Nicorandil potentiates sodium butyrate induced preconditioning of neurons and enhances their survival upon subsequent treatment with H2O2

Abstract Background Extensive loss of donor neural stem cell (NSCs) due to ischemic stress and low rate of differentiation at the site of cell graft are two of the major issues that hamper optimal outcome in NSCs transplantation studies. Given that histone deacetylases (HDACs) modulate various cellular processes by deacetylating histones and non-histone proteins, we hypothesized that combined treatment with small molecules, sodium butyrate (NaB; a known HDAC inhibitor) and nicorandil, will enhance the rate neuronal differentiation of NSCs besides their preconditioning to resist oxidative stress. Methods NSCs derived from 14-day old Sprague Dawley rat ganglion eminence were characterized for tri-lineage differentiation. Treatment with 1 mM NaB significantly changed their culture characteristics while continuous treatment for 10 days enhanced their neural differentiation. NaB treatment also preconditioned the cells for their resistance to oxidative stress. Results The highest rate of neural differentiation and preconditioning effect was achieved when the NSCs were treated concomitantly with NaB and nicorandil. Cell proliferation assay showed that concomitant treatment with NaB and nicorandil retarded their rate of proliferation. Conclusion These data conclude that preconditioning of NSCs with NaB and nicorandil effectively enhances their differentiation capacity besides preconditioning the cells to support their survival under ischemic conditions

Angiomyogenesis for Myocardial Repair

The conventional therapeutic modalities for myocardial infarction have limited success in preventing the progression of left ventricular remodeling and congestive heart failure. The heart cell therapy and therapeutic angiogenesis are two promising strategies for the treatment of ischemic heart disease. After extensive assessment of safety and effectiveness in vitro and in experimental animal studies, both of these approaches have accomplished the stage of clinical utility, albeit with limited success due to the inherent limitations and problems of each approach. Neomyogenesis without restoration of regional blood flow may be less meaningful. A combined stem-cell and gene-therapy approach of angiomyogenesis is expected to yield better results as compared with either of the approaches as a monotherapy. The combined therapy approach will help to restore the mechanical contractile function of the weakened myocardium and alleviate ischemic condition by restoration of regional blood flow. In providing an overview of both stem cell therapy and gene therapy, this article is an in-depth and critical appreciation of combined cell and gene therapy approach for myocardial repair. Antioxid. Redox Signal. 11, 1929–1944