Definition and Overview
Exosomes are nano-sized (30-150 nm) extracellular vesicles (EV) that originate from intracellular multivesicular bodies (MVBs) and are released outside the cell when fused with the cell membrane. It is secreted by all cells and functions as an important means of intercellular signaling, including proteins, miRNAs, mRNA, DNA, and lipids.
Exosome therapy is a method of inducing tissue regeneration, anti-inflammatory, and neuroprotective effects by administering exosomes for therapeutic purposes into the body. After research showed that much of the therapeutic effect of stem cells is mediated through exosomes secreted rather than the cells themselves, exosomes are attracting attention as a 'cell-free therapy' that uses exosomes without cell transplantation.
Composition and biological properties of exosomes
Exosomes are vesicles surrounded by a phospholipid bilayer membrane, and their interior contains hundreds to thousands of proteins (surface markers such as CD63, CD81, and CD9), nucleic acids (miRNA, mRNA, ncRNA), and lipids.
The ability to cross the blood-brain barrier (BBB) is an important property of exosomes. Exosomes can be delivered across the BBB to the central nervous system through their small size and special surface molecules, showing potential for treating brain diseases that are difficult to access with existing drugs.
Exosomes show low immunogenicity, resulting in low immune response even during allogenic administration. This increases treatment accessibility by eliminating the need for autologous cell collection.
Mesenchymal stem cell-derived exosome (MSC-exosome)
Exosomes secreted by mesenchymal stem cells (MSCs) are the most studied therapeutic exosomes. MSC-exosomes exhibit anti-inflammatory, immunomodulatory, neurotrophic, and angiogenic effects similar to those of parental cells (MSCs).
In a myocardial protection study, MSC-exosomes significantly reduced myocardial ischemia-reperfusion injury, showing a similar effect to direct MSC transplantation.
In a stroke model, intravenous administration of MSC-exosomes resulted in recovery of neurological function, angiogenesis, and increased neuroplasticity. This effect is related to the mechanism by which miRNAs, such as miR-133b in exosomes, regulate the expression of nerve growth-related genes.
Nervous system applied research
A phase 1 clinical study of MSC-exosomes in post-stroke rehabilitation is ongoing. Preclinical research data is also accumulating in traumatic brain injury (TBI), spinal cord injury, ALS, and Parkinson's disease. The possibility of promoting recovery through delivery of neurotrophic factors in peripheral nerve damage and autonomic nerve dysfunction is also being studied. The possibility of special exosomes (derived from IFNγ-stimulated dendritic cells) to induce myelin regeneration in multiple sclerosis has been reported.
Manufacturing and standardization challenges
The key tasks for clinical translation of exosome therapy are standardized manufacturing and quality control. The characteristics vary depending on the exosome isolation method (ultracentrifugation, size exclusion chromatography, precipitation reagent), and the source of the manufactured cells, culture conditions, and storage method affect efficacy. The Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines have been proposed to standardize studies.
Comparison: Exosomes vs Stem Cell Therapy
The advantages of exosome therapy include a low risk of pulmonary embolism, immune rejection, and tumor formation due to cell transplantation, ease of cryopreservation and long-term storage, the ability to cross the blood-brain barrier, and the possibility of developing a standardized formulation. Disadvantages include lack of manufacturing standardization, mass production costs, and lack of clinical evidence.