FOXO3-engineered human mesenchymal stem cells efficiently enhance post-ischemic stroke functional rehabilitation.

Protein Cell

Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

Published: May 2025


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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120242PMC
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FOXO3-engineered human mesenchymal stem cells efficiently enhance post-ischemic stroke functional rehabilitation.

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Forkhead box O3 (FOXO3) has been proposed as a homeostasis regulator, capable of integrating multiple upstream signaling pathways that are sensitive to environmental changes and counteracting their adverse effects due to external changes, such as oxidative stress, metabolic stress and growth factor deprivation. FOXO3 polymorphisms are associated with extreme human longevity. Intriguingly, longevity-associated single nucleotide polymorphisms (SNPs) in human correlate with lower-than-average morbidity from cardiovascular diseases in long-lived people.

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FOXO3 is an evolutionarily conserved transcription factor that has been linked to longevity. Here we wanted to find out whether human vascular cells could be functionally enhanced by engineering them to express an activated form of FOXO3. This was accomplished via genome editing at two nucleotides in human embryonic stem cells, followed by differentiation into a range of vascular cell types.

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