Exosome therapy is an up and coming new medicinal technology that leverages the powerful mechanisms of exosomes. Exosomes are naturally derived vesicles that contain molecular components that exert potent biological effects throughout the body. Science has recently evaluated how engineering these exosomes could help treat certain diseases. For example, research is currently underway characterizing the role of exosome therapy in conditions related to autoimmunity, anti-aging, neurodegeneration, and healing.
Though results seem promising, there is still much research to be done to adequately assess the benefit risk profile of exosome therapy, as no exosome therapy is currently FDA approved it is starting to be used in a research capacity. This article will discuss the science of exosomes and how medicine may be able to use exosomes to treat disease.
Exosomes contain several types of molecules within a lipid membrane. These molecules can include proteins, nucleic acids, and metabolites. Various cells release exosomes, which then relay messages via fusion with membranes, surface receptors, and more.
In conjunction with its components, exosomes function as messengers within the body, communicating regarding numerous biological processes. Exosome messaging can signal either the promotion or inhibition of disease, explaining its potential in cardiovascular disease, cancer, immune response, the central nervous system (CNS), and pregnancy. Likewise, exosomes may be possible biomarkers for certain conditions like cancer and Alzheimer’s.
Recent scientific advances leverage exosomes to deliver certain substances and pharmacologic agents throughout the body. If successful, exosomes would represent a new treatment technology that can induce therapeutic effects (1,2).
Scientists have begun leveraging the potent biological activity of exosomes to provide treatment for a variety of conditions. Exosome therapy represents a new form of regenerative medicine, as it assists the body in healing itself with the help of some careful engineering.
In exosome therapy, exosomes are taken from human cells, sterilized, and then altered to include certain proteins, lipids, messengers, and/or genetic material aimed at healing a specific condition. A professional then administers the exosome therapy via an injection or the intravenous (IV) route.
Exosome therapy can target a wide array of conditions. In particular, the medical field has leveraged exosomes for conditions involving the joints, inflammation, pain, cognition, and immunity.
As previously mentioned, exosomes represent a potential regenerative technology. This is because exosomes play a role in organ development, and they also contribute to regeneration after disease or injury. Certain substances that promote healing can be packed into exosomes so that they can be delivered to your cells and tissues to promote tendon, skeletal muscle, and peripheral nerve healing. However, these studies only demonstrate efficacy in preclinical models, although clinical trials evaluating exosome therapy in tendon, nerve, and tissue repair are underway (4).
Aging, though a natural part of life, can be particularly troubling for some people, specifically with regards to the cosmetic implications of getting older. With increased age, you may notice skin wrinkling, sagging, and discoloration. These are the result of senescence of the skins cells, meaning skin cells do not grow and divide as much as they used to.
Exosomes provide a potential therapy for those looking to improve the appearance of their skin. In the lab, exosomes have demonstrated effects in preventing skin cell senescence. Additionally, they may increase collagen production and decrease reactive oxygen species (ROS), which are harmful to your body and skin (5).
Recent research shows that exosomes play a role in the pathogenesis of AIDs, suggesting exosomes’ potential role in controlling immune responses. This makes sense, because exosomes contain molecules like receptors and ligands that are important to mounting an immune response. Additionally, they can also contain genetic material that can either activate or suppress the immune system. Thus, there are two ways in which exosomes affect immunity: via direct interactions with target cells and via miRNA (6). Research suggests that several autoimmune conditions may benefit from exosome-mediate therapy. These conditions include rheumatoid arthritis (RA), systemic sclerosis, systemic lupus erythematosus (SLE), ulcerative colitis, autoimmune thyroiditis (AITD), hemolytic anemia, and more (7).
In the context of neurodegenerative diseases, exosomes may help promote or prevent accumulation of misfolded proteins in the brain, which are harmful. They may also help get rid of misfolded proteins. Other studies have observed the presence of certain proteins of interest in cognitive conditions in exosomes. For example, research demonstrates the presence of Tau and B-amyloid, proteins important to Alzheimer’s disease, and a-synuclein, a protein important in Parkinson’s disease, in exosomes (2).
Several studies have evaluated how exosomes may benefit neurodegenerative diseases. For example, one study put catalase into exosomes. The exosomes delivered these antioxidant substances to neuronal cells in the brains of mice (1).
Risks and Side Effects of Exosome Therapy
Overview of potential risks
The Food and Drug Administration (FDA) strictly regulates exosome products. While exosome therapy shows much promise, the FDA has not currently approved any exosome products for any indications. Thus, the risk-benefit profile of these therapies has not been adequately assessed by experts in the field. Because the safety profile is not fully characterized, there are both known and unknown risks associated with exosome therapy.
In terms of arising safety concerns, the FDA issued a public safety notification in 2019 with regards to exosome products. Patients in Nebraska treated with unapproved exosome products reported several adverse events. One such adverse event included bacterial infections (8,9).
In addition to the potential risks and side effects of exosome therapy, there are also several challenges to their development. One of these issues relates to production. Developing and manufacturing exosomes is time and resource-intensive, as the process involves extraction and sterilization. Additionally, not all exosomes are created equally. The quality, safety, and effectiveness of an exosome is dependent on the source of the exosome, including the cell type and culture conditions. Finally, though some initial research exists on exosome therapy, large clinical trials in humans are lacking compared to other types of treatment. However, it is still a relatively new technology, and presently 100 clinical trials involving exosomes have been initiated (1).
Scientists have identified around 10,000 proteins, 3,000 miRNAs, 1,000 lipids, and 3,000 mRNAs within exosomes. With the diverse biological components present in exosomes, the possibilities in exosome therapy seem to be infinite.
As aforementioned, scientists may be able to leverage exosomes to deliver certain molecules and pharmacological agents into the body via a unique mechanism. Researchers have isolated exosomes from mesenchymal stem cells (MSCs), which offer regenerative potential (10).
Exosomes could be a key contributor to both diagnosis and treatment in the clinical setting. The benefits of exosomes as a potential treatment modality include their small size, low immunogenicity, and their ability to penetrate certain barriers throughout the body. However, the use of exosomes may be limited for other reasons, including their rapid clearance from the body and non-specific targeting.
Exosomes have potential to house and deliver small molecules, proteins, and genetic material. In terms of small molecules, research has demonstrated exosome’s ability to deliver doxorubicin or paclitaxel, two important medications in cancer treatment. Studies demonstrate exosomes may be more effective in targeting cancer cells and may increase drug delivery. With regards to proteins, exosomes may be able to deliver protein-based substances such as enzymes and antigens.
Exosomes may also have a place in gene therapy because of their ability to protect nucleic acids like siRNA and mRNA. One study, for example, demonstrated the ability of a miRNA-containing exosome to prevent cancer cell growth and spread (1).
Several pharmaceutical and biotechnology companies are engaged in exosomal research with the intent to eventually achieve FDA approval and market these therapies. For example, Kimera Labs is analyzing exosome therapy in the context of tissue healing and scarring. Evox Therapeutics is studying exosomes for certain rare metabolic and lysosomal storage conditions (10).
To wrap up, remember these key points regarding exosomes and exosome therapy:
The future of exosome therapy is bright, with over 100 clinical trials underway evaluating their use cases in an array of disease states. Exosome therapy offers a potential treatment solution for many, however, future research is needed to fully understand their benefits and risks.