All cells secrete small membrane-wrapped packages of molecules, known as extracellular vesicles. How the contents and size and patterns of secretion change in response to circumstances remains poorly explored, but it is straightforward enough to harvest these extracellular vesicles from any population of cells grown in culture. It is plausible that near all current applications of stem cell therapy will be replaced by the use of extracellular vesicles derived from stem cells. The incentives point in that direction. Firstly, transplanted stem cells produce benefits via signaling, and most of that signaling is carried in secreted extracellular vesicles. Secondly, logistics of transport, storage, and quality control become easier and less costly when the therapy is harvested vesicles rather than cells.
The authors of today's open access paper make these points along the way to a discussion of the use of extracellular vesicles as a mode of therapy to treat neurodegenerative conditions. The most relevant of the mechanisms reliably affected by delivery of stem cell derived extracellular vesicles is inflammation. Neurodegenerative conditions have a strong inflammatory component, and lasting, unresolved inflammation of brain tissue is clearly associated with dysfunction and cognitive decline. Stem cell therapies and treatment with stem cell derived extracellular vesicles has a robust immunomodulatory effect, reducing chronic inflammation for some months even in people suffering the chronic inflammation of aging.
As the aging population has steadily expanded in recent decades, the incidence of Alzheimer's Disease (AD), Parkinson's Disease (PD), and stroke has continued to rise annually. Stem cells (SCs), a category of undifferentiated cells with the potential for diverse specialization, self-replication, and self-renewal, represent a promising strategy. However, stem cell application encounters significant limitations due to the quality control, immune incompatibility, safety evaluation, ethical considerations and logical considerations, and tumorigenicity.
Extracellular vesicles (EVs) are small bilayer lipid structures discharged by most eukaryotic cells and tissue types. Possessing structures and properties akin to cells, EVs present a distinctive advantage. SC-EVs differ from stem cells in that they neither replicate nor undergo uncontrolled division, which helps avoid issues related to the use of stem cells, such as the risk of tumor formation and the challenges of successful engraftment.
Importantly, SC-EVs possess the ability to cross the blood-brain barrier (BBB) to generate therapeutic impacts within the brain. In addition, SC-EVs enhance the longevity and availability of therapeutic cargo in EV-based nanocarriers compared to EVs derived from other cells, thanks to the immuno-regulating characteristics acquired from the parent cells. It has been also indicated that SC-EVs contribute to favorable outcomes, including extending therapeutic effects, stimulating the immune system, enhancing quality control, and maintaining long-term storage at -80°C. Furthermore, biomedical engineering technology can additionally optimize both the exterior and interior of SC-EVs, enabling them to target particular cells, enhance efficient BBB crossing, and attain specific therapeutic results. Inspiringly, the treatment efficacy of SC-EVs has been extensively explored in diverse neurological disorder models.
In this review, we summarize the methods of obtaining SC-EVs, including the isolation and differentiation of stem cells, and isolation and purification of extracellular vesicles. Then, we review the functions of native SC-EVs, including neuroprotection, angiogenesis, and preservation of BBB integrity, alleviation of neuroinflammation, and other functions. However, there are drawbacks including poor targeting efficiency, inconsistent therapeutic outcomes, and limited output efficiency, which can be solved by precondition, loading drug, and modified surface. Consequently, we summarize the strategies for the engineering of SC-EVs and their applications in AD, PD, and stroke. Ultimately, we outline the challenges linked to these extracellular vesicles in clinical translation and offer potential solutions.
View the full article at FightAging
