Pharmacological preconditioning with phosphodiestrase inhibitor: an answer to stem cell survival against ischemic injury through JAK/STAT signaling

AbstractStem cell transplantation in regenerative medicine has been widely used in various disorders including cardiovascular diseases (CVD) and emerging next-generation therapy. However, transplanted stem cell encountered ischemia/reperfusion (IR) injury which is a major challenge for stem cell survival. During the acute phase after myocardial infarction (MI) cytokine –rich hostile microenvironment, extensive immune cell infiltration and lack of oxygen have been a bottleneck in cell-based therapy. During prolonged ischemia, intracellular pH and ATP level decrease results in anaerobic metabolism and lactate accumulation. Consequentially, ATPase-dependent ion tra nsport becomes dysfunctional, contributing to calcium overload and cell death by apoptosis and necrosis. Although O2 level revitalizes upon reperfusion, a surge in the generation of reactive oxygen species (ROS) occurs with neutrophil infiltration in ischemic tissues further aggravating the injury. Ischemic preconditioning (IPC) of stem cells with a repeated short cycle of IR results in the release of chemical signals such as NO, ROS, and adenosine which triggers a cascade of signaling events that activates protein kinase C (PKC), Src protein tyrosine kinases, and nuclear factor κB (NF-κB) and subsequently increased synthesis of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), Heme oxygenase-1 [HO-1], aldose reductase, Mn superoxide dismutase, and anti-apoptotic genes (Mcl-1, BCl-xL, c-FLIPL, c-FLIPS). Phar...
Source: Heart Failure Reviews - Category: Cardiology Source Type: research