What is
Exosome?
Exosomes are small vesicles (approximately 30-150 nanometers in diameter) that are secreted by cells and play a crucial role in cell-to-cell communication. They carry a wide range of molecular contents such as proteins, lipids, mRNA, and microRNA (miRNA), which they can transfer to recipient cells, influencing their function and behavior.
Exosomes are minuscule extracellular vesicles, essentially tiny parcels of signaling information, each being a thousandth the size of a cell. They are generated by almost all cell types as a form of intercellular communication, functioning as a natural paracrine signaling mechanism that ensures the smooth operation of a healthy body.
These vesicles are packed with critical components such as growth factors, enzymes, receptors, transcription factors, and matrix proteins, which are essential for cell structure, function, and signaling. Additionally, exosomes carry messenger RNA (mRNA), the template for protein synthesis, and micro RNA (miRNA), a key player in intracellular signaling. Thanks to the membrane they share with their parent cells, exosomes efficiently safeguard their cargo of proteins and miRNA from degradation, ensuring safe delivery to the target cell.
Upon reaching their target cells, exosomes release their contents, which can directly impact intracellular processes and signaling pathways. The exosomal proteins may prompt the target cell to produce new proteins, while the exosomal mRNA gets translated into regenerative proteins. Moreover, the miRNA from exosomes can modulate the protein production in the target cell by suppressing the synthesis of specific endogenous proteins. This signaling not only influences the immediate target cell but can also affect the exosome loading in subsequent cells, creating a ripple effect that has a more lasting and profound impact than the proteins found in Platelet-Rich Plasma (PRP) or amniotic fluid alone.
AD-MSC-CM Exosomes
Acquire adipose tissue and isolate stem cells
Acquire adipose tissue
Adipose-derived
stem cells
Structure of AD-MSC-CM exosomes (TEM image)
- Human Adipose Stromal Cell Conditioned Media : circular structure
- Black line : Human Adipose Stromal Cell Conditioned Media membrane (Lipid bilayer)
How do we secure adipose-derived stem cells
Human Application Test Report
Completion of primary stimulation evaluation test through skin patch for 24 hours of human adipose stem cell-derived exosome mixture (IRB approval)
“Obtain human safety data”
Confirmation of
Agreement for Eligibility
of Donor safety
Confirmation of
Agreement for Test of
Congenital and Chronic Disease
Confirming of
Agreement for Test of TSE
Consent of Agreement
for Adipose tissue
Completed the anti-aging efficacy evaluation test of the human adipose stem cell-derived exosome mixture
For A Total Of 4 Weeks Of Testing, As A Result Of The Test On 13 Study Subjects, The Test Site Using The “AD-MSC-CM Exosomes (1St Agent) & Skin Solvent (2Nd Agent)” Sample Showed Wrinkles Around The Eyes, Skin Moisture, Elasticity, And Pigmentation Compared To Placebo. It Was Confirmed That There Is An Effect Of Improving Density (Anti-Aging Effect), And A Statistically Significant Difference (P < 0.05) Between Groups Was Also Observed In Comparison With The Control Site Using The Control Sample. Therefore, When Judged Comprehensively, It Is Judged That The Test Sample Can Help Skin Anti-Aging.
“Prove anti-aging function in human skin”
Exosome vs Stem cell
The hot Exosome Market
- Mesenchymal stem cells (MSCs) are cells that have ability to differentiate into
other types of cells by external environmental factors. They are known to have
anti-inflammatory, immune-modulating, and regenerative abilities.
- Recent reports have shown that exosomes secreted from MSCs possess most
of the abilities of MSCs and play a major role in various medical therapeutic
effects.
- Exosomes can be combined with existing components or methods to develop
new components and new products, so it is estimated that exosomes will
replace more than 70% of the current stem cell market.
Review Article
- “Exosomes and Their Therapeutic Potentials of Stem Cells paracrine secretion
is extracellular vesicles (EVs), particularly the exosome fraction that mainly
contributes to the action of stem cells in which genetic information can be
horizontally”
- “Skin Brightening Efficacy of Exosomes Derived from Human Adipose Tissue-
Derived Stem/Stromal Cells: A Prospective, Split-Face, Randomized Placebo-
Controlled Study- Exosomes can be combined with existing components or
methods to develop”
- such as messenger RNAs (mRNAs) and microRNAs (miRNAs), and
metabolites [10]. Exosomes derived from MSCs (MSC-exosomes) primarily
mediate the paracrine effects of MSC therapy and are a promising next-
generation cell-free therapeutic option (8,9]. MISC-exosomes have the
potential to
AD-MSC-CM exosomes
functional analysis
Increase Skin Moisture Content
When applied to the skin for 4 weeks,
it is confirmed that the skin moisture content
increases by 20.35%
Increase Skin Elasticity
When applied to the skin for 4 weeks,
skin elasticity increased by 15.12%
Skin Whitening Effect
When applied to the skin for 4 weeks,
Through inhibition of melanin content (6.94%) Confirmation of increased skin whitening effect
Anti-Wrinkle Improvement
Improvement of Skin Density
How to create exosomes.
01
Cell
02
Cell culture
03
Remove large particle
& cell debris, etc
04
Salting out sediment
05
2nd Filteration
(Remove proteins
& salts, etc.)
06
Isolation & Purification
07
Exosome
Important tests before release
Appearance
Confirmed visually.
Identity Test
Qualitative analysis using liquid chromatography.
Purity Test
Test for the absence of nucleic acids from the origin cells and confirmation of the absence of Bovine Serum Albumin (BSA) in the culture medium.
Content Test
Test the total protein content according to the pharmaceutical standards and testing methods using Bradford's Method.
Bacteria/Fungi/Mycoplasma/Virus Testing
Bacteria/Fungi/Mycoplasma negative test - confirmed by negative results without specified criteria. Virus testing is conducted by a contracted organization for verification.
Deviation Handling
In case of inappropriate test results, the cause is investigated, and corrective actions are taken.
In Vivo & In Vitro Test
This combined approach enhances the research process, optimizing both scientific outcomes and ethical considerations.
NTA analysis
Measurement for the particle numbers of exosomes.
Biomarker analysis (Western blot)
To see the amount of exosomes by the volume of tetraspanin protein CD9 & CD63
Efficacy in vivo
Cell Viability (Macrophage)
No cytotoxicity observed up to a 10% concentration.
Cell Viability (Fibroblast)
No cytotoxicity observed up to a 10% concentration.
Wound Healing Assay
No cytotoxicity observed up to a 10% concentration.
Expected to be effective in healing wounds.
Biomarker analysis
(Western Blot)
Tetraspanin proteins : General Exosome Markers (CD9, CD63)
- Associate with adhesion molecules, transmembrane receptors and
intracellular signaling proteins to facilitate and regulate signaling events.
- Have four membrane spanning regions and are localized to tetraspanin
enriched microdomains(TEM) in the plasma membrane.
What’s in our
250 growth factor?
Contains around 250 growth factors
(Promotes cell division or growth and differentiation)
- HGF Hepatocellular Growth Factor :
Efficacy of cell activity induction and surgiçal wound treatment
- VEGF Vascular Endothelial cell Growth Factor :
Cell proliferation and angiogenesis promotion
- a EGF Epithelial cell Growth Factor :
Promotes epithelial cell proliferation and promotes the production of collagen, hyaluronic acid and SOD in fibroblasts
- B-FGF Fibroblast Growth Factor
: Skin dermal regeneration factor which is effective in wound treatment
- EGF Epidermal cell Growth Factor :
Promotes cell turnover by expressing epidermal cell growth signals
- KGF Keratinocyte Growth Factor :
Promoting the growth of keratinocytes
- IGF-1 Insulin-like Growth Factor :
Contains Exosome of regeneration and tissue growth promotion - Exosome only exist 0.1% ratio in stem cell conditioned media - Exosome is nano vesicles of 50-200m size, containing various genetic information substance in cells
Multiplex Human
Cytokine ELISA Analysis
- Overall, AD-MSC-CM showed high expression of most cytokines.
- Remarkably, in the case of Procollagen 1 alpha 1, the AD-MSC-CM Exo exhibited a staggering three-fold increase in comparison to AD-MSC-CM, underscoring the significant potential of AD-MSC-CM Exo in regenerative medicine.
- It is a precursor to the protein collagen, an essential factor in connective tissues.
USC-CM exosomes
Umbilical cord blood is a potent source of vital energy, essential for the regeneration of all body tissues.
Umbilical cord tissue blood contains potent vitality and represents the youngest form of blood available. It is crucial in treating blood-related diseases such as leukemia and other cancers. Furthermore, it plays a vital role in the development of treatments for various intractable diseases through the use of stem cells derived from umbilical cord blood.
Umbilical Cord
Blood Stem Cell
UCB stem cells are the youngest cells excellent at suppressing, regulating, & repairing autoimmune diseases.
Embryo
Blastocyst
Fetus
Newborn
Adult
Human cord blood cell conditioned media contains 14 times more of exosomes and highly concentrated active ingredients for powerful cell regeneration and immunity control
Human cord blood cell CM
- Active ingredients, abt 4.5X
- Efficacy 5X
Human cord blood cell
exosome
- Active ingredients, abt 3 X
- The smallest & even size
(1/1700 of pores )
USC-CM exosome Technology
Stem Cell Isolation
95%
High isolation purity
95+% purity of stem cell isolation
80%
Highly efficient isolation
8 out of 10 umbilical cord, stem cell isolation
Extended isolation time
Stem cell separation within 72 hrs → secured supply
Mass Culturing Of Stem Cell
240ea/unit (appx. 1 trillion) culture possible
Day 01
100x
Day 02
40x
Day 03
40x
Day 04
40x
Day 05
40x
A Single Unit Of Cord
300+ patients can be treated
Pharmaceutical Level
of Quality Control
Core Competency -
Skin Regeneration Effect
Proven effect of skin regeneration
by collagen I&III increase
Collagen1A1
Collagen3A1
Rejuvenating protein 11
‘Nature’, ‘Cell’, ‘Science’introduce rejuvenating protein 11
Open Med. 2017; 12: 376-383
DE GRUYTER
Review article
Massimo Conese*, Annalucia Carbore, Elisa Beccia, Antonella Angiolillo
The Fountain of Youth: A tale of parabiosis, stem cells, and rejuvenation
ation. Eventually, further studies have brought to identify some soluble factors in part responsible for these rejuvenating effects, including the chemokine CCL11, the growth differentiation factor 11, a member of the TGF-B superfamily, and oxytocin. The question about giving whole blood or specific factors in helping rejuvenation is open, as well as the mechanisms of action of these factors, deserving further studies to be translated into the life of (old) human beings.
Restoring systemic protein 11 levels reverses age-related dysfunction in
mouse skeletal muscle.
Science. 2014 May 9;344(6184):649-52.
Growth differentiation factor 11 is a circulating factor that reverses
age-related cardiac hypertrophy.
2013 May 9;153(4):828-39
Protein 11 modulates NGN3+ islet progenitor cell number and promotes
beta-cell differentiation in pancreas development.
Vascular and neurogenic rejuvenation of the aging mouse brain
by young systemic factors.
Protein 11
Protein 11 induces skin cell proliferation & skin protein synthesis that leads to skin rejuvenation.
* Protein 11(Growth differentiation factor 11)?
The ‘key rejuvenation’ growth factor stimulates the synthesis of collagen
and elastin in fibroblasts, which aids in skin regeneration and lifting.
Ingredient of
enhancing skin immunity
Skin trouble caused by reduced immunity, is recovered with
26 anti-inflammatory ingredients
Ingredient of activating
hair loss prevention
28 active ingredients for hair loss prevention to induce healthy scalp environment
Milk Exosomes
Milk-Exo
INCI Name : Milk Exosomes
Effectiveness : Anti-inflammatory, Whitening, Antioxidant
Introduction
Milk-Exo: A Comprehensive Nutrient Source
- Rich in 114 nutrients: carbohydrates, proteins, fats, calcium, and minerals.
- Historical beauty uses: Cleopatra’s milk baths and Poppaea Sabina’s milk face
washes.
- Benefits for skin: balances moisture and oil, hydrates, exfoliates (AHA),
and whitens (niacinamide).
Exosome Analysis
Result (sizes in nm)
Concentration : 8.1 E+7 Particles / mL
Dilution Factor : 10000
Original Concentration : 8.1 E+11 Particles / mL
High-purity exosomes were directly isolated and purified from milk. According to the Nano Particle Tracking Analysis (NTA), the particle size is approximately 136.2 nm.
Efficacy in vitro
Human Application Test Report
Confirmation of exosome absorption into cells through PKH26 staining
Anti-inflammatory activity
Antioxidant activity
Plant Exosomes
Plant-Derived Exosome
Plant-Exosome
Plant derived extracellular vesicles materials development
What is plant-derived
exosome
It is produced in the multivesicular body (MVB) within the cytoplasm and secreted into the apoplast, the space between the cell membrane and the cell wall. This process is involved in plant defense against pathogens, cell wall construction, and intercellular communication. Temporarily, cell wall remodeling enzymes are secreted to pass through the cell wall, and these enzymes have been discovered in exosomes Ref. Eric Woith., et al., Extracellular vesicles-Connecting kingdoms., Int. J. Mol. Sci., 2019, 2, 5695.
[Plant-derived exosome formation process]
Ref. Eric Woith, et al., Plant Extracellular Vesicles and Nanovesicles:
Focus on Secondary Metabolites, Proteins and Lipids with Perspectives on
Their Potential and Sources., Int. J. Mol. Sci., 2021, 22(7), 3719.
[Plant-derived exosome components]
Ref. Mariaevelina Alfieri., et al. Plant-Derived Nano and Microvesicles for Human Health and
Therapeutic Potential in Nanomedicine., Pharmaceutics., 2021, 13(4), 498.
Plant-derived exosomes are secreted into the apoplast, which is a free space formed by the cell membrane and cell wall in plants, playing a crucial role in the movement of nutrients and water. These exosomes can be visualized using electron microscopy (TEM), providing detailed images of their structure.
Ref. Linda Palmer, Plant Cells Shed Membrane-Bound Bubbles that Are Packed with Tiny RNA Molecules.,
The plant cell, 2019
Physiological functions
of plant-derived exosomes
Ref. Lanlan Yu, et al., Plant-Derived Nanovesicles: A Novel Form of Nanomedicine., Front.
Bioeng. Biotechnol., 2020., 8:584391.
Ref. Sophie Rome., Biological properties of plant-derived extracellular vesicles., Food Funct.,
2019,10(2):529-538.
Plant-derived exosomes exhibit a variety of functions, including promoting cell proliferation, regulating inflammation, exerting anticancer and antioxidant effects, modulating the immune system, aiding tissue regeneration, and managing intestinal flora. Notably, these exosomes can serve as drug carriers without causing side effects, and they are currently the focus of numerous studies.
Plant-specific,
lipid composition and function
Ref. THE CELL, Fourth Edition, Figure 13.2
1. Grapes 1) Phosphatidic Acid (PA) : Acts as a cell proliferation and survival signal via the mTOR pathway. Involved in cell transformation, tumor progression, and differentiation.
2. Grapefruit 1) Phosphatidylethanolamine : Abundant in the mitochondrial inner membrane, plays roles in membrane fusion and contractile functions during cytoplasmic division. 2) Phosphatidylcholine : The most common phospholipid in lipids and mammalian membranes, essential for forming a strong bilayer and necessary for normal cell cycle progression.
3. Sunflower Seeds 1) Phosphatidylinositol : Located on the cytoplasmic side of the plasma membrane, it plays a role in creating and maintaining polarized membrane domains.
4. Ginger 1) Digalactosyldiacylglycerol (DGDG) : Involved in thylakoid production during chloroplast biogenesis in plants, with antioxidant and anti-inflammatory effects on Caco-2 (colon cancer cell line) cells. 2) Monogalactosyl Monoacyl Glycerol (MGDG) : Exhibits anti-inflammatory activity in cultured articular chondrocytes, prevents cell proliferation without affecting cell
5. Shogaol Anti-cancer, antioxidant, antibacterial, anti-inflammatory and anti-allergic effect
Ref. Sophie Rome., Biological properties of plant-derived extracellular vesicles., Food Funct.,
2019,10(2):529-538.
Role and Advantages
of Plant-Exosome
Role of Plant-Exosome
Pathway targeting
siRNA or
mRNA delivery
Drug delivery
Ref. Mariaevelina Alfieri, et al., Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine., Pharmaceutics 2021, 13(4), 498.
Advantages of Plant-Exosome
- Capable of crossing cell membranes and having biocompatibility
with mammalian cells.
- Compared to synthetic nanomaterials, it does not induce an immune or inflammatory response in normal host cells.
- Does not cause toxicity, immunogenicity, or allergy problems.
- Can deliver anticancer or antioxidant factors to tumor cells, acting as carriers.
Comparison of
plant and animal-derived
exosomes
Plant Exosomes
Plant cell derived Exosome
Ref. Mariaevelina Alfieri., Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine., Pharmaceutics 2021, 13(4), 498
- Components within a large category such as
mRNA, miRNA, Proteins, and Lipid are similar.
- However, there is a difference in the number of
lipid components and proteins in detail.
- Plant-derived exosomes :
Lipid composition and high amount (compared to animal cells)
- Animal-derived exosomes :
Contains a large amount of protein component and quantity
There is a difference in the composition of lipids according to each plant and the functions acting on animal cells, so that the physiological activity effect of the lipid is higher than the protein component in the plant exosome.
Lactobiome Exosomes
LactoBiome-Exo
INCI Name : Lactobacillus Ferment,Butylene Glycol, 1,2-Hexanediol
Effectiveness :
(Anti-inflammatory)
- Exosomes contain microRNAs and cytokines that significantly reduce inflammation, making them effective in treating acne and other inflammatory skin conditions.
(Anti-inflammatory)
- Exosomes contain microRNAs and cytokines that significantly reduce inflammation, making them effective in treating acne and other inflammatory skin conditions.
Introduction
Lactobiome Exosomes
Antioxidant Effect
Anti-Wrinkle Effect
LactoBiome Exosome Particles
According to the Nanoparticle Tracking Analysis (NTA) results, exosome particles of approximately 99.1 nm in size from LactoBiome-Exo were confirmed.
Efficacy of
LactoBiome-Exo_in vitro
Studies
Before & After
# Acne / Trouble Alleviation
# Acne / Trouble Alleviation
# Acne / Trouble Alleviation
# Acne / Trouble Alleviation
Melanin Reduction
Pore minimizing & Tightening
Extreme Dryness Improvement
Skin Brightness
Skin Elasticity, Brightness
Fine Lines, Wrinkles Reduced, Smoother Skin
New Hair
New Hair
New Hair
New Hair
New Hair
New Hair
New Hair
New Hair
Question And
Answer
Contact
Ask for Distributorship or
Contract Manufacturing Business
