1857-P: Modified Mesenchymal Stromal Cells: A Novel and Safe Therapy for Treating Nonalcoholic Fatty Liver Disease (NAFLD) in Obesity and Diabetes

Background: Mesenchymal stromal cells (MSCs) can home-in to inflamed fat depots to deliver antioxidants locally and help reduce oxidative stress, inflammation and improve NAFLD in high-fat diet (HFD) induced obese (DIO) diabetic mice. Methods: Antioxidants Sod2 (mitochondrial), Catalase (cytosolic) or Null (control) genes were upregulated individually, or in combination in adipose-derived MSCs. Modified MSCs were examined in-vitro in presence of adipogenic media to mimic DIO milieu. Next, modified MSCs were delivered intraperitoneally (IP) in mice that received 45% or 60% HFD for 8 to16 weeks. Results: In-vitro, we noted reduced MSC lipid droplets with SOD2, Catalase and combination compared to Null. Inflammatory marker IL6 mRNA, was down-regulated in SOD2, Cat and combination MSCs vs. Null-MSCs. In-vivo, n=4, Glucose tolerance test (GTT) improved with SOD2 MSC delivery in (p=0.07) at week-4. Plasma inflammatory marker TNFa, was reduced in both SOD2 and Catalase MSC groups (p