Shiseido's 30 Years of Basement Membrane Research

Envisioning the Future of Skin from the Source of Skin Regeneration

August 29, 2024

Shunsuke Iriyama, Director of the Skin Beauty Value Development Department, MIRAI Technology Institute, Business Core Technology Center (left in photo)
Yuko Hachiya, Skin Shape Value Development Group, Skin Beauty Value Development Department, MIRAI Technology Institute, Business Core Technology Center (right in photo)

In 2024, Shiseido announced a new ingredient, "CoreXymide," opening a new era of basement membrane care. "Basement membrane," often referred to as the source of skin regeneration, has been the focus of Shiseido's research for over 30 years, dating back to the early 1990s. What kind of exploratory journey led to the discovery of "CoreXymide"? We spoke to two researchers who have been passing the baton of research from the past to the future.

―First, could you tell us about your current affiliations and roles?

Iriyama:　I am a director at the Skin Beauty Value Development Department at the Business Core Technology Center. So, I’m basically in charge of the basic research department, a department that specializes in dermatology and life sciences. Since I was a student, I have always wanted to be a researcher, spreading value to the world through basic research. Because cosmetics is a field that integrates various research areas, when I joined Shiseido in 2004, the company’s stance was to nurture in-house, not only researchers who had completed their doctoral programs, but also those who had completed their master's programs. My wish was to make strides after joining the company, and I was interested in creating value by integrating fields.

Hachiya:　I am researching skin "shapes" in the department led by Iriyama-san, focusing on wrinkles and changes in surface morphology due to aging. My mentor during university was Professor Toshio Nishiyama (former director of the Skin Biology Laboratories in Shiseido Research Center), who started collagen research at Shiseido. When I was a third-year student, he showed me an experiment with a "three-dimensional cultured skin model," something that was essential for basement membrane research. Finding it very interesting to see a structure like real skin being created in a culture dish using cells and collagen that had once been disassembled, I studied in Professor Nishiyama’s lab and then joined Shiseido. That's what led me to where I am now.

The History of Shiseido's Basement Membrane Research

―Today, we will be talking about the history of Shiseido's basement membrane care. The basement membrane, which has been a topic of discussion in the beauty world in recent years, has a history of over 30 years at Shiseido, starting with long-standing collagen research beginning in the early 1990s. In products around the year 2000, basement membrane care was discussed in the context of "early aging care."

Iriyama:　At that time, my senior, Amano-san (Satoshi Amano, former senior scientist at the MIRAI Technology Institute), was leading the research. He won awards at IFSCC^*1 and Marie Claire^*2 and his research results were a sensation. It was a major discovery at the time that the basement membrane seemed to be involved in aging, and it was the first time that the basement membrane was linked to prevention of aging. After that, as a cosmetics company, we continued our research and found that it played the role of a command tower for skin beauty, such as wrinkles, spots, and skin barriers. So, I talked to the departments that managed and compiled information within the company and the product development department, telling them that the basement membrane controls the essence of skin beauty ant that we could use this discovery for product appeal. However, the response was not very favorable.

*1：The International Federation of Societies of Cosmetic Chemists (IFSCC): Founded in 1959 by the participation of cosmetic technologists' associations from eight countries. An organization started up by cosmetic technologists around the world dedicated to the development of more functional and safe cosmetic technologies.
*2："Prix d 'Excellence" sponsored by "Marie Claire" magazine. Established in 1985. Known as the most prestigious cosmetic award in the world. Judging is done through voting by influential beauty journalists from fashion and beauty magazines representing Europe, including France, evaluating all new products launched in France during the year—excluding fragrances—for their innovation, effectiveness, usability, packaging, and balance of quality and price.

―Why is that?

Iriyama:　At that time, what was required was a clear appeal, such as what has an affect on what, and how. Like, for example, if something was related to all the following―spots, wrinkles, and whitening—the idea was that each brand should make an appeal for the respective conditions. I tried to convey the meaning of basement membrane care as a greater value, but it didn’t work then.

The Relationship Between Basement Membrane Research and Stem Cell Care

―Today, approaches targeting root causes, such as core training, and the rage about maintaining a healthy gut, easily reaches people’s hearts, but it was different then. So, you changed your appeal approach.

Iriyama:　When I was thinking about how to convey the value of basement membrane care, the source of skin regeneration, stem cell care was becoming a hot topic. The basement membrane is where epidermal stem cells exist. I thought that if we could convey that relationship, the value would be understood by the world. By linking stem cells to the basement membrane, dreams expand, and the meaning can be conveyed easier. I also reconsidered disseminating information from a business perspective. This was around 2015.

―It's interesting that researchers themselves consider ways to express their research results in a way that expands dreams.

Iriyama:　Research results are meaningless unless they are used by society, appreciated, and generate sales. This is how research further progresses. I think the point of a corporate researcher is to balance conflicting matters and not just relying on a business mindset or a basic researching mindset. The field of cosmetics is an interdisciplinary field where it is easy to do that. I thought positively that I would deepen my research with the tactile sensation of a researcher combined with a business sense, catching the waves of the world. I think it's good to have researchers of various types.

Hachiya:　I remember those days. I was shown how the results of research are realized in the world. I was doing research on the construction of evaluation systems at that time, and that was steps away from any application of research results, so I was inspired to want to produce some output as soon as possible when I saw Iriyama-san rapidly develop various proposals on how to disseminate information on research. I was still not sure how I could contribute to the company, so I was motivated to do what I can as soon as possible.

The Long Journey of Repetitive Zooming In and Zooming Out with Colleagues

―I sense the difficulty and value of daily research that may not even end in a generation. Walking this long journey, sometimes thinking you have achieved results, only to have it not accepted much. Thus repeating the process from a different angle….

Iriyama:　In the past, the discovery of a factor alone was news. These days at various academic conferences, people don’t just focus on one factor, but work on understanding what is happening in the skin as a whole and incorporating "omics research" that captures overall changes and phenomena. In other words, it’s now more about zooming out and having an overhead view. That's why we see more research from the perspective of conveying through concepts and philosophy. We also started to think that it is important to consider the timing of the times and that things need to be conveyed as a whole. Support from researchers in different fields within the company is also a great force. For example, creating a momentum to grow together even for research that has once been put on hold. I think this is an important source of energy when creating new value.

―Do researchers communicate with each other beyond their assigned areas within the company?

Iriyama:　Organizationally, it is vertically divided, but there isn’t a strange barrier-like thing (laughs). When I was young, I was scolded for being rude in my approach. Ways of proceeding and policies differ depending on the field, so I make sure I properly investigate things, have conversations, and gain trust. I think it's the reverse side of each person being responsible for advancing their respective research areas.

Hachiya:　Each field has its own methodology and is a high-level specialist so to speak, so if we seriously take time to consider things and have conversations, we are listened to seriously and given advice.

Announcement of New Ingredient "CoreXymide" in 2024

―In 2000, your senior, Amano-san, presented "Research on Skin Basement Membrane Care" in the oral presentation section of the IFSCC Berlin Conference and won the Best Award. According to company history, he pinpointed what is happening inside the skin at the initial stage of aging and developed Lipidure, an ingredient that can care for aging, early." And now, a new perspective has been added to basement membrane care with the new ingredient "CoreXymide."

Iriyama:　Let’s revisit the basement membrane. The basement membrane, composed mainly of collagen, is only 0.1μm thick and is located between the epidermis and dermis. This membrane has three roles. One is to connect the epidermis and dermis, the second is to control communication between the epidermis and dermis, and the third is to stabilize epidermal stem cells. In simple terms, it plays all the important roles for maintaining a healthy skin condition, and if damaged, it can lead to skin aging such as spots and wrinkles. At the same time, the function of stem cells is also inhibited. Therefore, it can be said that caring for the basement membrane will make approaching multiple skin problems simultaneously possible.

We identified two enzymes after about two years of searching as a factor that causes damage to the basement membrane. The enzymes are MMP-9 and heparanase. We started screening from a huge sample library based on the hypothesis that if a component that inhibits the activity of the enzymes is found, basement membrane care will make a big leap forward. This was around the end of the 2000s.

―What do you mean by a huge sample?

Iriyama:　I checked the precise number. There were 21,476 candidate ingredients. From among them, we evaluated and determined the ingredient "CoreXymide,"taking into account global deployment issues and safety issues, that is, what can be incorporated into cosmetics.

―Is the process of checking 21,476 samples based on a hypothesis a dream come true for a researcher? Or...

Iriyama:　It was tough. We’re not always sure what result we’ll get, and it takes time, energy, and money. But my boss solidly secured the budget, so I had no choice but to do it. Since it was something that didn’t exist in the world yet, I had to create an evaluation system from scratch by reading all kinds of papers. I was just holed up every day, repeating experiments from morning ‘till night. What saved me was that my research buddies would occasionally call out to me and take me out to get refreshed. If it hadn't been for that, I may have ended up in hot water. I think I was able to pull it off because I was young.

Hachiya:　I heard a legend about there being a tower of plates for the experiment. Apparently, the number of plates was so high that it reached the ceiling when stacked. Speaking of which, I remember seeing Iriyama-san present the efficacy data for these enzymes at an internal report meeting in my first year of joining the company. I was in a different group at the time, but I had learned the importance of basement membrane using skin models in university, so when I heard Iriyama-san saying that by inhibiting this enzyme you can repair so much of the basement membrane, I thought, "Wow, that's amazing!"

Iriyama:　I see. That's nice.

Hachiya:　I definitely thought I'd bring this up today (laughs).

The Research Spirit Passed Down

―Being able to witness the work of a senior colleague when you set out on the vast ocean of research after joining the company sounds nice. I feel the passing down of the spirit of research.

Hachiya:　I've been following the research of my seniors at Shiseido since I was a student, and I've always recognized that the basement membrane is important. So, I'm very happy that basement membrane care is now becoming widespread in society. It also makes me want to continue my research with confidence, and it motivates me to want to create a sensation of my own someday too.

―I guess it’s important to match the times and ride the wave. I got the image of passing the baton of research with conviction, aiming for the moment, and not just in one’s own generation, when results come out to the world.

Iriyama:　Hachiya-san and other researchers will follow in the footsteps and create a new future. I can't catch up with Amano-san, basically the father of basement membrane research, so I chase after him. And Hachiya-san will run after me...

―You can't catch up to your seniors? Even now?

Iriyama:　I will never be able to catch up. I chase after them because I think the backs of the seniors I’ve witnessed are beautiful. And even though I can’t catch up, I can’t but not keep running. The master-disciple relationship includes not only research results but also a way of being—as a researcher. This included is what makes a master. Every time I see Amano-san, his eyes are always sparkling, and he is investigating something. I go to academic conferences with the feeling of Hachiya-san being behind me. Something like that.

Seeking a Better World Through Research

―"The backs I've seen are beautiful." Perhaps because there is beauty in the research itself that endlessly continue, it resonates with the heart that seeks the beauty of people. To end, what does a better world realized through research look like to you respectively?

Iriyama:　It's hard to say, but... the world will be a place where wrinkles will no longer be an issue and whether or not you have wrinkles will be a choice. Above that, I think a world where people can be okay with their wrinkles (if they choose that), making a life with wrinkles a wonderful thing, is a good world. My ideal is a world where people can live expressing their emotions honestly through their expressions. That would be beautiful.

Hachiya:　I think it would be nice if we could create a reality where people are not disappointed by their changes. I aim to provide value with the goal of increasing the number of people who can live with the mindset that even if they experience changes, that is okay. Currently, I don’t feel negative about myself aging, and I consider it a process of growing my own uniqueness. And, I hope to embody that in my research.

―It's a bit of a mean question, but if Shiseido were to steer towards the goal of "Looking younger than now at all cost! That is, anti-aging being the absolute goal…will that make you rethink things?

Iriyama:　Hmm, I don't think that's going to happen, or will it? What do you think, Hachiya-san?

Hachiya:　Since I joined the company, I have never heard anything that would imply denying the current state of a person. Even if that was something that was actually possible, a message like that would be unlike Shiseido.

Iriyama:　I think it's good to have diverse ways of thinking. Rather than consolidating ways of thinking into one, Shiseido has a culture of affirming all things. Our predecessors also achieved results by accepting various things with such a mindset, and I think that's how the people who will come after us will be too. Maybe the message will change with the flow of time, but I think it's Shiseido-like to move forward by affirming all things.

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