazing track record of predicting bad things in other areas, in fact, but that’s another story!! 😉

    The point is that as much as I would love to see this study work out, and nobody wants it more than I do, I still do not know if the original concerns were addressed. I said it in writing in 2014 and 2015 when nobody agreed with me, I turned out to be right, and I’m saying it now. I would back the Astellas trials against these any day. YMMV, but again, look at my track record… 😉


    • Sorry to dent your “track record”, but the trial wasn’t stopped because it “ran into problems”. It was a proof-of-concept for safety of iPSC-derived RPE in man with one patient – so far it was successful. I guess you’re jumping on the bad-news bandwagon about mutations in the iPSC lines, but this was (a) not the reason the trial was stopped – that was due to changes in the Japanese regulatory framework to focus on allogeneic cells, and b) mutation testing was part of a normal testing program, as iPSC generation is mutagenic and testing will also happen in the future, and some lines will be discarded. If you check the posts on this blog by Masayo Takahashi, you would know that. How’s your track record on getting the facts first? 😉


      • Sorry but I believe that “running into problems ” covered what happened and what you said with those trials. The trials were stopped and that was NOT what had been originally predicted would happen. Check the original comments and you will see what I mean. Have you gone back and read all the comments on those original 2015 posts about the first trial? IMHO…when the trial was stopped when the original hopeful predictions did not include that happening… that sure counts as running into a problem. Just go back and read the original posts. .. You will see what everyone else was saying. If the trial being stopped for whatever reason when that was not predicted is NOT a problem. .. Then there must be a different definition of the word. Again,nobody could have much more of a stake in this treatment working out than I do. Most patients go way overboard with wishful thinking… I do not. I just will not go there… Which is also why I do not support illegal stem cell clinics. I have been there with all the desperation… I know what it’s like… But i am going to be rational… No matter what.


        • “Check the original comments…” I recommend you take your own advice – Masayo Takahashi explained it simply here, http://www.ipscell.com/2015/07/firstipscstop/ and said, “..the finding of the mutation was not something that called for a halt of the trial according to the protocol.”

          The RIKEN release that explains the reason for the delay in the trial is here, http://www.riken-ibri.jp/AMD/img/20150319.pdf and in case you don’t speak Japanese, it says the trial will move to allogeneic cells due to Japanese regulatory changes. Masayo’s comment was, “We are planning allogeneic transplantation, because we can treat several times more cases in the same time period than autologous transplantation with minimum immune response.”

          As a clinical researcher, we often pause trials if we think a change in some factor will provide better insight or patient benefit. These are not “problems”, they are routing clinical research procedures. Sorry Nostradamus 😉


  3. Thank you, Paul for describing this.
    I also think autologous will be the best and will be needed after some brake through.
    But for now, allogeneic is realistic to make a standard treatment.


  4. how can someone get this surgery from ? my mother is 65 and is blind in one eye going blind in the second eye rapidly and is not coping very well

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