Intranasally delivered mesenchymal stromal cells decrease glial inflammation early in prion disease

• DOI: 10.3389/fnins.2023.1158408
• Publication Date: 2023-05-12T05:39:50Z
• Authors: Arielle J. D. Hay; Amanda S. Latham; Genova Mumford; Amelia D. Hines; Sydney Risen; Elizabeth Gordon; Connor Siebenaler; Vincenzo S. Gilberto; Mark D. Zabel; Julie A. Moreno
• Keywords: Astrogliosis

Mesenchymal stromal cells (MSCs) are an intriguing avenue for the treatment of neurological disorders due to their ability migrate sites neuroinflammation and respond paracrine signaling in those by secreting cytokines, growth factors, other neuromodulators. We potentiated this stimulating MSCs with inflammatory molecules, improving migratory secretory properties. investigated use intranasally delivered adipose-derived (AdMSCs) combating prion disease a mouse model. Prion is rare, lethal neurodegenerative that results from misfolding aggregation protein. Early signs include neuroinflammation, activation microglia, development reactive astrocytes. Later stages vacuoles, neuronal loss, abundant aggregated prions, astrogliosis. demonstrate AdMSCs upregulate anti-inflammatory genes factors when stimulated tumor necrosis factor alpha (TNFα) or prion-infected brain homogenates. TNFα performed biweekly intranasal deliveries on mice had been intracranially inoculated mouse-adapted prions. At early disease, animals treated showed decreased vacuolization throughout brain. Expression associated Nuclear Factor-kappa B (NF-κB) Nod-Like Receptor family pyrin domain containing 3 (NLRP3) inflammasome were hippocampus. AdMSC promoted quiescent state hippocampal microglia inducing changes both number morphology. Animals received decrease overall astrocyte number, morphological indicative homeostatic Although did not prolong survival rescue neurons, it demonstrates benefits combatting