Immunomodulatory oligonucleotide IMT504 improves mesenchymal stem cells proliferation and migration in adult non-obese diabetic mice

GÓMEZ BUSTILLO S; BIANCHI MS; BIANCHI S; LUX-LANTOS VAR; MONTANER AD

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia: SAIC- SAFE ? SAB ? SAP; 2019

Type 1 diabetes (T1D) is a multifactorial autoimmune disease in which insulin-producing pancreatic β cells are destroyed. No effective clinical interventions for T1D are currently available and patients are lifelong treat with insulin. There is a consensus that new innovative approaches are urgently needed to predict, treat, and prevent T1D. Different strategies to modulate immunological response and restore β cell mass have been performed, although limited by the availability of transplants and the need for chronic immunosuppression. IMT504 is the prototype of the PyNTTTTGT family of immunomodulatory oligonucleotides (ODNs) known for their regenerative properties and proven to be effective in lowering glycaemia in non-obese diabetic (NOD) mice. Here, we investigate its action in bone marrow mesenchymal stem cells (BM-MSCs) and splenocytes in NOD/LtJ. BM-MSCs and splenocytes from pre-diabetic and diabetic NOD mice were treated, in vitro, with different doses of IMT504 (0.5, 1.5, 4, 6.5, 10.5, and 20 µg/ml). No differences were observed in splenocytes activation/proliferation at higher doses. Fibroblasts colony forming units (CFU-F) that originate MSCs, viability, and migration assays were assessed. It was determined that 0.5 µg/ml of IMT504 stimulated MSCs (CFU-F (106 seed cells/cm2): IMT504: 85 vs Control: 65 p