Stellar Lab Radio, Episode 1 | Guest: Dr. Takanori Takebe
Creating organs from iPS cells. This once-distant vision of future medicine is becoming a reality, thanks to the work of pioneering researchers like Dr. Takanori Takebe. In this first episode of Stellar Lab Radio, we welcome Dr. Takebe, who was the first in the world to successfully develop a “mini liver” from iPS cells and now leads the field of organoid research.
Stellar Lab Radio is a talk program that shines a light on “world-changing research no one yet knows.” Leading global researchers share their cutting-edge work, the untold stories behind breakthroughs, and their visions for the future.
How does the meticulous approach unique to Japanese researchers blend with cutting-edge science? What are the origins and philosophy of Dr. Takebe, who has forged his own path as a scientist? In this first part, we dive into the roots of his research, the culture of Japanese science, and the importance of uniqueness in the age of AI.
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Sean：
Our very first guest is Professor Takanori Takebe, who holds positions at both Osaka University and Tokyo Medical and Dental University. He was the first in the world to create a mini liver from iPS cells and became a dual professor at the young age of 31. Since then, he has led laboratories at six locations across Japan and the U.S., remaining at the forefront of hepatic organoid research.
In this first part, we’ll explore the origins of his mini liver research, his uniquely Japanese approach in global research environments, and the current frontiers of work that could shape the future of medicine.
The Dream of Becoming a Transplant Surgeon: The Origins of the “Mini Liver”
Sean:
First off, I’d love to dive into your work. I imagine many people think of the “mini liver” when your name comes up, so I’d like to start there. What exactly is different about a mini liver compared to a regular liver?
Dr. Takebe:
The organ I mainly research is the liver. Originally, I wanted to become a doctor who could perform liver transplants—a transplant surgeon. But while I was in medical school, I realized that transplant procedures were extremely limited in Japan. The number of transplant surgeries performed is much lower than in other countries, which means far fewer opportunities to learn or practice.
Sean:
I didn’t know that.
Dr. Takebe:
Yeah. Compared to abroad, the number of procedures in Japan is drastically lower. If you want proper training in transplantation, you typically have to go overseas—like to the U.S. That’s what I did.
The very first patient I treated while training in New York happened to be Japanese, from Gifu Prefecture. He had traveled all the way to the U.S. hoping for a transplant. Eventually, he was able to receive a liver transplant and returned to Japan, where he continues to live a healthy, normal life.
But in Japan, he had already been told that treatment wasn’t possible. That reality shocked me.
Sean:
That must have been intense.
Dr. Takebe:
Absolutely. It was a miracle that he was able to come to the U.S., spend all that money, and manage his condition long enough to undergo the surgery. But it also revealed how many people in Japan can’t be saved due to limited access to transplantation.
And even in the U.S., there are many people waiting for organs—and the vast majority of them never get the chance. I had admired transplant surgeons because they “cure” patients, but I realized they’re actually “choosing” who to save. That revelation deeply unsettled me.
Around the same time, Dr. Shinya Yamanaka’s discovery of iPS cells was making headlines. It made me wonder: could there be another approach? That’s when I began researching iPS cells—and that path eventually led me to develop mini livers and mini organs.
Sean:
Let me go back a bit. What made you dream of performing transplants in the first place?
Dr. Takebe:
I had learned that transplantation was one of the few truly curative treatments in modern medicine. With most diseases, like the common cold, treatments are just symptomatic—you manage the fever, for example, but don’t address the root cause. That’s how most medicine works today.
But transplantation is different. It’s the only approach that actually cures the underlying condition. In that sense, it felt like the most “real” form of medical practice—something I really wanted to be part of.
Also, when I was in middle or high school, a very close friend of mine lost his father. He had undergone a living-donor liver transplant but unfortunately didn’t survive. That experience hit close to home and made me realize just how many lives couldn’t be saved in Japan.
From that point on, I was determined to go abroad and pursue this field. I think I first decided I wanted to work in liver transplantation during those teenage years.
“Research Isn’t Just for the Future—It Can Save Lives Today”
Takebe:
This might sound a bit heavy, but…
Sean:
No, it’s fascinating. I think this is exactly where communication design—or maybe even broader design—comes into play. You saw a societal issue you wanted to solve. You trained as a doctor, but realized the current system wasn’t enough. There are so many people in Japan who can’t access treatment. You began wondering if there was another way.
At what point did you decide to shift so dramatically from being a doctor to becoming a researcher? Was it when you first heard about iPS cells and thought, “This could be it”?
Takebe:
Honestly, when I entered medical school, I had zero exposure to research—none at all.
In the first and second year, as we studied more, everyone kept saying the same thing:
“We can diagnose this disease, but we can’t cure it.”
Or, “We’ve identified the target, but there’s no medication yet.”
And even worse: “We’ve confirmed the diagnosis, but there’s nothing more we can do. The patient will need to transfer hospitals—or just be discharged.”
There are so many situations like that. I faced them firsthand and realized that research wasn’t just about offering hope—it could change outcomes.
For example, in neurology, some conditions gradually shut down bodily functions. I once cared for an elderly woman who was slowly losing her ability to breathe, and there was no treatment. The doctors said, “We’ve made the diagnosis, but now we’ll just provide supportive care.” It was heartbreaking—especially since I’d gotten to know her well.
But I kept digging, and I found a paper published in Nature Medicine just a week before I took over her care. It was from a Japanese team at the National Center of Neurology and Psychiatry, announcing the start of a clinical trial for that exact disease. The paper suggested a new drug might actually be effective—something no one had ever used before.
So I took it to the neurology team and said, “Please take a look at this before discharging her.” At first, they were like, “Why is a student bringing this up?” I wasn’t in any position of authority.
But to my surprise, the head professor took it seriously—and in the end, she was enrolled in the trial.
I don’t know what happened afterward. It might not have been a complete cure. But what hit me was that science—real science—could offer a meaningful solution, even for patients who had no options left.
Until then, I thought of science as something that might help people 100 years from now. But this experience changed that. It showed me that today’s science can help someone not in 100 years, but tomorrow—or maybe even in the next few years. That realization was incredibly powerful.
That’s when I thought, “Maybe I can try this for a while.”
I actually planned to stop after three years and return to being a doctor.
Sean:
But you didn’t end up going back, did you?
Takebe:
Right. I never made it out [laughs].
A Turning Point from Cartilage Research to Mini Livers
Takebe:
So, returning to the topic of mini livers—around that time, Dr. Yamanaka’s discovery of iPS cells was making waves. I started thinking there might be potential there and wanted to try combining iPS cells with liver research.
But since I had no real experience with research as a student, I wanted to give it a try and see what it was like. After some twists and turns, I joined a lab—but when I said I wanted to work on the liver, I was told no. (laughs)
Sean:
Really?
Takebe:
Yeah, they turned me down. (laughs) Maybe it was the dyed hair and the vibe I was giving off—like I wasn’t serious enough. They basically said, “We can’t let someone like you work on such a prestigious topic like liver research.”
So they said the only open project that no one else wanted was on cartilage. I was like, “Wait, cartilage? Isn’t that the stuff we snack on at drinking parties?” (laughs) I was so naïve—I didn’t even understand why cartilage needed to be regenerated.
This lab was known for liver research, and no one was interested in cartilage. On top of that, the main supervising professor was based at the Kanagawa Children’s Medical Center, so he was physically distant and not available for hands-on mentorship. But they said, “If you’re willing to work on that, we’ll let you in.”
I wasn’t thrilled, but I figured, “Maybe this is just how things work,” and gave it a shot. I ended up working on it for four or five years. Looking back, it was one of the most transformative experiences of my life. Starting off not doing what I really wanted actually turned out to be a huge benefit.
I began applying the methods and protocols I saw being used next to me in the liver research—they were really solid. By taking that know-how and adapting it to a field no one else was exploring, I realized I could produce meaningful results. That experience laid the foundation for how I approach research.
So that became the root of my research. By the time I had finished my medical degree and had established a method that worked, I was finally allowed to pursue the theme I’d always wanted: “iPS cells × liver.” That led, about two years later, to the discovery of the mini liver.
Sean:
Got it. So what exactly is the difference between a mini liver and a normal liver…?
Takebe:
Ah yes, that was your original question, wasn’t it? (laughs)
I completely ignored it and launched into my origin story instead… Let me go back and properly answer that now. It’s a tough question, and I guess I subconsciously bought myself time by going off-topic. (laughs)
So—organs are huge inside the human body. The liver is the largest internal organ. What we use are iPS cells, which are essentially reprogrammed cells that behave like fertilized eggs. One cell divides and differentiates over ten months into about 30 trillion cells, forming complex organs like the intestine.
But we can’t recreate that entire ten-month developmental process in a dish, let alone replicate the postnatal growth. We’re limited to culturing cells for a few months at most—usually just a few weeks. In fact, one month is typical for what we do.
So when we say “miniature,” we literally mean small-scale versions of organs. For instance, in the liver, we recreate the structure and orientation of hepatocytes, the main liver cells. But instead of growing a full-sized liver that weighs several kilograms, we produce something that’s a fraction of a millimeter in size—about one-tenth to one-half of a millimeter.
From around 2010, our team and others around the world began creating these miniature versions of various organs.
In our case, we succeeded in producing small liver organoids—about one-tenth of a millimeter in size. We’ve shown that these mini livers can be transplanted into diseased animals to treat them, or used to model diseases in vitro.
By simulating liver diseases in a dish with these mini organs, we can replicate the conditions of serious liver illnesses in a very human-like way—on a petri dish.
So that’s how mini organs, including mini livers, are being used: as transplantable tissues and as models for disease research.
The Strength of Japanese Researchers
Sean:
By the way, how different is the process of creating a mini liver compared to creating other organs?
Takebe:
That’s a great question. Actually, like I mentioned earlier, a fertilized egg naturally develops into an organ over the course of pregnancy through repeated divisions and morphogenesis. So what we focus on is how to tap into that autonomous developmental ability.
To do that, a few key cues or directional signals are necessary. For example, think about how in life people often say, “I owe who I am today to that mentor” or “That teacher changed my path.” It’s kind of like that—key influences at specific stages, like in kindergarten or elementary school. We need to provide several such triggers at just the right times. The number of those triggers is actually not that large—maybe five or six.
So rather than a full human developmental process, we’re talking about strategically providing specific cues at specific stages to guide the cells. However, even with just five or six parameters, the combinations and intensities of those cues can vary greatly. And often, there’s no clear answer.
This is actually where the strengths of Japanese researchers come in.
When you’re dealing with countless combinations and trial-and-error in complex systems that aren’t governed by straightforward logic, you need an empirical approach—one where you try various things based on experience and observation. That kind of work is difficult and time-consuming. Yet, many of the world’s organoid breakthroughs have been achieved primarily by Japanese researchers.
For example, the very first organoid study—on the brain—was done by a team at RIKEN in Kobe. Then came intestinal organoids, developed by Dr. Sato, a Japanese researcher studying in the Netherlands. Kidney organoids were created by a Japanese researcher based in Australia who has since returned to RIKEN. Around the same time, a team in Kumamoto also developed kidney organoids. In short, many foundational organoid studies originated in Japan.
Sean:
Why do you think that kind of research is so uniquely suited to Japanese scientists? Is it a matter of cultural values or personal traits?
Takebe:
It’s probably due to perseverance and, to put it another way, perfectionism. Japanese researchers tend to fine-tune details to an incredible degree and optimize their work with extreme care. While researchers abroad may be very capable when it comes to executing established protocols or standardized procedures, Japanese scientists excel in the unstandardized, experimental phase.
For example, adjusting the concentration of a reagent just slightly—like using 90% instead of 100%—and doing that kind of trial across a huge range of conditions is something many others don’t typically do. But such subtle tweaks often turn out to be critically important.
When we’re comparing two conditions—say, condition A versus condition B—we might produce hundreds of mini-organs in a single dish and carefully observe the differences. If one condition produces just one mini-liver and another yields ten, that’s significant. You have to catch those differences through painstaking observation.
That kind of attention to detail, the deep commitment to incremental improvements, seems to be something Japanese researchers are exceptionally good at—or perhaps uniquely so. Researchers in Korea and other parts of Asia also work incredibly hard, but this specific trait is quite distinct.
Sean:
It’s really interesting. I’m American but I’ve lived in Japan for about 20 years and love the culture. There are so many aspects I deeply admire. But I hadn’t really thought about how cultural values influence research practices to this extent. The idea that a nation’s approach to everyday life might affect how scientific research is conducted—it’s fascinating.
Takebe:
I had an interesting conversation last week with an American visitor who told me they were deeply moved by something they witnessed here. People are often impressed by Japan’s fast, quiet bullet trains and such, but this time, it was something different.
Apparently, someone spilled coffee at a train station and meticulously cleaned it up themselves—wiped it up and threw the trash away properly. The visitor was blown away and said, “This is Japanese perfectionism!”
To us, that’s just common sense—if you spill something, you clean it up. But maybe that kind of behavior isn’t as common elsewhere. It made me think, “Ah, maybe this is why Japan excels in craftsmanship.” It’s about following things through to the very end, down to the last detail.
Japanese Perfectionism and the Challenges of Collaboration
Sean:
That’s really interesting. On the one hand, you’ve pointed out how Japan leads in certain cutting-edge areas of research, like organoids, where Japanese scientists are exceptionally strong. But on the other hand, I’ve heard that the number of top-tier publications and groundbreaking discoveries coming out of Japan has declined compared to a decade ago. Is that true?
Takebe:
Yes, I think one major factor is that the very way science is conducted has changed significantly. In the past, even a small team could make a totally novel discovery and publish it in a top journal. But nowadays, most fields require extensive collaboration.
Japanese researchers tend not to be very good at collaboration, and the language barrier makes it even harder to organize equal partnerships with international colleagues. In the U.S. or Europe, collaboration is assumed. People understand their own limits and delegate the rest to others—so things move fast. But in Japan, there’s a strong mentality of doing everything yourself. That slows things down. Sometimes, people even try to take on tasks outside their capabilities, which can hurt their evaluations.
So, in short, while the mode of science has changed, many in Japan haven’t adapted to that shift.
Sean:
That’s fascinating, especially because, culturally, Japanese society seems quite collaborative. There’s a strong sense of mutual care and responsibility. Like the example earlier, where someone cleaned up their own spilled coffee at a train station—it seemed like a sign of deep social responsibility.
Takebe:
That’s true in a general social sense, but in research labs, it’s different. In the early stages of a project, everything starts with an individual. Someone proposes an idea or begins uncovering something new, and only then do collaborations form. So the strength of the individual—of “the self”—is critical.
But many Japanese researchers are overly concerned with how they’re perceived by others. “What will people think of me if I do this?” or “Why is that person getting more recognition than I am?” That mindset creates hesitation.
In collaboration, you need to accept and embrace the differences between yourself and others—acknowledge that others will do different things, and that’s okay. But in Japan, there’s often a feeling that you must do as much as the other person or perform at the same level. That makes it hard to delegate or lean on others. So it’s not that Japanese researchers are inherently bad at collaboration—they just tend not to choose that path.
Sean:
How did you learn to collaborate?
Takebe:
Well, as I mentioned, I started out studying cartilage. At the time, everyone else around me was working on the liver, but no one was doing cartilage. My supervisor was based at the Kanagawa Children’s Medical Center, so I rarely saw him. And as a med student, I had classes during the day, so the only time I could do research was after 6pm. In that situation, collaboration was the only option.
I had to ask senior students for help with experiments and guidance. I’d go around asking, “I’m just a med student and don’t know much—could you help me with this part?” I even asked professors in other departments to read over my papers. I’d say, “I’m a student, and I’d really value your input, not just from my advisor but from different perspectives.” That’s how I managed to complete my early research.
So from the very beginning, I was collaborating. Not because I was particularly good at it, but because I had no choice. I didn’t have much time to do experiments myself, so I had to rely on others. That’s the only way I knew how to do research.
Sean:
There are so many incredible researchers in Japan doing uniquely Japanese research. If you had a message for them, would it be: “Let’s collaborate more”?
Takebe:
It depends on your research style. I started managing a lab relatively early in my career, and I realized that if I tried to compete with someone like Dr. Yamanaka, I’d never win—not in the same field. So I knew I had to work in less established areas where I could create new value.
If I tried to do legacy-style research in a well-established field, I wouldn’t stand out. So instead, I jump into fields that are still undeveloped or untouched—areas that may seem impossible but might be feasible through collaboration. I look for those opportunities, and if something promising starts to emerge, I try to grow it into a legacy field of my own.
That’s my style. I seek triggers outside of my comfort zone and solve problems through collaboration—not because I’m particularly talented at it, but because that’s my preferred approach.
Language, Collaboration, and the Impact of AI
Sean:
Thank you. Earlier, we touched on the idea that Japanese researchers could benefit from more collaboration. One obstacle mentioned was the language barrier. But with the recent rise of generative AI, things seem to be getting a lot easier. I’m curious—how much are people actually using these tools?
Takebe:
Oh, it’s like 99%. Almost everyone is using them now. Students write papers so fast these days! I ask, “Did you use AI?” and they mumble something vague, but I know they’re using it 100%. You can just tell—hyphenated phrasing everywhere, capitalized subheadings that look suspiciously polished. Even professional researchers are submitting papers where it’s obvious AI tools were used.
That said, I have some concerns—specifically about Japan.
Sean:
Are people using it too much?
Takebe:
Exactly. What worries me is that average, standardized thinking is creeping in through these tools. And that could flatten the very uniqueness that’s been Japan’s strength.
Take academic conferences, for example. International ones are always the same. Same themes, same titles, same speaker formats. But in Japan, you get things like “Intestinal Something Conference” or “World Something Symposium”—super vague or oddly translated titles. You get terms like “trunk body biology.” Stuff you’d never hear overseas.
It’s chaotic, maybe even a little “Galápagos,” but that’s what makes Japan unique. Our conferences don’t ride the global wave of standardization, partly because of the language barrier. But if everyone starts using ChatGPT and adopting the same structure and logic, that uniqueness could vanish.
For example, students’ proposals these days are painfully bland. I’ll think, “Did ChatGPT write this hypothesis?” Everything’s starting to sound the same. If that trend continues, in five years Japan might not feel any different from the rest of the world. And that would be sad.
Sean:
On the flip side, are there researchers in Japan who’ve managed to keep that “Galápagos-like” mystery or uniqueness alive, even while working internationally?
Takebe:
Yes—those are the ones who just don’t care what the rest of the world is doing. They’re off doing their own thing with small teams, completely shut off from global trends. It’s like they’ve entered a kind of self-imposed isolation, almost like a modern-day “sakoku” (national seclusion).
They tend to be craftsman-like in their approach—dedicated, self-contained, and fully immersed in their niche. On the other hand, researchers who are super social, always out networking, usually end up doing what everyone else is doing—just slightly earlier or in a new context. And then I think, “Well, if that’s the case, why not just do it at Harvard?” It kind of kills my enthusiasm.
Sean:
That’s really fascinating. One last question—only if you’re able to share: Since the mini-liver discovery, I imagine you’ve pursued various research directions through collaborations. Are there any recent projects that you personally find mysterious, cutting-edge, or uniquely exciting?
Takebe:
Yes, there’s one particularly unusual one…
(To be continued in the next installment.)
In the next episode, we’ll dive into Dr. Takebe’s most exciting current research and hear more about the passion driving his scientific journey. Stay tuned!
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