What are stem cell exosomes?

Microscopic vesicles called "exosomes" exist both inside and outside stem cells. Exosomes were discovered in 1983, and research into them has progressed in the field of life science,
suggesting their connection to various physiological functions and the onset of pathologies. In the medical field, they have already been linked to new diagnostic methods using bodily fluids, and
there are high hopes for their future use in regenerative medicine.

Mechanism of exosomes

Inside exosomes are short gene sequences called microRNAs. Direct information is written in microRNA, and it is said that this information is the effect of stem cells. A study at UC Sandiego University reported that "stem cells have similar pharmacological effects even if they are enucleated," which means that the main pharmacological action of stem cells is EVs such as exosomes. . In addition, exosomes are naturally derived from cells, are already present in large numbers in the human body, are said to have low side effects, and are being recognized for their superiority compared to cell therapy.

Flow of exosomes created at our hospital

Note: Exosomes have traditionally been nearly invisible, so they are photographed by shining a laser on them and reflecting it, making them visible. The intensity of the reflection depends on the size of the particle and the angle of reflection.
In 1996, it was discovered that exosomes have the function of transporting substances to other cells. Furthermore, in 2007, it was revealed that exosomes contain large amounts of genetic transcription information (hereinafter referred to as microRNA), and that exosomes function as a messaging tool for intercellular communication.

MSC exosome treatment

Citation: Venkat P, Chopp M, Chen J. (2018) Cell-Based and Exosome Therapy in Diabetic Stroke. Stem Cells Transl Med


numerous papers have demonstrated that exosomes derived from mesenchymal stem cells (MSCs) are important in the mechanism of MSC cell therapy

The advantages of stem cell therapy include clear safety and efficacy risks, well-established legal regulations, and a clear path to clinical
trials

Comparing exosomes to stem cell therapy

・Exosomes themselves are separated and purified cell secretory components, so there is no risk that the local condition of the administered cells will affect the therapeutic effect, as is the case with cell therapy.
・Because they are smaller than cells, the possibility of embolism is theoretically low.
・They have good migration to target tissues.
・Compared to cell therapy, multiple administrations are possible.
・Exosomes are easy to quantify (particle number).

・A larger number of cells than is required for cell administration is required.
・Quality control and manufacturing management have not yet been standardized.

The 2019 ISEV journal, Journal of Extracellular Vesicles, defines therapies involving MSC-derived exosomes [6,7,8]. However, the standards and characterization of MSC exosomes for therapeutic purposes at our hospital conform to the methods proposed by the Japanese Society for Regenerative Medicine.
See: An example of exosome manufacturing management (Japanese Society for Regenerative Medicine).

*How to prepare and treat exosomes (Japanese Society for Regenerative Medicine 2021/3/10)

(1) Disclosure that it is an unapproved drug: This drug is not approved in Japan and will be prescribed at your own expense.
*Public relief systems (Drug Adverse Reaction Relief System, Biological Product Infection Relief System) do not apply to unapproved drugs.
(2) Disclosure of acquisition route, etc.: This drug is formulated in-house.
(3) Availability of domestically approved drugs with the same ingredients and efficacy: None.
(4) Disclosure of information regarding safety in other countries: Based on the safety standards for exosome therapy. No major adverse events have been reported.

  1. Allan D, Tieu A, Lalu M, Burger D. Mesenchymal stromal cell-derived extracellular vesicles for regenerative therapy and immune modulation: Progress and challenges toward clinical application. Stem Cells Transl Med 2020; 9(1):39-46.
  2. Rohde E, Pachler K, Gimona M. Manufacturing and characterization of extracellular vesicles from umbilical cord-derived mesenchymal stromal cells for clinical testing. Cytotherapy 2019; 21(6):581-592.
  3. Witwer KW, Van Balkom BWM, Bruno S, Choo A, Dominici M, Gimona M, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles 2019; 8(1):1609206
  4. Elahi FM, Farwell DG, Nolta JA, Anderson JD. Preclinical translation of exosomes derived from mesenchymal stem/stromal cells. Stem Cells 2020; 38(1):15-21.
  5. Tsuchiya A, Takeuchi S, Watanabe T, Yoshida T, Nojiri S, Ogawa M, et al. Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration. Inflamm Regen 2019; 39:18 .

 

  1. Lener T, Gimona M, Aigner L, Borger V, Buzas E, Camussi G, et al. Applying extracellular vesicles based therapeutics in clinical trials -an ISEV position paper. J Extracell Vesicles 2015; 4:30087.
  2. Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018; 7(1):1535750.
  3. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-317



Exsm Clinical Trial for DM

NCT03106246

Circulating Extracellular Vesicles Released by Human Islets of Langerhans

McGill University Health Center

CHU de Quebec-Universite Laval

NCT03660683

Effect of Saxagliptin and Dapagliflozin on Endothelial Progenitor Cell in Patients With Type 2 Diabetes Mellitus

Sabyasachi Sen|George

Washington University

NCT03250078

A Pancreatic Cancer Screening Study in High Risk Individuals Including Those With New-Onset Diabetes Mellitus

Western Connecticut Health 

Network

NCT02649465

SGLT2 Inhibitor Versus Sulfonylurea on Type 2 Diabetes With NAFLD

Kanazawa University

Kowa Company, Ltd.

NCT02138331

Effect of Microvesicles and Exosomes Therapy on Hui-cell Mass in Type I Diabetes Mellitus (T1DM)

General Committee of Teaching Hospitals and Institutes, Egypt

NCT03027726

Prevention of Diabetes in Overweight/Obese Preadolescent Children

Basque Country University

Ministerio de Competitividad, Spain

NCT03392441

Insulin Deprivation on Brain Structure and Function in Humans With Type 1 Diabetes

Mayo Clinic

 

Exsom Clinical Trial for Obesity

NCT03459703

Effect of Time-Restricted Feeding on Fat Loss and Cardiometabolic Risk Factors in Overweight Adults

University of Alabama at Birmingham

NCT03762629

Exercise and Diet Restriction on Cardiovascular Function in Obese Children and Adolescents

Guangzhou Sport University



What is the difference between exosomes and cell supernatant?

Exosomes are small particles less than 100 nm in size extracted from culture supernatant by further centrifuging. Our hospital uses an advanced centrifuge called the Beckman Coulter Optima XE.
Nano Sight explanation: https://youtu.be/TuFVmSb7NvM

Exosomes and culture supernatant produced at our hospital were measured using NanoSight, and the graph shows the cell diameter (horizontal axis) and particle number (vertical axis). Left: Exosomes,
Right: Culture supernatant . The peak (steep mountain) around 100 nm is exosomes.
Exosomes are detected in both, but the culture supernatant also has peaks at 300 nm and 800 nm, which are MVs (microvesicles), particles with different functions from exosomes. Incidentally, stem cells are about 100 μm in diameter,
with a radius 1,000 times that of exosomes. This means that culture supernatant contains many MVs other than exosomes, and has a different composition from pure exosomes.
Mesenchymal Stem Cells and Exosome Therapy: https://youtu.be/YnCQZ6DWLN4

Our hospital has consistently used non-animal culture media (animal-free) since the beginning.
» Learn more
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Picture of the tissue right after collection.
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They are stored in special tanks filled with liquid nitrogen at minus 196 degrees Celsius,
allowing for long-term storage.
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We conduct bacteriological tests and virus inspections to confirm safety. And the number of stem cell is calculated by measuring surface antigen markers.
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Our stem cells are based on collection criteria, preservation management standards, hygiene management standards, quality control standards, and the doctor conducts checks of bacteria examination, etc.
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We use cell counter to counts the number of cells.
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Doctor Takaaki Matsuoka
Graduated from Keio University School of Medicine in 2003, and

worked in the Department of Anesthesiology at Keio University Hospital. In 2004, he joined
Keiyukai Keiyu Hospital in the Department of Anesthesiology and Intensive Care Unit. In 2005, he joined the Shobikai Medical Corporation. In 2009, he served as the Vice President of the Shobikai Medical Corporation.
In 2013, he founded Rene Clinic in Omotesando
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He is a member of the PGA at Harvard Medical School.
・Peking University Executive MBA
・Specialist of the Japanese Society of Aesthetic Plastic
Surgery ・Ministry of Health, Labor and Welfare Certified Anesthesiologist
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Doctor Toichi Tonozaki
Graduated from Asahikawa Medical University
April 2008 Joined Showa University Plastic Surgery Department
January 2010 Chiba Prefecture Emergency Medical Center Plastic Surgery Department
April 2014 Director of Komuro Cosmetic Surgery Tokyo Clinic
January 2015 Director of a major cosmetic surgery dermatology clinic
October 2015 Omotesando Helene Clinic
<Affiliated societies, etc.>
Specialist of the Japanese Society of Plastic Surgery
Full member of the Japanese Society of Aesthetic Plastic Surgery (JSAPS) Full member of the Japanese Society of Aesthetic Plastic Surgery
(JSAS) Full member of the Japanese
Society of Wound Surgery
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Miki Matsuoka, Dentist
March 2004 Graduated from Iwate Medical University School of Dentistry
2005-2006 Worked at Tohoku University Hospital
2006-2009 Worked at a medical corporation in Tokyo
2010-2014 Worked at a medical corporation in Kanagawa Prefecture
2015 Opened Meguro Honmachi Dental Clinic
March 2018 Opened Meguro Honmachi Sakura Dental Clinic (branch)
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Katsuya Ozawa
1995: Researcher at RIKEN (glycolipid research)
2003: Researcher at Meiji Pharmaceutical University (diabetes and hematopoietic stem cell research)
2012: Institute of Medical Science, University of Tokyo Hospital
　　　Stem cell bank technician (iPS cell/ES cell research)
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Daichi Kasai
Graduated from Tokyo University of Agriculture and Technology in 2014.
Graduated from Keele University School of Medicine with a Master's degree in Cell and Tissue Engineering in 2016.
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Stem Cell Academic Advisor Inoko Hidetoshi,
Professor Emeritus, Tokai University (Molecular Life Sciences)
1970: Graduated from
the Faculty of Science, Kyoto University 1975: Completed doctoral studies at the Kyoto University Institute for Virus Research Graduate School
1988: Visiting Researcher, Royal Cancer Institute, UK
1992: Professor, Department of Molecular Biochemistry, Tokai University School of Medicine
2001: President, Japanese Society for Histocompatibility Research (until 2005)
2006: Dean, Tokai University School of Medicine (until 2010)
Currently Professor Emeritus, Tokai University
Involved in organ transplants and cell transplants, Inoko Hidetoshi provides guidance on transplant immunology, which is important for stem cell transplants at our hospital.
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Doctor Onodera Gokei
Graduated from Wakayama Medical University in 2006.
Joined Showa University's Plastic Surgery Department in 2008.
Became an assistant professor of Showa University's Plastic
Surgery Department in 2013-2014. Became an assistant professor of Showa University's Plastic Surgery Department in 2015. Became a member of a major cosmetic surgery
clinic in 2016. Became a member of the Advanced Medical Group Group.
<Affiliated Academic Societies>
Qualifications: Plastic Surgery Specialist.
Affiliated Academic Societies: Full member of the Japanese Society of Craniofacial Surgery.
Registered doctor in the JAAS.
General surgery, cosmetic surgery, and cosmetic dermatology.
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culture video
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Doctor [Internal Medicine] Kosuke Iguchi

・Certified internist by the Japanese Society of Internal Medicine
・Specialist physician of the Japanese Circulation Society

1996 Graduated from the School of Medicine, University of Occupational
and Environmental Health, University of Occupational and Environmental Health Hospital
1998 National Hospital Organization Kyushu Medical Center
2001 Kyushu University Hospital
2009 Fukuoka Sanno Hospital
2018 Fukuoka Varicose Vein Clinic opened
2019 Omotesando Helene Clinic

<Affiliated academic societies, etc.>
・Japanese Society of Cardiovascular Interventional Therapy
・Japanese Vascular Society

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Former Health, Labor and Welfare Minister Ritsuo Hosokawa

Minister
of Health, Labor and Welfare,
Former Member of the House of Representatives (7 terms)
, Attorney, Director of Koshigaya General Law Office,
Standing Advisor to the Democratic Party of Japan Saitama Prefectural Federation

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