Top takeaways from new Yamanaka (山中伸弥) stem cell interview

Dr. Shinya Yamanaka

Dr. Shinya Yamanaka. Photo from CiRA, Kyoto University

Shinya Yamanaka is one of my favorite fellow scientists. His research is creative and rigorous along with having huge clinical implications. At the same time, Dr. Yamanaka sees the big picture and he’s very open about talking about real life as a scientist. I really appreciate both levels. In the past I interviewed him for my blog on the clinical use of IPS cells.

In a new interview with Yamanaka by The Japan Times, he says quite a lot of important things. The field should take note. Below I’ve listed the top bullet points from the interview. Note that he also talks about his father in a touching way and his own efforts to stay healthy with running.

  • Clinical outcomes from IPS cells are going to be broad. “We are now trying to bring iPS cells to patients suffering disease, for example, Parkinson’s disease, Type I diabetes, cancers. I believe that in the next 10 or 20 years, we can come up with many new treatments and therapies by using iPS cells and other related technologies.”
  • Difficulties and challenging times can be a foundation for future success in the biomedical field for scientists. Asked about struggles as a surgeon, Yamanaka said, “The answer was to become a medical scientist. I decided to contribute to medicine and patients in a different way, not as a clinician but as a scientist.” He also talked about challenging times during his training in the US and how things turned around, “in late 1998, human embryonic stem cells were reported for the first time. That was a big hit to me because we could help thousands of patients by using ES cell-derived brain cells or heart cells. That really activated me again. This is one reason how I overcame scientific depression.”
  • The current shift away from autologous use of IPS cells in Japan explained. “…we learned that autologous transplantation is very expensive and also it takes a very long time, at least six months…I think that, for the next five or 10 years, instead of autologous transplantation, utilizing iPS cells from healthy volunteers is the way to go. Such tissues generated from others are called allografts. By utilizing allografts, the cost can be much lower. We can also prepare cells [for transplantation] in advance…While there are many advantages of using allografts, the downside of using iPS cells from non-patients is immune rejection.”
  • Developing the IPS cell bank. “On the basis of a database of all Japanese HLA types, we have calculated that all we need is 140 lines (donors) in order to cover more than 90 percent of all the Japanese population.”
  • Anticipation returning to autologous IPS cell use in 5-10 years.
  • Skepticism on some working toward human immortality. “I don’t think that it will come true. On the other hand, we are trying to expand our “healthy life expectancy.”
  • How to avoid another STAP cell situation. Asked about STAP and misconduct cases, Yamanaka said, “I believe our area, the stem cell field, is very competitive. As many of our research results can lead to medical applications, many people like venture capitalists, venture companies are paying attention to us. That’s maybe one major reason how this kind of problem happens multiple times in our field…after the STAP scandal in 2014, more and more scientists in our field have become very careful. The No. 1 keyword for us is “reproducibility.”

7 thoughts on “Top takeaways from new Yamanaka (山中伸弥) stem cell interview


  1. Dear Paul, thanks for posting. On the issue of autologous vs. allogeneic iPS cells he says in the interview, “if we make iPS cells from some specific donors — more precisely, donors who have HLA homozygous alleles — we can minimize immune rejection after transplantation.”

    Do you know what this minimization will look like — some people needing immunosuppressives and others not — or is it all needing them but at lower dose? Has HLA matching already been tested for iPSC?


  2. Gary, a Japanese colleague told me recently that a set of 10 iPSCs could match the major HLAs of 50% of the Japanese population.

    There are two points worth bringing up. First, the homozygosity would be in the major HLAs- the cells would not be a perfect match for minor antigens that may still interfere with engraftment. Second, homozygotes are rare in the US…of the hundreds of iPSCs we’ve generated from an ethnically diverse American population, we’ve found only a couple of cases of homozygosity, and those only in one of the major HLAs. It would take a huge effort to develop a homozygous HLA iPSC bank for the US, and I don’t see that happening any time soon.

    We think that autologous therapy, in spite of the cost, is still the best approach in the US. Consider the cost of individualized immunotherapy (CAR-T therapy) for cancer- expensive, yes…works, yes…far better than other treatments.


  3. Jeanne, many thanks for these insights. If I understand correctly, the minor antigens will still cause some immune rejection in most, if not all, patients receiving allogeneic cells, so they will all need immunosuppressives. Not good.

    It makes sense for countries like Japan to go the allogeneic route in the short term, if they can cover 50% rapidly with only 10 lines (that’s breathtaking!).

    But Dr. Yamanaka said allogeneics will be good for 5-10 years and he would like to go back to autologous cells when methods improve and costs are down. By that time the pioneers of autologous therapies, like yourself, should have solved those issues (fingers crossed) and hence, those discoveries will be high value – regular visits to the patent office recommended!


    • @Jim,
      The years you are alive, even if constant, can be dramatically healthier ones.
      There’s a new concept emerging of a “healthspan” that combines the quantity and quality of life together.
      Paul


  4. I think the term “healthspan” is just a term used by certain scientists to avoid getting sucked into the debate around whether or not the technologies in their particular field will extend lifespan. I’d rather Yamanaka and other prominant scientists just said “I don’t want to speculate on that possibility” rather than denying it is possible at all. On the other hand would not emphatically denying something be taken as a tacit endorsement?

    Thinking about extending lifespan is always a controversial subject, as people have already accepted a 60 to 80 year life span mentally, and don’t want to get their hopes up only to have them dashed. Also not thinking about the awfulness of being old is a fairly normal coping mechanism, and disturbing that is uncomfortable for many.

    I’m just a layperson, but as I understand it health isn’t something that is separate from a mysterious process called ‘aging’. People die due to being in poor health, not because they have a timer inside them somewhere. Ergo you can’t extend someone’s healthy period of life without very likely extending their overall lifespan surely?


  5. Healhspan, if that’s the term nowadays, seems to me to be defining the characteristics of a quality of life assessment rather than mitagating the end. At least that’s how I read Yamanaka’s comment. There’s a period of old age where if science can deliver some functional outcomes for degenerative conditions it would allievate a great deal of suffering and at the same time lower the burden on care & associated costs to the health system.

    There are many degenerative conditions that would benefit from advances in cellular treatments to address the above – being able to see and have sufficient memory to function as yourself being just a couple…

    Jeanne comes back to the issue of minor HLA mismatch – wondering if there’s merit in also exploring the banking of hpSCs in that regard as they are able to reduce the incompatibility factor by the cells inheriting a duplicate set of human leukocyte antigen (HLA) genes. Wouldn’t this allow for an easier creation of a US therapeutic stem bank for Allo use?

    Cheers

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