Extracellular vesicles (EcVs) Therapy
Over 1 billion people worldwide suffer from neurological disorders:
Chronic Neuropathic Pain
Emerging evidence in recent years has shown that the paracrine effects of mesenchymal stem cell (MSCs) are mediated by the secretion of extracellular vesicles (EVs). Exosomes are a subtype of EVs, approximately 30 to 100 nm in diameter, and are released by cells in all living systems. Exosomes are present in body fluids such as blood and cerebrospinal fluid and harbor proteins, lipids, microRNA (miRNA), and RNA. Intercellular communication has been observed in exosomes under various physiological and pathological conditions. MSC exosomes have been studied in various disease models and have shown therapeutic potential in various cancers, strokes, Diabetes, CVD, Autoimmune, Infectious, Parkinson’s disease (PD), Alzheimer disease, MS, and Osteoarthritis (OA),
MESENCHYMAL STEM CELL (MSC)
Identified by Friedensteinin 70’s, expanded by Caplan in 80’s, MSC have been shown to suppress immune responses, enhance neovascularization, and initiate fibroblast and keratinocyte growth.
Key Advantages of Exosomes
Cross the "blood brain barrier".
Can travel via systemic therapy without risk of clumping
Deliver miRNA and mRNA
Not perceived as foreign
Can not transdifferentiate into other cells or into malignant cells
Influence target cells through at least four different mechanisms.
Easy to administer
Easily control dosage
Key Therapeutic Effects of MSC Exosomes
Exosomes The Newest Regenerative Medicine
What are exosomes?
Exosomes are so-called extracellular vesicles, or small bubbles, released from cells, especially from stem cells. They act as shuttles for certain genetic information and proteins to other cells. They allow for cell-to-cell communication, transporting molecules that are important regulators of intracellular information between close and distant cells. They carry information from place to place with different functions and purposes telling cells how and when to react.
How stem cells differ from exosomes?
Exosomes are small signaling proteins that are derived from cells. The ones used in regenerative therapies come directly from stem cells, so even though they are not stem cells, exosomes contain much of the important signaling pathways found in stem cells.
Why exosomes are important?
Exosomes are intelligent tiny “bubbles” filled with precious cargo carefully packaged in lipid spheres. Exosomes travel intact through the bloodstream and easily cross the blood-brain barrier to reach their target organs and tissues. Exosomes help to signal important information to cells that don't communicate well with each other due to a decease process or normal aging.
How do exosomes work?
MSCs were recently renamed “master signaling cells” when it became clear that that injected stem cells themselves did not engraft and grow into new healthy organs and tissues, rather their remarkable benefits came from cell signaling! In other words, MSCs stimulate the recipient’s own cells, including the native or resident stem cells that are found in every organ and tissue of the adult body, to differentiate and proliferate. The cells that do the healing are already there, they just need the proper signals! And it appears that the most effective way for MSCs to deliver their signals is via exosomes.
Exosomes carry genetic information, proteins and messenger RNA. Because of their unique shape and content, they are able to tell cells how and when to react. Exosomes from young stem cells rejuvenate the older cells. They assist in calming an overactive immune system or modulating it to respond in a coordinated and thus more effective fashion.
Exosomes secreted by mesenchymal stem cells (MSCs) contain a diverse array of “signaling molecules” which stimulate growth, healing and tissue, and organ regeneration. Messenger RNA do not multiply themselves but can assist other cells in their proliferation by inserting missing cell information in them.
What are therapeutic uses of exosomes?
Patients with degenerative diseases will benefit the most from exosome therapy. Lyme disease, chronic inflammation, autoimmune disease, and other chronic degenerative diseases are primary candidates for this treatment.
Stem cell-derived exosomes have anti-inflammatory potential. They induce high levels of anti-inflammatory cytokines, and therefore patients with autoimmune, inflammation, and degenerative joint disease may respond to the benefits of exosome therapy. Exosomes may also be beneficial as part of an anti-aging therapy for overall health.
Exosomes and Lyme Disease
Lyme Disease is a very complex disease, caused by the Borrelia burgdorferi bacteria, which compromises the immune system. A combination of factors causes the onset of illness as immune system functions become disrupted leading to diminishing cellular health, immune function, metabolic function and dramatically increasing inflammation.
Many Lyme patients often have dysfunction of the mast cells, increasing their inflammatory response. Inflammation is a central player in most neurodegenerative diseases as well. Incorporating exosomes into a multi modality treatment regimen may help break the inflammatory cycle and provide the body with necessary cellular information to facilitate healing.
Can Patients with Chronic Infections and Autoimmune Diseases Benefit From Exosomes?
One of the key mechanisms controlling the direction of immune responses is a balance between specific immune cells involved in protection vs autoimmune responses, the Th17/Treg ratio. Exosomes from mesenchymal stem cells have shown to normalize the Th17/Treg ratio and bring the deviant immune response back to normal.
Can Exosomes Benefit Neurodegenerative Diseases?
Research has shown that exosomes can penetrate the blood-brain barrier and stimulate neuronal differentiation, neuronal growth, and suppress inflammatory processes within the brain tissue.
What are the benefits of exosome therapy?
The benefits of exosome therapy vary, but most patients report a reduction of the inflammatory symptoms of their chronic disease. This indicates the exosomes are assisting in the repair and regulation process. As time goes on, exosomes will also reprogram the cell function and aid in repair processes. It may take up to four-six months to see the full benefit, but they should last as long as 12 months.
How Are the Exosomes Screened For Safety? Is There Any Risk of Viruses Being Passed on Through Exosomes?
The starting material (mesenchymal stem cells) are GMP laboratory grade, meaning they have been screened for disease, viruses and bacteria.
Is There Any Theoretical Risk of the Body Rejecting Exosomes with Them Being a Foreign Substance?
This is extremely unlikely as there are no immune markers on the surface of the exosomes. They are not cells or tissue. It may be possible to experience die-off reaction after receiving exosomes as these activate the natural killer cells to become T-Regulator cells. For this reason, we always give a small test dose before applying a larger dose.
Human Mesenchymal Stem Cell-Derived Microvesicles Prevent the Rupture of Intracranial Aneurysm in Part by Suppression of Mast Cell Activation via a PGE2-Dependent Mechanism
The Transitioning from Stem Cells to Stem Cell-Derived Exosomes for Treatment of Neurodegenerative Conditions
Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy
Recent Advances of Exosomes in Immune Modulation and Autoimmune Diseases
Extracellular Vesicles: Evolving Contributors in Autoimmunity
A Potent Immunomodulatory Role of Exosomes Derived from Mesenchymal Stromal Cells in Preventing cGVHD
Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis
Exosomes: A Novel Strategy for Treatment and Prevention of Diseases
Emerging Role of Exosomes in the Joint Diseases
Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases
Mesenchymal Stem Cells-Derived Exosomes: A Possible Therapeutic Strategy for Osteoporosis
Mesenchymal Stem Cells-Derived Exosomes are More Immunosuppressive than Microparticles in Inflammatory Arthritis
Macrophage Immunomodulation: The Gatekeeper for Mesenchymal Stem Cell Derived-Exosomes in Pulmonary Arterial Hypertension?
Extracellular Vesicles – the cells’ secret messengers
Introduction to exosomes and other extracellular vesicles – Implications for personalized and precision medicine
Mesenchymal stem cells and exosome therapy
Exosomes and Cardiovascular Function