Exosomes and Regenerative Medicine
Exosomes play essential roles in intercellular communications.
The exosome was discovered in 1983, when it was found that reticulocytes release 50-nm small vesicles carrying transferrin receptors into the extracellular space. Since then, our understanding of the mechanism and function of the exosome has expanded exponentially that has transformed our perspective of inter-cellular exchanges and the molecular mechanisms that underlie disease progression.
Although the exosome field has rapidly advanced, we still do not fully understand the regulation and function of exosomes in detail and still face many challenges in their clinical application.
Continued discoveries in this field will bring novel insights on intercellular communications involved in various biological functions and disease progression, thus empowering us to effectively tackle accompanying clinical challenges.
A growing body of research has identified a handful of underlying biochemical ‘aging pathways’.
These aging pathways include mitochondrial function, DNA damage, protein synthesis, nutrient sensing, oxidative chemistry and damage, inflammation, senescence and cell processes.
Regenerative medicines can be used to target combinations of the age-related pathways.
Exosomes offer the possibility of treating the underlying causes that make us susceptible to the whole host of illnesses that afflict us with age.
Exosomes, nanoscale packets of biomolecules including proteins and RNA, naturally released by various cells in the body, including stem cells, appear to be a promising regenerative therapy.
The number of extracellular vesicles, or exosomes, that naturally circulate in the human body declines significantly with age. There are also significant differences in the way older individuals’ exosomes are taken up by immune cells, and the immune cells’ subsequent response.
Japanese researchers have begun to elucidate the regenerative properties of circulating exosomes, and an enzyme called eNAMPT that the exosomes carry. This enzyme promotes the production of NAD+, a key component of cellular metabolism previously shown to decline with age, and earmarked as a potentially critical component underpinning age-related disease. In mice and humans alike, levels of eNAMPT in circulating exosomes decline with age.
When the Japanese team dosed aged mice with extra eNAMPT-rich exosomes isolated from young mice, they boosted their health and fitness and extended their lifespan.
This application of exosomes as a health span-extending therapy in humans is an emerging therapy in aging strategies to improve healthspan.
After a heart attack, exosomes can co-ordinate the increased circulation of progenitor cells, which can then increase the level of cardiac repair. Another study published in 2019 showed that myocardial infarction (MI), exosomes secreted by heart muscle stem cells provided cardioprotective effects, activated regenerative signals, and augment cardiac repair.
Exosomes are also seen as useful for treating multiple neurodegenerative diseases due to their anti-inflammatory, neurogenic and neurotrophic effects. In an acute injury, neural stem cell-derived exosomes reduce apoptosis (cell death) and neuroinflammation.
In osteoporosis, exosomes have been shown to promote osteoblast proliferation. In 2019 researchers reported that exosomes could be utilized to treat several skeletal disorders such as osteoporosis and impaired fracture healing.
A NOTE OF CAUTION
There are currently no FDA approved exosome therapeutics and longterm safety is not well proven.
A note from the FDA
“The US Food and Drug Administration (FDA) has authority to regulate regenerative medicine products, including stem cell products and exosome products. There is a lot of misleading information on the internet about these products, including statements about the conditions they can be used to treat. FDA is concerned that many patients seeking cures and remedies may be misled by information about products that are illegally marketed, have not been shown to be safe or effective, and, in some cases, may have significant safety issues that put patients at risk. FDA wants to help consumers be informed about how these products are regulated, and what to look for when considering treatment with one of these products.
Stem cell products are regulated by FDA, and, generally, all stem cell products require FDA approval. Currently, the only stem cell products that are FDA-approved for use in the United States consist of blood-forming stem cells (also known as hematopoietic progenitor cells) that are derived from umbilical cord blood. These products are approved for use in patients with disorders that affect the production of blood (i.e., the “hematopoietic” system) but they are not approved for other uses.
Exosome products are also regulated by FDA. As a general matter, exosome products intended to treat diseases or conditions in humans require FDA approval. There are currently no FDA-approved exosome products.
Anyone considering the use of anything purported to be a regenerative medicine product, including stem cell products, exosome products, or other widely promoted products such as products derived from adipose tissue (this product is also known as stromal vascular fraction), human umbilical cord blood, Wharton’s Jelly, or amniotic fluid should know:
None of these products have been approved for the treatment or prevention of COVID-19, acute respiratory distress syndrome (ARDS), or any other complication related to COVID-19.
None of these products have been approved for the treatment of any orthopedic condition, such as osteoarthritis, tendonitis, disc disease, tennis elbow, back pain, hip pain, knee pain, neck pain, or shoulder pain.
None of these products have been approved to treat any neurological disorder, such as multiple sclerosis, amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease), Alzheimer’s disease, Parkinson’s disease, epilepsy, or stroke.
None of these products have been approved for the treatment of any cardiovascular or pulmonary (lung) diseases, such as heart disease, emphysema, or chronic obstructive pulmonary disease (COPD).
None of these products have been approved to treat autism, macular degeneration, blindness, chronic pain, or fatigue.
FDA has posted information for consumers and patients that discusses the potential risks, and provides advice for people considering the use of these products. Consumers should be cautious of any clinics, including regenerative medicine clinics, or health care providers, including physicians, chiropractors, or nurses, that advertise or offer any of these products. FDA also issued a public safety notification on exosome products on December 6, 2019.”