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.”

Yamanaka Interview on Clinical Use of Pluripotent Stem Cells

Dr. Shinya Yamanaka

Dr. Shinya Yamanaka.                                           Photo from CiRA, Kyoto University

I invited Nobel Laureate Shinya Yamanaka to do an interview on the future of clinical translation of induced pluripotent stem cells (iPSC).

He provides some intriguing new insights into the iPSC field and the broader stem cell arena.

PK: The Takahashi Team’s active Clinical Study using iPSCs to make RPEs to treat Macular Degeneration has generated a great deal of excitement. Can you please share your perspectives on the importance of this work and the team involved? 

SY: This is the first study to apply iPSC technology to human care. This is a very important study, because if it succeeds it will show that iPSCs can be safely used in humans and also their potential for cell transplantation treatment. We collaborated with Dr. Masayo Takahashi of RIKEN CDB by evaluating the safety of the iPSCs and iPSC-derived cells that were used for the cell transplantation. She is an excellent researcher, and I am not surprised that her team is the first to have succeeded in this transplant.

PK: Any cutting edge investigational clinical work such as this has some risks. Could you please comment on the potential risks in this iPSC trial? Are there some elements here such as preclinical data, the number of cells used, or the target tissue of the eye that lower risks?

SY: One of the major concerns is whether transplanted cells such as the RPE sheets will cause tumors. In our collaboration with Dr. Masayo Takahashi’s team, we evaluated the safety of iPSCs and iPSC-derived cells by genome and epigenome analysis. While we minimized the risk to a level acceptable for clinical trials, we really cannot confirm how the cells will respond until we actually do experiments with humans, which is why this project is so important. One advantage of treating age-related macular degeneration is that it is easy to detect any abnormalities in the eyes, which is why the disease is a good starting model for iPSC-based treatment.

PK: As the inventor of iPSCs did you imagine 7-8 years ago that a patient in a clinical study in 2014 would already have received an iPSC-based treatment? How was this rapid translation from bench to bedside possible?

SY: I was surprised that after the announcement of human iPSCs in 2007, Dr. Takahashi told me that she would bring iPSC to the bedside within five years. I thought it possible technically speaking, but doubted it could be done so soon, since we needed to improve the technology and get government approval. It took 7 years, which is remarkable considering the work required. Both the accomplishment and the speed at which it was achieved are testaments to Dr. Takahashi’s leadership and her strong team.

The rapid transition is because many bright and passionate people are in the iPSC field. The funding and infrastructure provided by the Japanese government is also a major factor, as these have encouraged excellent scientists to enter the field.

PK: We are also starting to hear more about Dr. Jun Takahashi’s Team’s important work towards using iPSCs to treat Parkinson’s Disease. Can you please tell us more about that?

SY: Prof. Jun Takahashi’s team at CiRA is working on cell therapy for Parkinson’s disease, aiming to transplant iPSC-derived dopaminergic neural progenitor cells into PD patients’ brains. Early results suggest this treatment can be effective, and his team has established the protocol for transplantation. They are now focusing on validating its safety using monkey models. We hope his work will soon reach the operating room within the next few years.

PK: What other clinical applications of iPSC technology are in the works and that might begin clinical studies in the next few years?

SY: There are two major clinical applications of iPSCs, namely regenerative medicine and drug discovery. CiRA has a number of researchers working on either or both. For regenerative medicine, Prof. Koji Eto at CiRA is working on generating platelets via iPSCs, and we expect this will also proceed to clinical research in a few years. Besides work at CiRA, a team at Keio University has a plan to conduct clinical research on patients with acute spinal cord injury in four to five years, while Osaka University and Keio University hope to transplant iPSC-derived cardiac myocytes into patients with heart diseases within a few years. CiRA is collaborating with these teams as well.

Regarding drug discovery, you may have heard recently of CiRA’s Prof. Noriyuki Tsumaki’s paper about statins effects on bone growth, which was published online in Nature last month.

PK: Some in the media are taking about a certain tension between clinical iPSC work in Japan and clinical iPSC work in the US. Do you believe such a tension exists and if so, why? What does it mean for the iPSC field overall?

SY: I am not sure what “tension” means. I understand that both competition and collaboration exist between the US and Japan.

PK: How do you view hESCs today? Are there hESC clinical trials or potential applications that are of particular interest? What is your view of the argument by some that hESC are no longer needed?

SY: Human ESC was a great discovery for regenerative medicine and also instrumental to the discovery of iPSC and the type of medical treatments we are aiming to apply iPSC. At the same time, the ethical issues that hESC possess mean that as iPSC technology improves, hESC will be less needed. Still, iPSC is a new technology, and its safety and efficacy still needs to be confirmed. In addition, there may be some therapies for which hESC are better than iPSC. Thus, I think basic and clinical research of hESC is also important and should be done in parallel with iPSC research.

PK: What excites you most about the stem cell/regenerative medicine field right now today?

SY: I am excited about the possible number of people treated with iPSCs. This field has great potential to provide treatments for currently incurable diseases. Hopefully, within 5 years, we will refer to Dr. Masayo Takahashi’s AMD work as just one of many patient studies using iPSCs.

PK: Where do you see the iPSC field and the broader stem cell field in say 5-10 years?

SY: It is pretty amazing how much it has changed in the past years, so predicting the next 5-10 years is very difficult. I certainly hope we will see more diseases being treated with iPSC and related technologies such as direct reprogramming. I also hope that iPSC will be used more widely and routinely in drug development.

PK: What advice would you give to young scientists today who are excited about a career in stem cells/regenerative medicine?

SY: Through biomedical research, you could help thousands of patients in the future. Stem cells provide unprecedented opportunities in stem cell therapy and drug development. Biology of stem cells itself is extremely interesting. I hope many young scientists will enter to this field.