Looking for “the origin
of beautiful skin”.
Menard Stem Cell Research

MENARD LAB

What is the origin of beautiful skin?
Since 2003, Menard General Laboratories
have been
engaged in stem cell research
in pursuit of an answer to this question.
The lab has brought a series
of new discoveries and research results
to the world,
and is even transforming
the very assumptions underlying our concept of beauty.

Here on the “Menard Lab” site, we trace
the history of our stem cell
research and
tell the story of the challenges and passions
that have inspired us and our colleagues.

STORY Research Story

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01

The hidden power of stem cells
and a story of unknown challenges.

“Why don't you look into stem cells?”
With this question in 2003, second-year researcher Seiji Hasegawa was given a new mission.
These days, stem cell research is considered an essential part of regenerative medicine, but back then, it was field that was barely known.
Surely stem cells, with their ability to regenerate body tissue, must be a source of beautiful skin.
Following this intuition, Menard entrusted this man with its stem cell research.
Where are the stem cells in the skin?
And how do we extract them in order to conduct research on them?

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02

A stem cell research project that examines the skin of 1000 people, to contribute to society by creating a brighter future.

Aiming of regenerate beautiful skin,
Menard has been pioneering stem cell research since 2003.
The company has made many discoveries and developed many new technologies along the way, but there is still much to learn about skin regeneration.
In 2018, Menard joined long-time collaborators Fujita Health University School of Medicine, Nagoya University Graduate School of Medicine, and others to launch a project to learn more about skin stem cells.

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03

A world-first
groundbreaking discovery,
linking the joy and beauty
of youthful skin.

Back before the project to analyze the skin stem cells of 1000 people, Mika Hotta was conducting research under the guidance of Professor Hirohiko Akamatsu at the Fujita Health University laboratory.
While she was performing many analyses of skin, something attracted her interest. As people get older, differences start to appear in the skin of individuals, even those who are the same age.
It was already known that the stem cell count declined as people get older, but what accounted for these individual differences?
At any age, youthful-looking skin has a large number of stem cells and a high capacity for stem cell proliferation and differentiation (regenerative capacity).

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STORY_01

  • Katsuma Miyachi Chief Researcher(on the left)

    Research Laboratories
    Applied Cell Research Group

  • Seiji Hasegawa Director(in the center)

    Research Laboratories
    Nagoya University-MENARD
    Collaborative Research Chair

  • Yuichi Hasebe Senior Chief Researcher(on the right)

    Research Laboratories
    Nagoya University-MENARD
    Collaborative Research Chair

STORY_01 The hidden power of stem cells:
A story of unknown challenges.

  • Where does beautiful skin come from?
    A new journey begins to find the answer.

    “Why don't you look into stem cells?”
    With this question in 2003, second-year researcher Seiji Hasegawa was given a new mission. These days, stem cell research is considered an essential part of regenerative medicine, but back then, it was a field that was barely known. Surely stem cells, with their ability to regenerate body tissue, must be a source of beautiful skin. Following this intuition, Menard entrusted this man with its stem cell research. Where are the stem cells in the skin? And how do we extract them in order to conduct research on them? Hasegawa started out feeling his way around everything. He visited universities, research institutions, and academic societies around the country in a quest for clues, working on his own initiative and assiduously gathering and absorbing the knowledge and technology that he would need. After two years of tireless research in cooperation with the universities and research institutions, in 2005 he discovered a protein that was exclusive to stem cells. Using this protein as a signpost, he searched for stem cells in the skin and found them in the epidermis and dermis. His next success was to extract the stem cells. With this, Menard suddenly became the leader in stem cell research in the Japanese cosmetics industry.

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    Hasegawa started out feeling his way around everything. He visited universities, research institutions, and academic societies around the country in a quest for clues, working on his own initiative and assiduously gathering and absorbing the knowledge and technology that he would need. After two years of tireless research in cooperation with the universities and research institutions, in 2005 he discovered a protein that was exclusive to stem cells. Using this protein as a signpost, he searched for stem cells in the skin and found them in the epidermis and dermis. His next success was to extract the stem cells. With this, Menard suddenly became the leader in stem cell research in the Japanese cosmetics industry.

  • History had changed overnight as Menard made a global, state-of-the-art impact.

    One of the key moments in Menard's stem cell research was without doubt the introduction in 2006 of “Fluorescence activated cell sorting (FACS)”, the cell separation device. The cutting-edge FACS device, imported from America, was the first and most advanced of its kind, and at the time there was only one was installed in Japan.
    One of the young researchers who were excited about the new acquisition was Yuichi Hasebe. Using the specialized device enabled him to efficiently isolate only the stem cells he was interested in, and this dramatically accelerated his research.
    However, it was extremely delicate work, as he was dealing with living cells. Should the cells die, the whole process had to be started again. Every morning he would peer into the microscope, hoping and praying for results. When they didn't come after 50, 100 days, he even visited a shrine to pray to god for help. Finally, his diligent and tireless research bore fruit, and in 2006 he discovered that stem cells decline with age, and in 2013 that stem cells construct their own environment (SVA). Currently, Hasebe is producing major research results in the field of stem cell immortalization.

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    However, it was extremely delicate work, as he was dealing with living cells. Should the cells die, the whole process had to be started again. Every morning he would peer into the microscope, hoping and praying for results. When they didn't come after 50, 100 days, he even visited a shrine to pray to god for help. Finally, his diligent and tireless research bore fruit, and in 2006 he discovered that stem cells decline with age, and in 2013 that stem cells construct their own environment (SVA). Currently, Hasebe is producing major research results in the field of stem cell immortalization.

  • Taking the title,
    “innovation that makes people happy”.

    While engaging in a range of stem cell research, Katsuma Miyachi is taking on the challenge of developing artificial skin. In 2020, he succeeded in creating an artificial skin model using advanced stem cell and genome editing technology. With this, he was able to reproduce various kinds of skin problems such as skin roughness and blemishes at the test tube level. This had previously been impossible. In recognition of its ground-breaking nature, his work won a grand prize at “Japan Beauty Tech Awards 2021” under the theme of “innovation that makes people happy”, as an advanced technology that could be expected to play a role in the fields of beauty and healthcare.
    It was a valuable opportunity to reaffirm that artificial skin research can contribute to the happiness of people the world over.
    Menard currently has over 100 patent filings relating to stem cells, placing the company at the top of the cosmetics industry. Stem cell research that began with a single individual has now grown to involve close to 100 researchers in some capacity or other. In a creative research space that allows lively discussions and the free generation of new thinking and ideas, our researchers seek out the next innovation.

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    It was a valuable opportunity to reaffirm that artificial skin research can contribute to the happiness of people the world over.
    Menard currently has over 100 patent filings relating to stem cells, placing the company at the top of the cosmetics industry. Stem cell research that began with a single individual has now grown to involve close to 100 researchers in some capacity or other. In a creative research space that allows lively discussions and the free generation of new thinking and ideas, our researchers seek out the next innovation.

Affiliation and position as of November 2023
Interviewer:Midori Yamazoe (misto grafico)

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STORY_01

  • Takaaki Yamada Senior Chief Researcher (on the left)

    Research Laboratories
    Applied Cell Research Group

  • Yoshie Ishii Researcher(on the right)

    Research Laboratories
    Applied Cell Research Group

STORY_02 A stem cell research project that examines the skin of 1000 people, to contribute to society by creating a brighter future.

  • A place that can only be reached
    by approaching the truth in 1000 different ways.

    Aiming of regenerate beautiful skin, Menard has been pioneering stem cell research since 2003. The company has made many discoveries and developed many new technologies along the way, but there is still much to learn about skin regeneration. In 2018, Menard joined long-time collaborators, Fujita Health University School of Medicine, Nagoya University Graduate School of Medicine, and others, to launch a project to learn more about skin stem cells. This was the “project to analyze the skin stem cells of 1000 people”. Researcher Takaaki Yamada is working with the Fujita Health University School of Medicine to develop new skin regenerative medicine treatments. He shared his thoughts about the industry-academia collaborative efforts. “We are using cutting-edge technology to analyze stem cells in the skin of as many people as possible, with the goal of identifying the regeneration mechanism of skin stem cells. The overall objective is to contribute to society through research. Via academic societies and other channels, we widely share the results of our research, including the state of our skin regeneration technology, knowledge about preserving healthy and youthful skin, and more.” The project to analyze the skin stem cells of 1000 people is led by Hirohiko Akamatsu, Professor of Applied Cellular Regeneration Medicine, Fujita Health University School of Medicine.
    The research project aims to understand the regenerative mechanism of skin stem cells in order to develop skin regenerative medicine treatments. The name of the project reflects the desire to find the optimal regenerative medicine treatments for everyone, by analyzing the stem cells of as many people as possible.

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    Researcher Takaaki Yamada is working with the Fujita Health University School of Medicine to develop new skin regenerative medicine treatments. He shared his thoughts about the industry-academia collaborative efforts. “We are using cutting-edge technology to analyze stem cells in the skin of as many people as possible, with the goal of identifying the regeneration mechanism of skin stem cells. The overall objective is to contribute to society through research. Via academic societies and other channels, we widely share the results of our research, including the state of our skin regeneration technology, knowledge about preserving healthy and youthful skin, and more.” The project to analyze the skin stem cells of 1000 people is led by Hirohiko Akamatsu, Professor of Applied Cellular Regeneration Medicine, Fujita Health University School of Medicine.
    The research project aims to understand the regenerative mechanism of skin stem cells in order to develop skin regenerative medicine treatments. The name of the project reflects the desire to find the optimal regenerative medicine treatments for everyone, by analyzing the stem cells of as many people as possible.

  • Looking at skin, one person at a time.
    Listening carefully to the stories people tell.

    As one of the project members, Yoshie Ishii works at the Fujita Health University School of Medicine alongside professors from the university's Department of Dermatology who are researching skin stem cells. One of her major tasks is isolating and cultivating stem cells from skin tissue. Stem cells are always difficult to handle, and things do not always go smoothly. She feels a great sense of achievement when, through the trial and error process, she is able to successfully isolate and cultivate stem cells. At the same time, the fact that the work opens up new research possibilities in skin regeneration makes it very rewarding. The project is made possible through the cooperation of the people who support it. She communicates closely with the professors to build relationships of trust. “There's an extra sense of tension when working in an actual medical worksite. I want to work hard on the project, always remembering to be grateful for the many people support us”, she says.

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    The project is made possible through the cooperation of the people who support it. She communicates closely with the professors to build relationships of trust. “There's an extra sense of tension when working in an actual medical worksite. I want to work hard on the project, always remembering to be grateful for the many people support us”, she says.

  • Success, but the work goes on.
    A journey of never-ending challenges.

    In 2023, five years after the project was launched, the target was reached, and the skin of 1000 people was analyzed. “It really was a case of taking small steps every day, until one day, we had reached this big number. We could only do it thanks to the professors who worked with us, the patients who agreed to participate, and everyone else involved in the research who saw the promise that stem cell research holds”, says Ishii. Through this large-scale analysis of 1000 people's skin, we have discovered that senescent cells secrete substances that inhibit regeneration by stem cells, and that the appropriate removal of such senescent cells can kick-start regeneration by stem cells. We now have a fuller picture of the mechanism of skin regeneration, and everyone who has been involved in the project feels a great sense of accomplishment. At the same time, the more we researched this topic, the more we realized just how important stem cells are. Next, instead of a goal to analyze the skin of 1000 people, we want to conduct a deep analysis of the skin stem cells of individuals, and take on the challenge of developing regeneration technologies and conducting research into preserving each individual's healthiest and most beautiful skin.

Affiliation and position as of November 2023
Interviewer:Midori Yamazoe (misto grafico)

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STORY_01

  • Mika Hotta Chief Researcher (on the left)

    Research Laboratories
    Nagoya University-MENARD
    Collaborative Research Chair

  • Yuichiro Ogata Chief Researcher (on the right)

    Research Laboratories
    Applied Cell Research Group

STORY_03 A world-first groundbreaking discovery,
linking the joy and beauty of youthful skin.

  • The world's first discovery of the “regeneration blocker”
    came from a small, straightforward question.

    Back before the project to analyze the skin stem cells of 1000 people, Mika Hotta was conducting research under the guidance of Professor Hirohiko Akamatsu at the Fujita Health University laboratory. While she was performing many analyses of skin, something attracted her interest. As people get older, differences start to appear in the skin of individuals, even those who are the same age. It was already known that the stem cell count declined as people get older, but what accounted for these individual differences?
    At any age, youthful-looking skin has a large number of stem cells and a high capacity for stem cell proliferation and differentiation (regenerative capacity). The analysis of 1000 people's skin showed that senescent cells accumulate in skin that has fewer stem cells and stem cells with reduced capacity. Further, senescent cells produce and secrete various proteins that impair skin functionality (aging accelerants). For the first time ever, our research found that among these various proteins that impair skin functions, there are those that inhibit stem cell proliferation and those that inhibit stem cell differentiation. These are collectively known as “regeneration blockers”.

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    The analysis of 1000 people's skin showed that senescent cells accumulate in skin that has fewer stem cells and stem cells with reduced capacity. Further, senescent cells produce and secrete various proteins that impair skin functionality (aging accelerants). For the first time ever, our research found that among these various proteins that impair skin functions, there are those that inhibit stem cell proliferation and those that inhibit stem cell differentiation. These are collectively known as “regeneration blockers”.

  • A new skin mechanism and interpretation
    that revolutionizes the conventional view.

    Meanwhile, Yuichiro Ogata was conducting research largely focused on stem cells and immunity, and senescent cells. He had been making new discoveries and establishing new facts by using stem cell and immunity cell cultivation techniques. Senescent cells secrete aging accelerants that impair skin functionality. When these cells are allowed to remain in the skin indefinitely, they accelerate skin aging. However, research shows that there is a mechanism to remove senescent cells driven by agents in the skin such as immune cells, and that stem cells detect the removal of senescent cells and begin the regeneration process. However, this process declines with age, causing senescent cell build-up and a decline in the regenerative efficiency of stem cells. In other words, improving this set of functions is important for youthful skin. We named this natural mechanism, which removes senescent cells and efficiently promotes “regeneration”, “auto-purification”. “Auto-purification” is destined to be a major focus of attention, at the same level as “regeneration”, in next-generation beauty care.

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    However, research shows that there is a mechanism to remove senescent cells driven by agents in the skin such as immune cells, and that stem cells detect the removal of senescent cells and begin the regeneration process. However, this process declines with age, causing senescent cell build-up and a decline in the regenerative efficiency of stem cells. In other words, improving this set of functions is important for youthful skin. We named this natural mechanism, which removes senescent cells and efficiently promotes “regeneration”, “auto-purification”. “Auto-purification” is destined to be a major focus of attention, at the same level as “regeneration”, in next-generation beauty care.

  • Passion and a resolute approach
    open new doors to beauty.

    Over many years, stem cell research has passed through several turning points and accelerated rapidly. Although the research of Hotta and Ogata differed in focus and methods, the results came together to give us a fuller understanding of how stem cell-initiated skin regeneration progresses. This was the moment that a new beauty concept was born, one which can take us to a new level of youthful skin through a cycle of “regeneration” and “anti-aging”, followed by “auto-purification”. Today, in relaxed and cheerful workplaces, researchers continue to enthusiastically pursue stem cell research, their minds buzzing with ideas and plans. Whether it is by pursuing such useful avenues as preserving youthful skin by slowing, even a little bit, the aging of cells, or finding ways to make deteriorating cells work harder, we continue to open new doors to beauty with the originality and resolve that are the hallmarks of the Menard approach.

Affiliation and position as of November 2023
Interviewer:Midori Yamazoe (misto grafico)

RESEARCH

2023 to 2019: World's first discoveries
and a new stage of stem cell research
  • 2023
    • Discovering that the removal of deteriorating
      cells (senescent cells) is linked to stem cell skin regeneration
  • 2022
    • Discovering INHBA,
      a factor that inhibits stem cell proliferation
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  • 2021
    • Explaining the removal mechanism of senescent epidermal cells
  • 2020
    • Discovering that GREM2 increases in the skin with aging
    • Explaining the removal mechanism of senescent dermal cells
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    • Explaining the removal mechanism of senescent dermal cells
  • 2019
    • Discovering GREM2, a factor that suppresses stem cell differentiation
2017 to 2012: Menard's accelerating stem cell research
  • 2017/2016
    • Identifying the location of stem cells within hair follicles
  • 2015
    • Discovering that stem cell demethylation plays a role in blemish formation.
    • Identifying the location of stem cells in the epidermis and dermis
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  • 2013
    • Discovering causes of neck aging through stem cell research.
    • Joint research course established with Nagoya University
  • 2012
    • Discovering WNT1, a substance that promotes stem cell differentiation into melanocytes
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2009 to 2003: “Skin's starting point.”
The curtain rises on a new challenge
  • 2009年
    • Discovering that UV rays cause melanocytes with high melanin production to grow from stem cells.
    • Discovering that the psychological effects of fragrances energize stem cells
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    • Discovering that the psychological effects
      of fragrances energize stem cells
  • 2008
    • Establishing endowment course at Fujita Health University
  • 2006
    • Discovering that the stem cell count declines with aging.
    • Introducing fluorescence activated cell sorting
      (FACS) separator that efficiently isolates stem cells
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    • Introducing fluorescence activated cell sorting
      (FACS) separator that efficiently isolates stem cells
  • 2005
    • Establishing technology to isolate stem cells
  • 2003
    • Launching stem cell research

The Stem Cell-Beauty Connection

  • Question_01 What are stem cells?

    Stem cells regenerate the skin.

    “Stem cells” exist in the epidermis and dermis, which constitute our skin. The epidermis has cells that produce the skin's moisturizing agents, while the dermis has cells that produce substances that give the skin firmness, such as collagen. The role of “stem cells” is to produce such cells in the epidermis and dermis, and thereby regenerate the skin. In other words, skin regeneration performed by “stem cells” is important for keeping skin moisturized and firm.

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  • Question_02 What happens when stem cells decline?

    Signs of aging appear.

    “Stem cells” play a significant role in building beautiful skin. At the same time, we know that the number of “stem cells” can decline with aging, stress, or environmental effects such as UV rays. As the “stem cell” count declines, epidermal cells that produce moisturizing agents (keratinocytes) and dermal cells that produce collagen (fibroblasts) are replaced at a slower rate, leading to skin deterioration. Further, in Menard's research, it was discovered that as cells deteriorate, they secrete substances that block cell replacement. The effect of declining “stem cells” and substances that block replacement slow the regeneration of the skin, leading to visible signs of aging, such as dryness, wrinkles, and sagging.

  • Question_03 What happens when deteriorating cells accumulate?

    Aging accelerates!

    As cells continue to deteriorate, they eventually secrete a large amount of substances that cause skin aging. Therefore, it is important to prevent such substances from being secreted. In recent years, Menard's research has shown that skin has the ability to remove cells in the final stages of deterioration. As well, removing such cells stimulates stem cells to start regenerating the skin.

  • Question_04 What is the cycle that leads to youthful skin?

    A cycle of “regeneration, anti-aging, and auto-purification” is the key.

    Over many years of research, Menard has discovered the “three-function cycle” that leads to youthful skin. In the first step, “regeneration”, concentrations of stem cells expand and substances that block regeneration are suppressed, enabling stem cells to proliferate and produce new cells without hindrance. In the second “anti-aging” step, deteriorating cells are prevented from secreting substances that stimulate aging. Finally, the “auto-purification” step removes cells in the final stages of deterioration, boosting the ability of “stem cells” to start regeneration. This cycle of “regeneration, anti-aging, and auto-purification” helps take skin to a new level of youthfulness.

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Towards the beauty of the future Menard's Challenge Continues

As the pioneer of stem cell research in the Japanese cosmetics industry,
we have never stopped learning and evolving.
What can we do to provide youthful, beautiful skin?
In pursuit of an answer, Menard continues its quest for undiscovered beauty,
by examining the lives of cells,
starting with the stem cells that reside in each and every person.

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