In recent years, “exosomes” have attracted significant attention. These microscopic particles, produced by all cells in living organisms, were once thought to be merely a means for cells to dispose of unnecessary materials.
However, about 20 years ago, researchers suggested that exosomes might play a major role in intercellular communication. As a result, exosome research has rapidly advanced, gaining great expectations as a field with the potential to contribute to the understanding, treatment, and prevention of various diseases.
In this edition of Invent Innovation, an interview series featuring researchers engaged in cutting-edge scientific work, we focus on exosomes. We interviewed Dr. Ayuko Hoshino from the Research Center for Advanced Science and Technology at the University of Tokyo, who is working to uncover the role of exosomes in various disease processes. She shares in-depth insights into her research on conditions such as cancer, autism spectrum disorder, and pregnancy complications, as well as her future outlook, including plans to launch a startup.
What Exactly Are Exosomes?
— Dr. Hoshino, could you explain what exosomes are and what makes them so unique?
Exosomes are microscopic particles, approximately 30 to 150 nanometers in size, produced by all cells in living organisms. When they were first identified in the 1980s, they were believed to function mainly as a means for cells to discard unnecessary materials. However, about 20 years ago, it was discovered that exosomes released by one cell could be taken up by other cells. Today, it is thought that exosomes may serve as tools for intercellular communication.
Exosomes in the bloodstream (electron microscope image) (Courtesy of Professor Hoshino)
— In exosome-mediated intercellular communication, what kind of information is being exchanged?
The details are still largely unknown. Researchers are investigating the possibility that exosomes encapsulate specific molecules that convey information about the condition of the cells or organs from which they originate to the recipient cells or organs.
— How is the destination of a released exosome determined?
Our laboratory has reported that exosomes produced by cancer cells carry molecules that function like postal codes. It appears that the molecules contained within an exosome partly determine its destination. However, the full picture has yet to be revealed, and it remains unclear exactly how these molecules are regulated to control the targeting.
Additionally, existing research suggests that there are close connections between specific organs and cells. For example, exosomes released from the uterus and the ovaries — two organs located very close to each other — actually travel to different “preferred” organs. Even when originating from similar regions, their final destinations differ. It may be that the network of exosome-mediated connections between organs and cells is what allows the body to maintain its balance and function properly.
— How abundant are exosomes in the human body?
There are trillions of exosomes present in just 1 milliliter of blood. Considering the entire human body, the total number of exosomes is truly staggering.
— Recently, we’ve been seeing the word “exosome” more often in society. Are these the same exosomes you are studying?
No, the exosome-related products that have become popular recently are quite different in nature from what I study.
My research focuses on the role of exosomes within a single human body, including their relationship to diseases. However, the exosomes currently making headlines, particularly in the beauty industry, often refer to those produced outside the human body, such as from stem cells.
Stem cells, like mesenchymal stem cells, have the ability to differentiate into various types of cells within the body, which has given them a strong association with “rejuvenation.” Furthermore, there are some research findings suggesting that exosomes secreted by stem cells may help rejuvenate aging cells, which has fueled significant interest and high expectations in industries like beauty and wellness.
How Her Journey Into Exosome Research Began — From Cornell University to Cutting-Edge Science
— Could you once again tell us about your research theme?
As I mentioned earlier, my research aims to clarify the roles exosomes play within the human body.Why do exosomes exist? What functions do they perform inside the body, and how do they influence cells and organs?
If we can answer these questions, we may also be able to uncover the mechanisms through which healthy tissues develop into diseased states.
By analyzing the relationship between exosomes and various diseases, I aim to identify the disease-specific characteristics of exosomes, and further investigate whether there are commonalities in the changes occurring within the body due to different diseases—all through the lens of exosome biology. This is the focus of my daily research.
— What inspired you to study exosomes in the first place?
The major turning point came during my time as a graduate student, when I was studying cancer and became particularly interested in the mechanisms behind metastasis—the spread of cancer from a primary tumor to other organs and tissues.
At that time, I was especially fascinated by the concept of the “pre-metastatic niche,” which refers to environments within the body that are prepared in advance to facilitate cancer metastasis. In other words, metastasis is thought to begin even before cancer cells arrive at their future destination.
There was a laboratory at Weill Cornell Medicine in the United States conducting research based on this concept. Motivated by a desire to help reduce the number of deaths caused by cancer, I went to the U.S. after completing my graduate studies in Japan and joined Dr. David Lyden’s lab that had reported on the pre-metastatic niche.
While there, the professor leading the lab proposed a hypothesis: cancer cells might be directing the preparation of favorable environments at distant sites through exosomes. The research I began based on that hypothesis ultimately led to my current research focus.
Exploring the Connection Between Exosomes and Disease
— Your current research focuses on cancer, autism spectrum disorder (ASD), and pregnancy complications. What exactly are you investigating in each of these areas?
Regarding cancer, I am continuing the work I began at Cornell, focusing on elucidating the mechanisms of metastasis.
Currently, by analyzing individual exosomes, I am working to clarify how they are involved in the metastatic process.
— What are you investigating in your research on autism spectrum disorder (ASD)?
Autism spectrum disorder (ASD) is a developmental condition characterized by a wide range of traits, such as difficulties with social communication and strong preferences or fixations on specific spaces, people, or behaviors.
Because of differences in brain function, individuals with ASD may experience variability in what they can and cannot do in daily life. However, the exact causes of ASD remain largely unknown.
In this study, we are analyzing exosomes found in the blood of individuals with ASD and comparing them to those from individuals with typical development, while controlling for variables such as age and gender, to see if there are any distinguishing features.
— Have you discovered anything through your research so far?
Our findings suggest that there may be significant differences in the quality of exosomes found in the blood.
Specifically, our analysis showed that the exosomes from individuals with ASD contained a higher concentration of molecules related to blood cell lineages and the liver.
Since ASD is a developmental condition related to brain function, we initially expected to find distinctive features associated with brain-related molecules.
However, in the case of exosomes, characteristics linked to other organs and tissues appeared instead.
At this stage, it remains unclear whether these findings will lead to uncovering the causes of ASD or contribute to the development of diagnostic markers.
Further research will be necessary to explore these possibilities.
— Could you tell us more about your research on pregnancy complications?
In this area, we are targeting both the understanding of disease mechanisms and the elucidation of normal physiological phenomena.
I was personally amazed by this during my own experience of pregnancy and childbirth with my daughter, but during pregnancy, the mother’s body undergoes significant changes, including the remodeling of organs.
Our laboratory hypothesizes that these changes may be triggered by exosomes released from the placenta.
In fact, it has been found that placenta-derived exosomes differ in quality depending on the stage of pregnancy. Building on these findings, I am investigating how exosomes influence the changes in the maternal body leading up to childbirth.
Ultimately, this research may help uncover why the gestational period is approximately 40 weeks and why there is a massive release of oxytocin at the time of labor.
Regarding diseases, we have discovered that in cases of pregnancy-induced hypertension with renal involvement (also known as preeclampsia), certain exosomes may be contributing to an increase in urinary protein levels by placing stress on the kidneys during pregnancy.
Hoshino Lab official website: https://hoshinolab-edu.com/research/p1/
From Lab to Society — A Vision for Startup and Social Impact
— What are your future prospects for your research?
It has been six years since I returned to Japan from the United States.
Over these six years, I have conducted research across a wide range of diseases to identify the unique characteristics of exosomes in each condition as well as any commonalities across different diseases.
In terms of “broadening” the scope of my research, I feel that I have made significant progress.
Going forward, I plan to shift my focus toward “deepening” my investigations by concentrating on specific diseases, organs, or cell types—further understanding of ere exosomes originate, what molecules they carry, and what specific roles they play.
— As your research progresses, do you think there could be a future where exosomes are used for disease prevention or treatment?
I certainly hope so.
There is a possibility that exosomes themselves could become therapeutic targets.
I also believe there could be treatments that aim to reverse the “negative changes” that occur in cells after they take up exosomes.
To unlock the potential for prevention and treatment, much more research is still needed.
At the same time, we must also seriously consider how to create systems that enable the rapid implementation of basic research findings into society.
In fact, I am currently preparing to launch a startup company in collaboration with a business expert, aiming to bring the results of my research to society.
Unfortunately, in Japan, it remains quite difficult for basic research to transition into real-world applications.
This has long been pointed out by many researchers, and over the past five years, I myself have come to deeply feel how challenging the environment is for implementing basic science into society here.
If good research does not naturally find its way into the public sphere, then I believe we, as researchers, must proactively create those pathways ourselves.
I am determined to continue devoting my efforts toward building a future where more people can enjoy long and healthy lives.
Profile
Ayuko Hoshino
Professor, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo.
Dr. Hoshino completed her Ph.D. in 2011 at the Graduate School of Frontier Sciences, The University of Tokyo. She then spent over eight years at Weill Cornell Medical College (U.S.), where she progressed through positions as a postdoctoral researcher, Research Associate, and Instructor, before becoming an Assistant Professor.
In April 2019, she returned to Japan to join the International Research Center for Neurointelligence (IRCN) at the University of Tokyo as a Lecturer.
In March 2020, she established her own lab as an Associate Professor at the School of Life Science and Technology, Tokyo Institute of Technology, and since March 2023, she has served as a Professor at the Research Center for Advanced Science and Technology (RCAST), The University of Tokyo.
（Interview & Text: Teruko Ichioka / Photo: Kayo Sekiguchi）
