Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation

摘要: Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response alloantigens. However, relatively little has been reported regarding potential of abilityof these synergize. Thus, in present study, we aimed investigate OX40-Ig fusion protein (OX40Ig) expression ADSCs validate their more potent immunosuppressive activity preventing renal allograft rejection. For this purpose, from Lewis rats were transfected with recombinant plasmid, pcDNA3.1(-)OX40Ig, by nucleofection. The transduced plasmid (termed ADSCsOX40Ig) or untransduced ADSCsnative) added allostimulated mixed lymphocyte reaction (MLR) vitro. In vivo, ADSCsOX40Ig, ADSCsnative, PBS administered an allogeneic transplantation model, therapeutic effects, as well underlying mechanisms examined. results revealed both ADSCsnative ADSCsOX40Ig significantly suppressed T proliferation increased percentage CD4+CD25+ regulatory cells MLR assays, being effective. Furthermore, our vivo experiments compared group, administration autologous markedly prolonged mean survival time grafts, reduced rejection, downregulated mRNA intragraft interferon-γ (IFN-γ) , upregulated interleukin (IL)‑10, transforming growth factor-β (TGF-β) forkhead box 3 (Foxp3). findings study indicate use is a promising strategy for This provides synergistic benefits ADSC modulation OX40-OX40L pathway blockade, may therefore clinical transplantation.