Interview

Dr. Miyata (hereinafter referred to as “M”), REPROCELL (hereinafter referred to as “R”)

R: Could you tell us more about your background, Dr. Miyata?

M: I originally studied in the Faculty of Science and Engineering to become an engineer developing space technology. However, by the time to choose a laboratory, I became fascinated with medical device development and decided to develop an artificial heart. As I developed it, I began to think that I wanted to use this artificial heart for actual medical treatment, but as an engineer I was not allowed to actual conduct clinical trials. Therefore, I decided to transfer to medical school and pursue the development of an artificial heart as a physician.

R: You made a drastic career change from engineer to doctor.

M: That’s right. I actually went on to become a doctor, and while treating heart disease as a cardiac surgeon, at the same time promoted the practical application of artificial hearts and regenerative medicine. However, Japan did not have an efficient system for approving new treatment methods, and it has been difficult to put them into practical use. Therefore, I joined the Ministry of Health, Labour and Welfare (MHLW) and engaged in the reform of Japanese healthcare, starting with the revision of the Pharmaceutical Affairs Law and the development of a new regenerative medicine law, the first of its kind in the world.

R: You have participated various reforms in terms of the system. What happened to the artificial heart that you developed?

M: Most of the artificial hearts I was involved with in the clinical trials have been officially approved and are still being used to date. It has been a long road, but I am very happy to be able to apply what I was worked on to help patients.
The artificial hearts currently in use cannot mimic all cardiac functions, the patient will eventually require a heart transplant. Even so, the fact that artificial hearts can be used as an option of treatments and tailored to the patient’s condition is a great step forward.

R: You have played a very important role in the treatment of heart disease.
How is the progress of regenerative medicine in other areas?

M: I am sure that regenerative medicine will advance in all fields in the future. Among these, the fields that has achieved remarkable progresses nowadays are Ophthalmology, Cardiology, and Neurology. For example, many patients are suffering from AMD (Age-related macular degeneration), a medical condition that causes vision loss or eventually blindness due to age-related damage to the macula. There is a possibility that it could be reversed/cured by using iPS cells.

R: Diseases that were difficult to recover from in the past now have a chance to be cured by regenerative medicine.

M: For example, in Cardiology, technology is advanced to restore cardiac function by applying cell sheets made from stem cells and iPS cells extracted from leg muscles to the heart. Furthermore, in Neurology technologies that use cells differentiated from iPS cells to treat Parkinson’s disease has been studied.

R: So regenerative medicine is being studied for various diseases.

M: It is conceivable that services such as Personal iPS, in which the person’s own cells are stored to prepare for future illness or injury, will become a major service in the future. Storing iPS cells in advance may be a promising method in a field where every second counts since it can shorten the time for the treatment. For example, if store your child’s iPS cells at a young age, hypothetically if they suffer a spinal cord injury in an accident, you may be able to start treatment immediately, thereby reducing the degree of residual damage.

R: So, it is beneficial for each person to store his/her own iPS cells as a risk measure. How do you see the future of regenerative medicine, including such new technologies and services?

M: It is thought that the possibility of regenerative medicine using one’s own iPS cell stock may expand. In addition, the use of iPS cells to select more effective drugs with less side effects will also expand in the future. In all fields, we will enter an era in which treatment methods and medicines will be customized for each individual. For example, even if a patient with severe liver cirrhosis or liver cancer, there are high hopes for the treatment of a mini liver transplantation that reproduces the function of the organ using one’s own iPS cells will be available.
In addition, if it becomes possible to store Personal iPS cells and perform regenerative medicine as soon as possible for various major illnesses and traumatic injuries caused by sports, traffic accidents, etc., the risk of major aftereffects may be reduced. Combining regenerative medicine and rehabilitation, I feel that people are becoming more and more hopeful that they will be able to walk on their own and enjoy traveling again.
With Japan’s population declining year by year, it is very important for each and every one of us to be able to lead a vibrant life and play an active role in society. As medical care continues developing, even if a person suffers a serious illness or life-threatening injury, there is a possibility that they will be able to return to their normal life and continue working or studying when the regenerative medicine is advanced enough. I believe that regenerative medicine using iPS cells will become one of the treatment options.

Aiming to Solve Donor Shortage
with Artificial Liver

Dr. Yagi (hereinafter referred to as “Y”), REPROCELL (hereinafter referred to as “R”)

R: Can you tell us more about your research?

Y: My research focus on replacing diseased livers with healthy livers made from cells. The liver is an organ with diverse functions, such as synthesizing proteins and breaking down toxins. It is called the “silent organ” because it barely shows any symptoms if it is not under severe damage.
However, hepatitis may develop due to the progression of fatty liver, excessive alcohol intake, viral infection, etc. If hepatitis persists for a long period of time, it can lead to cirrhosis, which is difficult to treat with medication, and liver transplantation may be considered.

R: It must be awful to have a undergo transplant operation.

Y: Yes, it is. Every transplantation requires a healthy donor. Even though liver has the highest regenerate capability of all organs, making it a viable organ for living donation, it is difficult to find a suitable donor, and many of them have to wait for the donation from brain-dead patients. In addition to being unable to receive transplantation, which places a heavy physical and mental burden on the patients.

R: That’s why liver transplantation in the regenerative medicine, which you have been studying, is attracting so much attention, isn’t it?

Y: Exactly. My goal is mass-culture liver cells made from iPS cells, filling them into a collagen skeleton, and making them function as an artificial liver. We believe that if it becomes possible to create artificial liver, it will solve the shortage of donors and benefit the patients who could not receive treatment before.

R: What is the current stage(states) of your research? Are there any issues to be resolved in the future?

Y: Currently, we are in the middle of non-clinical trials. We hope to advance into practical application within the next 10 years. There are still many challenges to be overcome in the creation of artificial livers, but one of them is the need to select cells that are compatible with the patient and will not cause harm in the body. The term “cells” varies widely, and iPS cell-derived liver cells from a non-patient are not necessarily compatible with the patient’s body. There is a view that it would be ideal to create an artificial liver using iPS cells made from the patient’s own cells, but this is not realistic at present due to the cost and lengthy preparation period. However, if iPS cells that can be used for treatment are stored in the future and artificial livers can be created smoothly, such a dream treatment may become a reality.

R: So, it is important to be able to smoothly prepare for treatment with cells that perfectly match the patient.
Besides your research, are there any other areas in regenerative medicine that you would likely to challenge in the future?

Y: I have established a venture company that develops materials for medical use, I believe that it is also important to develop treatment methods that use new materials to repair damaged body parts without using cells. On the other hand, some of the serious diseases actually require cell or organ transplantation, I believe regenerative medicine for various organs, including liver transplantation, will also advance. In addition to the liver, the non-motility organs such as pancreas and kidney, have relatively high potential to be the targets for regenerative medicine.
In addition, regenerative medicine may be applied to cosmetic field. If the differentiating process of iPS cells can be strictly controlled, it might be possible to cure skin damage fundamentally.

R: From various directions, research and development of treatment methods for diseases and injuries that could not be cured in the past is being conducted. I look forward to future developments.
Finally, what do you think is the “future of regenerative medicine”?

Y: In the future, as technology advanced and diagnostic techniques improved, it will be possible to predict the diseases at an early stage. In this way, we may be able to strengthen the function of the organ beforehand, or to replace it in some case. We believe that regenerative medicine can be an excellent medical treatment that can cover a wide range of areas, from “disease prevention” to actual treatment.
It is important that the right treatment for the right patient be given at the right time. The longer it takes to treat a disease, the more likely it is to be too late. Therefore, if each person could store their own iPS cells, it would greatly shorten the preparation time for treatment, and it might be considered to be an effective treatment strategy.
From a larger perspective, I also believe that personalized medicine will become more advanced. Today, people are able to receive various services such as shopping and meals in the comfort of their own homes. Among these services, only medical services still require a trip to a clinic or hospital. I believe that in the future, people will be able to receive appropriate medical services at home with a smartphone or computer.