Exosomes for treating systemic inflammation

Background

As we age, our cells become damaged, undergo stress, and produce pro-inflammatory cytokines. Increased inflammation combined with a declining immune system contributes to tissue dysfunction and exacerbates the development of age-related diseases. Thus, age-related chronic inflammation, also known as ‘inflammaging’, is a major focus of the aging and longevity field. Typically, anti-inflammatory drugs are prescribed to combat systemic inflammaging, however these drugs can have several side effects. An alternative method to safely reduce inflammaging is greatly needed. Acute, low-grade inflammation is generally beneficial and necessary for proper immune system function and overall health. However, during aging, low-grade inflammation persists into a chronic state for reasons that are not yet known. This age-related chronic inflammation, a.k.a inflammaging, is detrimental to health and contributes to the overall aging process. Methods to safely limit inflammaging without inhibiting all instances of inflammation are currently lacking. We have developed a novel approach to form anti-inflammatory exosomes from mesenchymal stem cells (MSCs), based on the neuropeptide PACAP. Specifically, PACAP-treated MSCs polarized to anti-inflammatory MSCs. Their preliminary data demonstrated three key findings regarding exosomes derived from anti-inflammatory MSCs: - They preserve the anti-inflammatory properties in vivo. - Their delivery can be achieved non-invasively via intranasal administration. - They can alleviate systemic inflammation, increase neurogenesis, and improve cognitive functions In the past few years, interest in the field of exosome research for therapeutic potential has grown tremendously. This is in part due to the fact that exosomes deliver many of the benefits of stem cell therapy, but without most of the major risks. For instance, stem cell transplantation may result in the development of cancer cells. Conversely, exosomes can deliver the same intended cargo as stem cells, but lack the ability to replicate since they are not living organisms. Exosomes are small vesicles that are naturally produced by cells and can be specifically engineered to contain a wide array of nucleic acids, proteins, lipids, carbohydrates, or other types of molecules. Currently, methods and patents already exist to reproducibly obtain exosomes in vitro for therapeutic use in vivo.