Human iPSC-derived mononuclear phagocytes restore cognition, neural health, and a subpopulation of hippocampal mossy cells in aging mice

ABSTRACT: Young blood or plasma and young bone marrow improves cognitive function in aged animals, though the cell type responsible for these regenerative effects remains unknown. This study evaluated the potential of induced pluripotent stem cell-derived mononuclear phagocytes (iMPs) as a therapeutic for age-associated cognitive and neural decline. Aging mice receiving intravenous delivery of iMPs for 3 weeks showed significant improvements in hippocampusdependent cognitive tasks and neural health markers, including increased levels of the synaptic transporter VGLUT1 and decreases in both astrogliosis and activated microglia. Proteomics on plasma and single nuclei RNA sequencing of the hippocampus identified several key agingspecific pathways. iMP treatment of aging mice was able to reverse the increases in complement and amyloid pathway proteins, restore a lost subpopulation of hippocampal mossycells, and nearly eliminate a population of activated microglia. These findings suggest that iMPs provide a novel individualized therapeutic strategy to target age-related neural decline.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Sarah Parker  

LAB HEAD: Clive Svendsen

PROVIDER: PXD052723 | Pride | 2025-11-10

REPOSITORIES: Pride