Mesenchymal cell-derived extracellular vesicles ameliorate age-related deficits in working memory and in vivo MRI measures of white matter structure and function in rhesus monkeys
Recommended Citation
Mackie EC, Cheng CH, Alibrio MN, Rutledge C, Xin H, Chopp M, McCann RP, Rosene DL, Yang Q, Zeldich E, Medalla M, Koo BB, and Moore TL. Mesenchymal cell-derived extracellular vesicles ameliorate age-related deficits in working memory and in vivo MRI measures of white matter structure and function in rhesus monkeys. Geroscience 2025.
Document Type
Article
Publication Date
12-2-2025
Publication Title
Geroscience
Keywords
Cognition; Diffusion MRI; Mesenchymal stromal cell-derived extracellular vesicles; Normal aging; Resting-state functional MRI; Rhesus monkey
Abstract
Aging humans and non-human primates both exhibit a similar pattern of cognitive decline beginning in middle age that is characterized by progressive impairments in rule learning, executive function, and working and recognition memory-functions often associated with dysfunction of prefrontal and medial temporal lobe regions. The heterogeneity and inter-subject variability in aging and age-related cognitive impairments present challenges for developing effective therapeutics and can be attributed to differing degrees of cortical white matter (WM) damage and alterations to local and long-range prefrontal and temporal networks. A promising therapeutic that has been shown to be efficacious in mitigating WM damage and improving cognitive function in rodent models is mesenchymal cell-derived extracellular vesicles (MSC-EVs). In the present study, late middle-aged rhesus monkeys were systemically administered monkey-derived MSC-EVs every 2 weeks for 18 months. We demonstrate that MSC-EV treatment improves spatial working memory and decreases the frequency of perseverative responses with largely no effects on recognition memory. These cognitive improvements were associated with increases in MRI diffusion measures of WM structural integrity over time as well as preservation of inter-network functional connectivity as measured by resting-state functional MRI. These findings suggest that MSC-EV treatment can slow or reverse age-related cognitive decline while strengthening WM integrity and improving functional connectivity in late middle-aged rhesus monkeys.
PubMed ID
41329450
ePublication
ePub ahead of print
