Column

Column

How the important people view?

Leading regenerative medicine research in Japan (3) -All 3 episodes-

Dr. Teruo Okano

Photo:Dr. Teruo Okano

Dr. Teruo Okano

Moving medicine out of the realm of art

Interviewer :
Do you think that sheets of cells will help in the treatment of a large number of patients?

Okano :
Today it takes two weeks to produce enough cells to treat a single patient with corneal damage. As we have five production rooms in our cell processing center (CPC), this means we can only generate cells enough for about 10 people per month, and in actuality treat around 60 patients per year. I think that if we want to raise those numbers, we will need to move away from treating this as an art form (that relies on individual skill), and embrace technological developments. We are collaborating with a group in Hitachi, Ltd. to develop robots capable of automating the cell culture process. The idea is to create a system of about 50X50X50 cm space that can routinely produce cell sheets, and to operate several thousands of these simultaneously in a single "cell factory." We think that, in addition to corneal repair, such cell sheets may one day be used in treatments of the esophagus or heart muscle as well.
We are collaborating with former Tokyo Medical and Dental University Professor Ishikawa on a joint research project to develop regenerative therapies using cells of periodontal ligament and developing endoscopic operation using a new manipulator to treat patients with esophagus cancer or cardiac myopathy. We are also cooperating with Olympus Corp. to develop a manipulator that can handle a 3 mm-thick sheet of retina cells.

Cell sheets may be an effective technique for bringing iPSCs to the clinic

Interviewer :
I understand that you are now working on developing sheets of induced pluripotent stem cells (iPS cells).

Photo:Dr. Teruo Okano

Dr. Teruo Okano

Okano :
Yes, we're working on a collaborative project with Dr. Masayo Takahashi (of RIKEN Center for Developmental Biology) to develop iPS cell sheets for retinal applications. The problem with iPS cells, however, is that it may be quite some time before they are ready for clinical uses. Right now, the focus tends to be on developing new methods for generating iPS cells, but it seems that there is little thought going into how they might be used in medicine. It's clear that they cannot just be injected. It's an invention that Japan can be proud of, but if we want to see its promise realized, we need to think about how to make and use iPS cells and develop a clear pathway to the clinical, as they have done so in embryonic stem cell research successfully in other countries.
In the US, they have already developed techniques for generating iPS cells without introducing any genes, and Japan already lags behind in the patents.
Our cell sheet approach is useful in cornea repair, but iPS cells may find uses in the treatment of diseases of the pancreas, heart, liver, nervous system and retina, which I think is wonderful if realized, so the time to develop a clinical strategy that includes our cell sheet technology is now. If we wait another 10 to 20 years, we certainly fall behind.

Interviewer :
You mentioned previously that cells from the lining of the mouth can already be used in cornea repair. What would be the advantage of using iPS cells?

Okano :
For parts of the body that can be repaired using its own cells or stem cells, iPS cells will probably not be so important. But for organs such as pancreas, heart and liver, for which we are unable to culture and grow cells in large numbers, iPS cells may play an important role. If that becomes possible, new treatments combining the iPS cells and our cell sheet technologies might one day be developed. This is why following a broad collaborative strategy is so important at this stage.

Interviewer :
MEXT has already made an iPS cell roadmap…

Okano :
I agree that the idea of using iPS cell-derived cells in drug screening is a good one. It is also valuable to think about specific key issues, such as diagnostics, and developing safe cell lines that don't give rise to teratomas. In the U.S. under President Obama, they have already approved a clinical trial to test the use of human embryonic stem cell-derived cells in the treatment of spinal cord injury. Japan needs to devise its own competitive strategies that don't rely on the old paradigms and keep it from falling behind the other leaders in the field.

Bringing cell sheets to worldwide application

Interviewer :
The method you have developed relies on advanced nanotechnology. Do you think that has made it more difficult to gain widespread use?

Photo:Institute of Advanced BioMedical Engineering and Science Tokyo Women's Medical University

Institute of Advanced BioMedical Engineering and Science
Tokyo Women's Medical University

Okano :
I'm working on a number of collaborations right now, both in Japan and elsewhere, including with labs at Harvard and the University of Pittsburgh. Of course it would be difficult for others to use this if they had to start from scratch. So we ask people to come and train with us so that they can pick up the necessary skills.
We now have heart surgeons from the West, as well as China and other countries coming to us. In Japan, we're working with heart surgeons, ophthalmologists, and GI and thoracic surgeons, and we have other collaborators from Finland, France and Italy.
At our university, Dr. Ohashi has developed a sheet of mouse liver cells that expresses human proteins, which he was able to use to make a subcutaneous partial liver that continuously secretes human antitrypsin. Other liver and cell sheet constructs that secrete clotting factor VIII are being considered for possible clinical use.
If these types of regenerative approaches become possible, it will signal a shift from treating symptoms by hormone supplementation to treating the underlying conditions themselves, which will have a direct impact on lowering healthcare costs. Similarly, a move away from allogeneic products, which require lifelong immunosuppression, toward autologous ones, should yield a dramatic improvement in quality of life. Regenerative medicine can thus provide fundamental treatments that not only save patients but yield cost savings as well.

Interviewer :
What do you see as your role going forward?

Okano :
I think I need to find ways of creating value by developing biology-based methods using advanced technology to treat patients. At present, I'm using cells from dental pulp and other tissues in working toward regeneration of neurons. I have some ideas I'd like to investigate in the future, such as using cell sheets having neuron-like patterns to treat Alzheimer's disease, or as alternatives to mechanical pacemakers.
Developing a three-dimensional culture of cell sheets to build thicker tissues is another issue for the future. Right now, we can make tissues having a thickness of millimeters from cell sheets having a thickness of 100 μms . It would be wonderful if we could one day use this technology to reconstruct hearts, kidneys or livers.

On spurring innovation, especially in Japan's medical arena

Interviewer :
We'd like to hear your views on how to support innovation, particularly with respect to medical development in Japan.

Okano :
I think that in Japan not enough thought is put into how to cure patients with intractable diseases. In the U.S., there is a large research facility located right next door to every major hospital where they try to develop strategies for exactly these patient groups. The NIH spends the equivalent of 3 trillion yen a year funding this work. This allows medical product and device makers to earn enough profit through healthcare spending in other markets. Japan's medical industry is not very competitive on the international level, however, and cannot cover medical care costs in Japan.
For example, we cannot manufacture pacemakers locally and need to import 100% these devices; similarly, 78% of catheters used in Japan are foreign made. Japan has world-leading electronics and polymers technologies, but due to risk aversion or regulatory issues, its industries do not enter medical markets. They continually shy away from enterprises that they perceive as risky.
New technologies should be developed for patients in the world. But Japan's Ministry of Health, Labor and Welfare are only concerned with our 120 million or so people. In the EU, medical development is a region-wide endeavor, and it is the duty of medical technology developers to consider the entire EU, which has a unified code for regulatory approvals as well. It's a regional system created to support both physicians and patients.
At our institute, we try to encourage young physicians and help them pursue their dreams, but I think both society and the university need to get behind them and support these highly motivated individuals. It is very important to provide strong support if we are to achieve world-class research. Our institute currently have 30 MDs and 40 Ph.D.s on staff, working at the interface of medicine and engineering in as open as possible an environment for the development of advanced medical technologies, with few walls in our open-framed labs.

Interviewer :
Any words for Kyoto University Professor Shinya Yamanaka?

Okano :
He has made a truly remarkable research achievement, and one that may someday earn him a Nobel Prize. But in order for us to attain the fruits of his work, we will need to go beyond working in the current frameworks and systems, and develop new means of supporting the building of a new field within Japan. I think this will require a new strategy for supporting the comprehensive development of cures. Without that, we risk squandering the efforts of our best researchers, such as Prof. Yamanaka.


Interviewed by Miwako Honma (supervisor of iPS Trend website), Katsuaki Sato (Japan Science Technology Agency)
Published on 30 November, 2009

  1. 1
  2. 2
  3. 3

Dr. Teruo Okano

Professor, Tokyo Women's University,
Director, Institute of Advanced Biomedical Engineering and Science,
Professor, University of Utah,
Member, Science Council of Japan

After receiving his Ph. D. in polymer chemistry from Waseda University in 1979, Dr. Okano served as an assistant and lecturer at Tokyo Women's Medical University (TWMU) before taking an assistant professorship at the University of Utah. He returned to TWMU as an assistant professor, and was appointed to professorship at both universities in 1994. He was appointed director of the TWMU medical engineering facility in 1999, and has served as the head of the Institute of Advanced Biomedical Engineering and Science at the same university since 2001.
His research interests include biomaterials, artificial organs, drug delivery systems, and regenerative medical engineering. He is particularly focused on how regenerative functions can be achieved by fine-tuning polymer structure. He developed the concept of cell sheet engineering, which first entered the clinic with bioengineered corneal epithelium. He hopes to extend to regenerative applications in the cardiovascular system, liver, and bladder as well. He is the director of the Japanese Society for Biomaterials, and a member of the board of the Japan Society of Drug Delivery System, the Japanese Society for Tissue Engineering, and the Japanese Society of Inflammation and Regeneration.

Awards and Honors
1990, 1995, 1996 Outstanding Paper Award from the American Controlled Release Society
1992 Japanese Society for Biomaterials Prize
1997 Clemson Award for Basic Research
1998 Society of Polymer Science Japan Prize
2000 Founders Award, Controlled Release Society
2000 Fellow, Biomaterials Science and Engineering
2005 Leona Esaki Prize
2006 Nagai Innovation Award, Controlled Release Society
2009 Medal with Purple Ribbon for scholarly or artistic achievement

Movie

See more

Page top

Movie

Movie

  • MEXT
  • Japan Science and Technology Agency
Page top