Priming mesenchymal stem cells with uric acid enhances neuroprotective properties in parkinsonian models

Abstract

Mesenchymal stem cells (MSCs) are a potential source of cell-based disease-modifying therapy in Parkinsonian disorders. A promising approach to develop in vitro culture methods that mimic natural MSC niche is cell priming. Uric acid (UA), a powerful antioxidant, scavenges reactive oxygen species, which has a vital role in maintaining self-renewal and differentiation potential of MSCs. Here, we demonstrated that UA treatment in naïve MSCs stimulated glycolysis and upregulated transcriptional factors responsible for regulation of stemness, leading to increase in the expression levels of osteogenesis-, adipogenesis-, and chondrogenesis-related genes. UA-primed MSCs had more enhanced neuroprotective properties in cellular and parkinsonian animal models compared to naïve MSCs by inhibiting apoptotic signaling pathways. Additionally, expression of miR-137 and miR-145 was decreased in UA-treated MSCs. Our data demonstrated that priming MSCs with UA augment neuroprotective properties through enhanced self-renewal and differentiation potential, suggesting a practical strategy for improving the application of MSCs in parkinsonian disorders.