What Are the Different Sources of Exosomes? Animal and Plant Extraction Methods Are Completely Different

What Are the Different Sources of Exosomes?

Following the official enactment of Taiwan's Regenerative Medicine Dual Laws, cell derivatives (i.e., exosomes) have entered a new era of "standardized manufacturing." Exosomes have become a focal technology in medical and cosmetic fields due to their diverse application potential. 
However, the "source" of exosomes directly affects product positioning, regulatory status, safety, and final application potential. TFDA and ISEV have established clear definitions and application suggestions for different sources. 

Exosomes are essentially "communication vesicles" secreted by cells, measuring approximately 30 –150 nanometers (nm). In academic classification, such vesicles (including exosomes, microvesicles, and apoptotic bodies) are collectively known as "Extracellular Vesicles (EVs)." Additionally, based on their source, they are further categorized into four major types:

1.  Human-derived EVs

˙Source: Primarily from human mesenchymal stem cells (MSCs) sourced from fat, umbilical cord, bone marrow, or amniotic fluid, etc.

˙Characteristics: Highest biocompatibility with the human body and possess specific receptors that create a "homing effect." They contain multiple regeneration and repair factors with potential in tissue repair and anti-inflammation.

˙Regulatory Focus: International INCI registration is mandatory. Effective March 2024, the Taiwan Food and Drug Administration (TFDA) has implemented a case-by-case review framework for human-derived exosome cosmetic raw materials. Such reviews require the submission of comprehensive safety documentation, including but not limited to donor eligibility and screening qualifications, stability study data, and certification of the manufacturing site. Materials approved under this framework are strictly limited to cosmetic use.

2.  Animal-derived EVs

˙Source: Commonly from cow's milk or animal mesenchymal stem cells.

˙Characteristics: Sourcing is relatively easy, and they maintain some biological activity despite cross-species application. 

˙Challenges: Cross species immunogenicity is the biggest challenge, along with the need for strict management regarding zoonotic diseases (e.g., foot-and-mouth disease, mad cow disease). Clinical safety requirements are often more complex than human-derived sources.

3.    Plant derived EVs

˙Source: Plants such as Centella asiatica, ginseng, bitter melon, ginger, citrus, or grapes. 

˙Characteristics: High safety with no risk of animal-related viruses. They contain plant-specific secondary metabolites (e.g., polyphenols, flavonoids) and offer antioxidant and soothing capabilities. 

˙Regulatory Focus: These materials are commonly referred to as “plant exosomes”; however, the scientifically accurate designation is “plant-derived extracellular vesicles.” At present, they are regulated under a flexible management approach applicable to botanical extracts and have been widely adopted by leading international beauty brands as an alternative option.

4.    Synthetic/Biomimetic Vesicles

˙Source: Artificially manufactured via chemical or physical techniques.

˙Characteristics: Uniform specifications and can be embedded with specific drugs or factors. 

˙Disadvantages: Lack the comprehensive nourishment signals of natural cells; their biological activity is often lower than "native exosomes" and they serve better as drug carriers for new drug development. 

Comparison Table of Exosome Sources

What Are the Exosome Extraction Technologies?

Extraction technology determines the purity and biological activity of exosomes. ISEV suggests methods should preserve vesicle integrity as much as possible. Common technologies include:

˙Ultracentrifugation: Uses ultra-high speeds (≧100,000g) for separation. While suitable for laboratory scale research, it can damage the vesicle membrane and lead to protein contamination. 
˙Size Exclusion Chromatography (SEC): Separates based on size. It is gentle and preserves morphology but is difficult to scale for industrial production due to high costs and buffer dilution. 
˙Tangential Flow Filtration (TFF): Separates via fluid parallel to a membrane. Ideal for mass production (≧10L) as it simultaneously concentrates and washes. This closed system meets sterile production needs and fits the industry standard. 
˙Polymer Precipitation: Uses chemical agents (e.g., PEG) to precipitate exosomes. While fast and simple, it leaves polymer impurities and is not recommended for clinical or high-end products.

Key Advantages of Exosomes

˙Nanoscale Penetration: Their diameter is approximately one thousandth (nm level) of a cell (µm level), allowing them to penetrate the skin barrier to the dermis or even cross the Blood-Brain Barrier (BBB). 
˙High Safety: Lacking a nucleus, they cannot mutate or replicate, making tumor risk extremely low compared to cell-based therapy. They also have low immunogenicity risk. 
˙High Stability: Unlike live cells requiring -196°C, exosomes are way more flexible in storage. Moreover, Gwo Xi uses "lyophilization technology" to store exosomes as stable powders at room temperature or 4°C while maintaining bioactivity upon reconstitution.

Exosome CDMO Recommendation | Gwo Xi Stem Cell

Gwo Xi Stem Cell offers one-stop CDMO services compliant with international standards, covering everything from raw material sourcing to application development.
Technical Highlights:
˙Human MSC sources and processes validated by clinical trials. 
˙Human MSC sources hold USFDA DMF registration. 
˙To supply high quality raw materials, including human MSC-derived exosomes and plant-derived EVs. 
˙Collaborations with medical centers for research on degenerative diseases and tissue repair. 
˙Extensive CDMO experience with global aesthetic brands and pharmaceutical companies. 
Gwo Xi Stem Cell follows current ISEV guidance and TFDA regulatory standards to ensure long term product competitiveness. If you have questions about CDMO services or TFDA procedures, please contact us.

References

˙Théry, C., et al. (2018). Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles. Journal of extracellular vesicles, 7(1), 1535750.
˙Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367(6478）.
˙Ministry of Health and Welfare (2024). Administrative Guidelines for Cosmetic Ingredients Derived from Human Cell-Sourced Exosomes.
˙Zhang, Y., et al.(2019).Exosomes: biogenesis, biologic function and clinical potential. Cell Communication and Signaling, 17(1).
˙PIC/S Secretariat (2022). Guide to good manufacturing practice for medicinal products (PE 009-16).