Ryoma Ishii: Bioengineering Skills, Stem Cells and Transforming Healthcare

Ryoma Ishii is a Research Scientist in the Medical & Health Informatics (MEI) Lab, which he joined in June 2022, and has been a Visiting Scholar at the Harvard University John A. Paulson School of Engineering and Applied Sciences since 2019. He obtained his BS and MS degrees in Chemistry, with distinction, from the University of Tokyo, has worked as a bioengineering researcher and chemist at Sekisui Chemical Co., and served as a visiting scientist at Kyoto University. Early projects of note include work on a microfluidic chip for influenza diagnosis and a chemically defined, induced pluripotent stem-cell (iPS) scaffold for mass production. At Harvard, he has conducted organ-on-a-chip research, combining a microfluidic chip and cell analysis system. In his joint Harvard and NTT Research roles, he is collecting electrophysiological data of in vitro heart models, screening a suitable polymer for the surface of electrodes to measure the electrophysiology of the models and supporting the joint research project in other ways. Please read on to learn more about his background and current areas of research.

It looks like your early studies included a focus on optically active silane. How did your time at the University of Tokyo prepare you for what you did later?

As for optically active silane, this research was about the organic synthesis of silane compounds. I utilized the specific reaction that we wanted to use and was able to synthesize the silane compound, which has high optical properties. The key was to investigate a crucial parameter pertaining to the field. The professor had a device that measured circularly polarized luminescence (CPL) and allowed me to use the device. In the end, I was able to file a patent thanks to the high value of the CPL. Through this research, I learned that even though some knowledge doesn’t seem related to your research, it will help at some point in your career. Since then, I’ve always been eager to learn about new technologies and acquire knowledge to hone my skills as a scientist.

How would you describe your time as a visiting scientist at Kyoto University? That’s where you acquired induced pluripotent stem-cell (iPS) culture skills, correct?

I would say my time at Kyoto University was a harbinger of my career as a bioengineer. I was working on a chemically defined polymer for iPS cells. I’d already acquired synthetic skills for polymers, so my role at Kyoto University was to obtain skills and knowledge about the biology and stem cells.

Could you tell us something about your work on microfluidic chips and managing a lab at Sekisui Chemical Co.?

I was in charge of the 3D design of the microfluidic chips and also optimization of PCR [Polymerase Chain Reaction] reagents used in the chip. To account for all the steps of PCR, the design was complicated and hard to organize. Even so, I had to minimize the size of the chips because of the size limitation of the device. I overcame that problem by manipulating both sides of the chip. As for managing the lab, I worked on this when I was working on the polymer scaffold synthesis for iPS cells. At that time, no one was very familiar with the bio lab, so I learned the function and the layout of the typical biology lab and transferred the technology to the lab at Sekisui. I also calculated all the prices of the devices and had them installed at the lab. I needed some help from my former colleagues, but we were successfully able to create our lab, and it functioned well for the research.

You began your work as at Harvard focusing on a brain disease? How would you say that a system-on-chip model applies to drug creation or personalized medicine? 

Yes. I began my work at Harvard for an in vitro brain disease project. The research aims to recapitulate schizophrenia using fiber material and a specific set of extracellular matrices. I was trying to measure the differences in neuronal hormones between healthy and schizophrenic brain tissues by utilizing the chip I designed and fabricated. This chip system would help drug discovery because pharmaceutical companies can measure the reactions of neurons after adding medicine; they want to see the differences. As for personalized medicine, this method can be applied to stem cell technology, and the diseased tissues of patients can be created outside of the body. Then we can check the efficacy of each medicine using the tissues in the future.

As part of the new research with Harvard, you are now involved in collecting data and studying the material science associated with in vitro heart models, correct? Could you elaborate and share any other thoughts about this cardiovascular research? 

Correct. I’m making a biomimetic fibrous sample for the in vitro heart model. The aim of this research is to obtain a fundamental understanding of the electrophysiology and pump functions in our hearts. To maximize the pump function of in vitro heart samples, I am screening sizes, shapes, appropriate cell densities, and materials for a scaffold. As for results, I am evaluating them by using an optical mapping system to see the conduction velocity of Ca [calcium] imaging, immunostaining of actin and sarcomere, and particle image velocimetry to find the flow rate of systole and diastole. We are also trying to develop novel electrodes to measure the field potential of the samples to convert the electrophysiological data to an electrocardiogram. In this way, we can collect significant information about patients in the world for preventive medicine utilizing this measurement and stem cell technology.

Was there any course or professor or laboratory insight along the way that led you to your belief in the power of regenerative and preventative medicine to transform healthcare?
I’ve been curious about stem cell technology since Dr. Yamanaka got the Nobel Prize in Physiology or Medicine in 2012. And I’ve been fascinated with the idea that we can improve the quality of life of a lot of patients through regenerative medicine. This was why I asked my former supervisor to assign me to the iPS cell project in my previous job and why I came to the U.S. Nowadays, many people are excited to hear about new developments in medical technology and receive their benefits for a better life. I would like to be the one who takes the initiative to open a path for this kind of medical revolution.