Engineered exosome therapeutics for neurodegenerative diseases
Biplob Saikia, Anandh Dhanushkodi
Abstract
An increase in life expectancy comes with a higher risk for age-related neurological and cognitive dysfunctions. Given the psycho-socioeconomic burden due to unhealthy aging in the coming decades, the United Nations has declared 2021–2030 as a decade of healthy aging. In this line, multipotent mesenchymal stromal cell-based therapeutics received special interest from the research community. Based on decades of research on cell therapy, a consensus has emerged that the therapeutic effects of cell therapy are due to the paracrine mechanisms rather than cell replacement. Exosomes, a constituent of the secretome, are nano-sized vesicles that have been a focus of intense research in recent years as a possible therapeutic agent or as a cargo to deliver drugs of interest into the central nervous system to induce neurogenesis, reduce neuroinflammation, confer neuroregeneration/neuroprotection, and improve cognitive and motor functions. In this review, we have discussed the neuroprotective properties of exosomes derived from adult mesenchymal stem cells, with a special focus on the role of exosomal miRNAs. We also reviewed various strategies to improve exosome production and their content for better therapeutic effects. Further, we discussed the utilization of ectomesenchymal stem cells like dental pulp stem cells and their exosomes in treating neurodegenerative diseases. Created with BioRender.com. • MSC-derived exosomes are neuroprotective • Exosomal miRNAs reduce neurodegeneration and neuroinflammation • MSC-Exosome per se can be engineered to cargo biomolecules into CNS • Engineered exosomes can target degenerating tissues or tumor • Ectomesenchymal exosomes may be appropriate to treat neurodegenerative diseases