A major trend in the world of stem cell therapies is the replacement of stem cell transplantation with the use of extracellular vesicles derived from those stem cells. Extracellular vesicles are much more easily managed as a basis for therapy, they are more easily stored and transported, and their production can be more centralized. Since stem cell therapies produce their benefits largely via the signals generated by the transplanted cells in the short period before they die, the use of stem cell derived extracellar vesicles appears a good substitute. The availability of extracellular vesicle therapies is spreading in the medical tourism community, where good data on outcomes is very hard to come by, and the more mainstream medical development community has started towards clinical trials and robust manufacturing approaches. One should probably expect to see a rerun of the trajectory of stem cell transplants over the past twenty years, slowly moving from initially widespread use in clinics in less regulated regions of the world to more codified and narrower uses within the heavily regulated clinical systems of Europe and the US.
Neuroaging is a complex biological process in which the brain undergoes progressive functional decline marked by synaptic loss, neuroinflammation, and cognitive decline. At the molecular and cellular level, aging is driven by multiple interconnected hallmarks, including genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Among these, cellular senescence, a state of irreversible cell cycle arrest, has emerged as a critical contributor to brain aging. Senescent cells accumulate with age, driven by the p53-p21 and p16-pRb pathways, and secrete pro-inflammatory factors via senescence-associated secretory phenotype (SASP), thereby exacerbating neurodegeneration, vascular dysfunction, and cognitive decline.
Extracellular vesicles (EVs) are natural nanocarriers of proteins, lipids, and nucleic acids, and have emerged as key mediators of intercellular communication and therapeutics for aging and age-related conditions. EVs derived from various cell types, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs), can modulate senescence-related pathways, reduce inflammation, and promote tissue repair. Preclinical studies demonstrate that stem-cell-derived EVs can improve cognitive performance, enhance neurogenesis, reduce senescence phenotype, improve neuronal survival through neuroprotective miRNAs (miR-181a-2-3p), suppress neuroinflammation via inhibition of NLRP3 inflammasome, and support synaptic plasticity. Stem cell EVs possess natural biocompatibility, the ability to cross the blood-brain barrier (BBB), and targeted delivery mechanisms, making them promising candidates for anti-aging interventions.
Link: https://doi.org/10.20517/evcna.2025.65
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