What Are Exosomes?

From Neglected Cellular Waste to a Hot Topic in Biomedical Science!?

Exosomes are small extracellular vesicles (30-150/200 nm in size) secreted by cells. They are formed within the cells and then released into the extracellular environment. These tiny vesicles consist primarily of a lipid bilayer and contain proteins, nucleic acids, lipids, and other bioactive molecules. Initially considered a means for cells to dispose of metabolic waste, exosomes are now widely recognized for their role in intercellular communication. They are the messengers between different cells and tissues, regulating numerous biological processes. Exosomes play key roles in various physiological and pathological processes, including immune responses, cell proliferation, cell development, angiogenesis, anti-aging, and tumor progression. Because different cell types secrete unique exosomes carrying specific biomolecules such as microRNAs and proteins, exosomes have garnered significant interest in biomedical research. Scientists believe exosomes hold potential for disease diagnosis, drug delivery, and therapeutic applications, serving as a window into disease mechanisms.

Exosomes as Bridges for Cellular Communication

Umbilical cord mesenchymal stem cells transfer their active factors to other cells to transmit signals, enhancing communication with neighboring cells or influencing the function of distant target cells. This process offers several advantages, including high safety, low risk of immune rejection, the ability to cross the blood-brain barrier (BBB), anti-inflammatory properties, and anti-aging effects.

Clinical Applications of Exosomes

Exosomes have extensive clinical application potential, primarily in the following three areas:

Value 1

Disease Treatment

Exosome therapy is an innovative biomedical approach that utilizes cell-released microvesicles to treat various diseases. Exosomes contain numerous bioactive molecules, such as proteins, nucleic acids, and lipids, that regulate cell signaling, inhibit inflammation, promote tissue repair, and reduce apoptosis. They have shown potential in treating cancer, cardiovascular diseases, and neurodegenerative disorders.

Value 2

Drug Delivery

Exosomes can serve as drug carriers, encapsulating therapeutic ingredients/components to enhance drug stability and bioavailability. This method shows great promise in treating cancer, neurodegenerative diseases, and inflammatory conditions. Exosomes help deliver drugs precisely to target cells or tissues, reducing toxicity and improving therapeutic efficacy.

Value 3

Disease Diagnosis

Exosomes carry rich biological materials, including proteins, nucleic acids, and lipids. By analyzing their composition, disease markers can be detected, making them useful for early cancer diagnosis, disease monitoring, and prognosis assessment. The molecular profile of exosomes reflects disease progression and provides a basis for evaluating treatment effectiveness.

Advantages of Exosome Therapy

Stem cell-derived exosome therapy is an emerging medical approach with multiple applications and potential benefits for treating degenerative diseases.

Safety
Exosome therapy generally does not trigger immune or rejection responses.
Precision
Exosomes can be engineered to carry specific drugs or molecules for targeted treatment of degenerative diseases.
Broad Applications
Exosomes can be used to treat various degenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), offering vast prospects for medical research.
Tissue Repair
The bioactive molecules in exosomes promote the regeneration and repair of damaged tissues, alleviating symptoms and slowing disease progression.

The table can be scrolled horizontally on mobile devices

  Exosome Therapy Stem Cell Therapy
Biosafety & Compatibility Higher safety and compatibility with minimal immune rejection Potential immune rejection from allogeneic sources
Production Process Exosome sources are single and the production process is quality-controlled Cell sources have individual differences, making quality control more challenging
Storage Stored as a formulation, making preservation easier Requires freezing cells for storage, with relatively complex conditions
Therapeutic Features Anti-inflammatory
Promotes cell proliferation
Tissue repair
Immune modulation
Crosses the blood-brain barrier
Differentiates into various cell types for cell repair and tissue regeneration
Therapeutic Risks It does not replicate in the human body, resulting in a lower risk of carcinogenicity Requires reducing cell proliferation before injection, leading to a relatively higher risk of carcinogenicity

ExoOne's Core Technology and Advantages

ExoOne utilizes umbilical cord mesenchymal stem cells (UCMSCs), which are the youngest and contain abundant regenerative factors

Mesenchymal stem cells (MSCs) can be derived from various sources, including umbilical cord MSCs (UC-MSCs), adipose-derived MSCs (AD-MSCs), and bone marrow MSCs (BM-MSCs). Compared to other stem cell types, umbilical cord MSCs offer advantages such as ease of collection, low immune rejection risk, and abundant cell availability. Studies have shown that exosomes derived from UC-MSCs and BM-MSCs share similarities, but UC-MSCs produce a higher yield of exosomes. UCMSC-derived exosomes (UC-MSC-exosomes) are closely associated with degenerative disease treatment due to their anti-inflammatory and antioxidant properties, which help reduce apoptosis and promote tissue repair. Therefore, UCMSC-derived exosomes are a promising option for treating degenerative diseases.

Exosome Purification Technology

Traditional exosome purification techniques include ultracentrifugation, density gradient centrifugation, polymer precipitation, and immunoprecipitation. While these methods are suitable for small-scale purification, they are time-consuming, yield low purity, and are not industrially valuable. The most commonly used industrial purification methods include size-exclusion chromatography (SEC) and tangential flow filtration (TFF), which enable large-scale preparation, shorter processing time, and improved purity. However, the concentration per unit volume is lower than that of traditional methods.
ExoOne has developed a two-stage tandem purification system, which allows for large-scale production, enhanced purity, and exosome concentrations comparable to traditional methods.

Patents and Technology Transfer

  1. Patent No. M642203: CARE COMPOSITION CONTAINER STRUCTURE CONTAINING EXOSOMES
  2. Patent No. TWI722400B: MESENCHYMAL STEM CELL DERIVED EXOSOMES AND USES THEREOF
  3. Patent No. TWI704923B: FORMULATION COMPRISING EXTRACELLULAR VESICLES, METHOD FOR PRODUCING THE SAME, AND USES THEREOF
  4. Patent No. 1131119000: RADIOLABELED EXOSOME AND METHOD AND KIT FOR PREPARING SAME

Scientific Publications

  1. Lin, T.-Y.; Chang, T.-M.; Huang, H.-C. Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Attenuate Mast Cell Activation. Antioxidants 2022, 11, 2279.)
  2. Lin, T.-Y.; Chang, T.-M.; Tsai, W.-C.; Hsieh, Y.-J.; Wang, L.-T.; Huang, H.-C. Human Umbilical Cord Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Reduce Skin Inflammation In Vitro. Int. J. Mol. Sci. 2023, 24, 17109. https://doi.org/10.3390/ijms242317109
  3. In Vivo SPECT Imaging the Tc-99m Radiolabeled Exosomes from Human Umbilical Cord-derived Mesenchymal Stem Cells in Small Animals. (Under review))