January 7, 2021

Research field: life science and medicine; Keywords: sweat glands, anatomy, three-dimensional
structure, heat stroke, hyperhidrosis, antiperspirant, regenerative medicine
Successfully visualized in joint research by Mandom Corporation andGraduate School of Pharmaceutical Sciences, Osaka University

Newly revealed three-dimensional structures of human sweat glands
shown in Gray’s Anatomy, the gold standard anatomy textbook―Expectations on the development of better diagnostic measures and treatments for heat stroke andhyperhidrosis and application to sweat gland tissue regeneration -Gist of the research The newly uncovered human sweat gland structures--spatial cell shapes and arrangements ofsweat gland and blood vessels facilitating sweat secretion--successfully visualized byour joint research team and published in June 2017 are included in the latest edition ofGray’s Anatomy.
Gray’s Anatomy is considered globally to be the gold standard textbook on anatomy.

Our research findings shared through thistextbook may contribute to a better understandingof sweat gland functions and therefore to thedevelopment of more effective diagnostic measuresand treatments for sweating disorders, such ashyperhidrosis (excessive sweating) and heatstroke, and regeneration of sweat gland tissues.

Overview
Three-dimensional (3D) structures of human sweat glands
have been successfully visualized by a joint research teamof Guest Professor Fumihiro Okada at Laboratory of Advanced
CosmeticScience ※ 1,

PharmaceuticalGraduate

Science,

Osaka

SchoolandUniversity;

SchoolofProfessor

Kiyotoshi Sekiguchi at Division of Matrixome Research andApplication,
University;

InstituteandforAssistantProtein
Professor

Research,
AtsushiOsaka

Tanemura,

Associate Professor Hiroyuki Murota (currently professor atFigure 1
Gray’s Anatomy（42nd edition）Nagasaki University Graduate School of Biomedical Sciences),and Professor Emeritus Ichiro Katayama at Graduate School of Medicine, Osaka University. Please visit
the portal site for research at Osaka University, ResOU, for more details (as of June 22, 2017;https://resou.osaka-u.ac.jp/en/research/2017/20170622_3). The fruit of the research is included inthe latest 42nd edition of Gray’s Anatomy※2,
the global gold standard textbook on anatomy.

During the 13th century, human anatomy
was acknowledged as essential in medical
education to promote the understanding of
the body function and structure, and thisareaofcontributed

sciencetohassinceadvancement

ingreatly
modernmedicine, including diagnosis and surgicaltreatment.

The

first1858

editionofGray’s Anatomy is said to be published tohelp medical students study human anatomy
in dissection training. Over more than 160
years since its first publication, thisbook remains to be regarded by many as themost prestigious anatomy book and a great
textbook for learners and thus read by many
people in the medical field and students
aspiring to become doctors or anatomists.
The newly visualized detailed structures
ofhumansweat

arrangement

offacilitate

theglands
bloodsweat

andspatialvessels

secretion

thatoftheFigure 2
Three-dimensional structure of human sweat glands
with blood vessels

glands are contained in the ‘skin’ partin Section 1 of the latest edition of Gray’s Anatomy (consisting of seven sections; October2020) at the request of its publisher.
The fruit of this research may help us deepen our understanding of sweat gland structures andthereby may be useful for the development of next-generation antiperspirants and also for further
clarification of mechanisms of and advancement in treatment for heat stroke and hyperhidrosis.
We filed for a patent application for these research outcomes and have reported on theirutility at Gordon Research Conference※3 and other occasions.

Background of the researchWith advancing global warming, despite our increasing efforts to prevent occurrence of heatstroke, many heat stroke patients are taken by ambulance to hospitals every summer in Japan,
which is one of our social issues. Sufficient knowledge of the structures of sweat glands, which
contract in sweating, is essential to improve impaired sweating function. Conventional analysis
methods, however, were not good enough to clarify the complicated structures of the sweat glands.
Our research group then succeeded, using whole-mount staining, in visualizing the 3D structuresof human sweat glands and uncovering their characteristic structural features, which indicatedthat human sweat glands had unique secretory mechanisms for sweat excretion.

Research content
Gray's Anatomy shows the three-dimensional structure of the human sweat glands that werevisualized by our research group.
Sweat gland is tubular exocrine gland consisting of the secretory portion and the duct. The
gland forms the complex coiled structure that compose secretory portion and part of the duct indeep dermis. The secretory portion in the coiled region generates sweat that is released to theskin surface through the duct. Several lines proposed that contraction of the secretory portion
induce the sweating. To better understand the anatomical structure of sweat gland, the detailsof the three-dimensional (3D) coiled structures of sweat glands were visualized using a wholemount staining method. 3D coiled gland structures demonstrated that the ducts and secretory
portions were comprised of distinct tubular structures. Ductal tubules were occasionally bent,
while secretory tubules were frequently bent and formed a self-entangled coiled structure likea towel being squeezed. 3D visualization of the glands also revealed the spatial arrangement ofblood vessels facilitating sweat secretion. The blood vessels were situated adjacent to not only
the ducts, but also the secretory portions of sweat glands, suggesting that blood vessels runningalong sweat gland tubules are involved in the supply and reabsorption of sweat.

Social impact of the inclusion of our research results in Gray’s Anatomy
Our joint research findings introduced in the gold standard anatomy textbook Gray’s Anatomy
may serve as the basis of new ideas for elucidating sweat gland disorders, leading to better
understanding of basic mechanisms of sweat gland contraction and homeostasis maintenance, which
may then result in clarification of and novel treatments for sweating related disorders (such asheat stroke and hyperhidrosis), and potentially development of next-generation antiperspirantsthat directly inhibit sweat gland contraction to suppress sweating and sweat gland regenerativetechnologies.

Special notes
The images shown in Gray’s Anatomy are those analyzed using the methods described in our reportthat appeared in the US scientific journal PLOS ONE (online).
Title：“Three-dimensional Cell Shapes and Arrangements in Human Sweat Glands as Revealed byWhole-mount Immunostaining”
Author：Ryuichiro Kurata1, 2, 3*, Sugiko Futaki3, Itsuko Nakano3, Fumitaka Fujita1, 2, Atsushi Tanemura4,Hiroyuki Murota4, Ichiro Katayama4, Fumihiro Okada1, 2, and Kiyotoshi Sekiguchi3,**
Our research achievements, visualization method of the three-dimensional structure of the sweat
gland, is registered as a patent.
Title of Invention: THE CONFIRMATION METHOD OF THE SWEAT GLANDS
Patent Number：6555973
Inventors： Ryuichiro Kurata 1, 2, 3 , Fumitaka Fujita 1,2 ,Sugiko Futaki 3, Kiyotoshi Sekiguchi 3 ,Atsushi Tanemura4 , Hiroyuki Murota 4 ,Ichiro Katayama4*First author**Corresponding author
1Laboratory of Advanced Cosmetic Science, Graduate School and School of Pharmaceutical Science,Osaka University

234Mandom Corporation, Foundational Research LaboratoryOsaka University, Protein Research Institute, Research Department
Osaka University, Graduate School of Medicine, Dermatology Department of Integrated Medicine

This research was partly supported by Grants-in-Aid for Scientific Research from the Japan
Society for the Promotion of Science (16K19721: Analysis of three-dimensional structure of humansweat glands, 18K16028: Analysis of thermoregulatory disorders using three-dimensional tissue
models generated from human sweat gland stem cells, and 20K08650: Establishment of the humansweat gland organoids for the improvement of heat stroke)

Glossaries※1 Laboratory of Advanced Cosmetic Science
The Laboratory of Advanced Cosmetic Science is a research laboratory established jointly by theGraduate School and School of Pharmaceutical Science, Osaka University and Mandom Corporationin June 2015. Joint research laboratories receive investments from private companies and otherorganizations. Researchers from the university and the investing company conduct research on
the same theme on an equal footing, with the aim of achieving breakthrough research results.
The Laboratory of Advanced Cosmetic Science is an independent research organization in OsakaUniversity. The university and Mandom Corporation cooperate to conduct research flexibly andrapidly while exchanging information and creating knowledge.
※2 Gray's Anatomy (42nd edition)
Gray's Anatomy (42nd edition)- Anatomical Basis of Clinical Practice
Author: S.Standring
Publisher: ELSEVIER, LONDON
ISBN: 978-0-7020-7705-0
Total Pages: 1588pp.
Published Date: October 2020
※3 Gordon research conference
2019 Gordon research conference (Epithelial Differentiation and Keratinization)
Date: July 7 - 12, 2019

Venue：Jordan Hotel at Sunday River (Maine, USA)
Title: Isolation and characterization of sweat gland stem cells from human skin
Gordon research conference…One of the historic and prestigious scientific conferences

Inquiries<About the research contents>
Guest Professor Fumihiro Okada
Laboratory of Advanced Cosmetic Science, Graduate School of PharmaceuticalSciences, Osaka University
TEL：06-6105-5792 FAX: 06-6105-5790
E-mail: okada-f@phs.osaka-u.ac.jp

Professor Kiyotoshi Sekiguchi
Department of Contribution Research, Institute for Protein Research, Osaka University
TEL: 06-6105-5935 FAX: 06-6105-5936
E-mail: sekiguch@protein.osaka-u.ac.jp<About this news release>
General Affairs Division, Graduate School of Pharmaceutical Sciences, Osaka University
TEL:06-6879-8144 FAX:06-6879-8154
E-mail: yakugaku-syomu@office.osaka-u.ac.jp
Miyu Sato / Okuda / Kuriyama , Osaka Head Office
Department of Public Relations, Mandom Corporation
TEL: 06-6767-5021 FAX: 06-6767-5045
E-mail: press@mandom.com
Message from the research representative (Ryuichiro Kurata)
Environmental changes forced our early ancestors to travel long distance in search of foodand water, requiring them to opt to lose their fur and have hairless bodies to control bodytemperature

bysweating

throughsweat

glands.

Humansaretheonlyanimalwith

thisthermoregulatory mechanism. On the other hand, because our sweat gland system has not evolved
enough to counter changes in our life styles or aging, these factors tend to affect our sweating,making sweating related disorders (heat stroke, hyperhidrosis) social issues, while data on
human sweat glands, which are important in the treatment of sweating disorders, have been
available only in a limited amount. We believe that continuing accumulation of outcomes of basic
research on human sweat glands will lead to further new findings and advancement in relevant
technologies, and then practical applications in some years’ time.
We started our joint research in 2009, including an isolation method for human sweat glandcells and identification of human sweat gland stem cells, regeneration of an artificial humansweat gland organ, 3D structural analysis of sweat glands, monitoring of contracting motilityof sweat glands, and establishment of immortalized sweat gland cells. It is our intention tocontinue to pursue our research to enable our under-evolved sweat glands to play their roles in
the present social environment.