Skip to main content
Regenerative medicine is expected to have a major effect on curing serious diseases, and it is iPS cells (induced pluripotent stem cells) that hold the key. Just like fertilized eggs, iPS cells have the capacity to become the cells that make up all of the body’s organs and tissues, such as the heart, brain, and eyes, and they can be used in a wide range of medical treatments. In recent years, research has progressed dramatically, and the countdown to clinical use has already begun. However, there are some considerable hurdles that must be overcome in order to actually use this technology in the field of medicine; the immense cost and effort required to culture iPS cells.
iPS cells are extremely delicate and easily weaken if they are not nourished and their waste are not removed continuously in a 37℃ environment. If even one bacterium contaminates the iPS cell, it will be rendered unusable, therefore growing cell culture is carried out in a sterile room, and all the work clothes, masks, and gloves are single use. Enormous costs are involved in operating and maintaining a clean room. In addition, regenerative medicine requires a large amount of iPS cells at once. For example, five million iPS cells are used for one treatment of Parkinson’s disease. The cell culture for multiple patients cannot be carried out manually without a multitude of skilled technicians and a clean room of appropriate size.
Sophisticated quality management and leading-edge facilities and equipment are essential to this kind of iPS cell treatment, which means the actual treatment can cost around 100-million yen. In order to mitigate these issues, in 2015 the research team at Hitachi Kobe Laboratory of the Center for Exploratory Research, Research and Development Group at Hitachi, Ltd. began working in collaboration with the Center for iPS Cell Research and Application at Kyoto University and Sumitomo Dainippon Pharma to take on the challenge of automating cell culture which can reduce the cost of iPS cell production for medical use by 100 times.
The theme under which the Hitachi Kobe Laboratory’s research team worked in collaboration with external leading experts in the field of regenerative medicine was the development of a closed-system, automated culture equipment, which completely upended the conventional concept of cell culture performed by hand in an open system. “To put it simply, it is an equipment that automatically cultures iPS cells in a completely closed space that can protect it from airborne bacteria, and the quality remains unchanged no matter who performs the work”. Project leader at Hitachi, Ltd., Shizu Takeda, spoke about the 17 years her team has dedicated to the research and development of this closed-system automated culture equipment.
“First, it took 10 years to create the foundation of sterility management. There was a long period of trial and error that was completely unsuccessful, and I thought numerous times that we would never reach our goal”. This was aggravated by the collapse of Lehman Brothers in 2008. As many corporations were paring down their R&D investment, Hitachi was also forced to temporarily freeze major investments. Takeda was propelled by her strong belief in the future of medicine, she struggled to ensure research and development funds.
In 2011, the Great East Japan Earthquake occurred. The strong shaking spilled the culture fluid that was in the manually operated open-system culture container serving as the control experiment, ruining the iPS cell culture. Meanwhile, the iPS cells in the closed-system automated culture container were completely unharmed. The disaster helped to prove the superiority of the closed-system automated culture equipment over the conventional open system. “As the start of iPS cell culture is calculated in reverse from the day of the transplantation surgery, delays in culture result in delays to surgery. The earthquake once again made us realize the importance of developing an equipment that takes into account earthquakes and other various disasters”, says Takeda.
That was not the only difficulty they encountered. When automated culture finally seemed to be on the right track, the iPS cells stopped multiplying for an unknown reason. Filled with uncertainty, the research team spent several months looking for a cause. They explored every possibility they could think of and still could not find the answer. Later when they found the cause in something completely unexpected, she said she was genuinely relieved.
It was truly a series of trial and error as they attempted to make their way through completely unchartered territory. Takeda recalls the reason they were able to overcome each individual hurdle as being the desire to take on the challenge of venturing into the unknown amongst the members of the research team at Hitachi Kobe Laboratory. In other words, she credits their pioneering spirit with their success. “During the time when we didn’t know whether or not we would be successful, everyone still believed that there was value in continuing our work. Right to the very end, they believed we would bring innovation to the field of medical treatment. That is why we were able to produce results, little by little, over a long period of time”. Though they met with many difficulties along the way in making the project a success, all of the team members agree that the driving force in overcoming them was “Hitachi’s founding spirit” (harmony, sincerity, and pioneering spirit). In promoting this collaborative effort, Takeda’s team was consistently insistent about being honest (sincere) and cooperative (harmony). This earned them the trust of their partners in the collaboration, and at the same time enabled them to demonstrate their pioneering spirit.
“Two years ago, when Hitachi’s research team moved from Hatoyama, Saitama to Kobe where our lab is located, I thought ‘this shows their high-level of commitment’”, Toru Kimura, from collaborative partner Sumitomo Dainippon Pharma, explains what a rare occurrence it is for researchers from different companies to work on developments collaboratively without any barriers in the same laboratory. “In such an environment, it’s impossible to keep secrets even if you want to (laughs). It is precisely because we have that relationship of mutual trust that we could be open about everything and we were able to have honest discussions. I was sure that if anyone could succeed, it would be this team”.
Professor Jun Takahashi of the Center for iPS Cell Research and Application at Kyoto University, who supports the research and development from a fundamental research and clinical perspective, also asserted that cooperative research cannot succeed if all members of the team are not sincere and open about their strengths and weaknesses. “Hitachi not only opened up their successful data to us, but they also made their failed data available to us. The fastest way to get things done is for everyone to examine what did not work and offer their knowledge to make improvements”.
After many long years of open innovation, they finally succeeded in commercializing the closed-system automated culture equipment in 2017. Still, Takeda states clearly, “Our ultimate goal was not just to create high quality cells, but to heal as many patients as possible using our technology. By automating iPS cell culture, we produce high quality cells in large volumes and use them to cure diseases that are difficult to treat, and we can make patients happy. We are not doctors, but we are capable of contributing to healing patients. That is our true goal”.
iPS cells, discovered by Nobel Prize winner Professor Shinya Yamanaka, brought great progress to regenerative medicine. Now, Takeda and the rest of the research team at Hitachi Kobe Laboratory have taken the first solid step toward the spread of regenerative medicine. “When we first started working on this 17 years ago, I didn’t know if this development was even possible. But as we got closer to making this dream come true, as long as we were willing to put in the effort, I experienced seeing that dream turn into a concrete goal”.
Takeda explains that though dreams are now closer to reality in the field of medicine, we are still far from seeing their widespread use. “It is true that the automated culture equipment is starting to be used, but it may take another 50 years before regenerative medicine becomes the norm. I may not be here to witness it”. If a time machines existed, would Takeda want to peek at what the future will look like? “Part of me would like to see what it looks like, but I don’t need to look because I have junior colleagues that I trust implicitly. They will take my work into the next generation and the spirit I infused into my work will remain”. For a brief moment, the glitter could be seen in Takeda’s eyes looking at what lays beyond the time machine reevaluating her current mission.
*This project was partially supported by the Japan Agency for Medical Research and Development (AMED).
The mission that Hitachi
aspires to fulfill in society
Contribute to society through the development of superior, original technology and products.
The values crucial to
the Hitachi Group in
accomplishing its mission
Hitachi Founding Spirit:
Harmony, Sincerity, Pioneering Spirit
What the Hitachi Group
aims to become in the future
Hitachi delivers innovations that answer
society’s challenges. With our talented
team and proven experience in global
markets, we can inspire the world.