In Vivo Molecular Imaging Of Rosuvastatin On Adipose-derived Mesenchymal Stem Cells' Survival And Mechanisms In Post-Infarcted Mice Hearts

BackgroundRecently, due to their abundant source and proved pluripotency, adipose-derived stromal/stem cells (AD-MSCs) have been extensively studied for their therapeutic potential for myocardial infarction (MI). However, the harsh environment in the cardiac tissue after MI, which was characterized by local inflammation and ischemia, induced substantial loss of transplanted AD-MSCs. HMG-CoA reductase inhibitors have been shown to suppress inflammation and promote survival of stem cells, so we postulate that the combination of AD-MSCs transplantation and Rosuvastatin administration may result in a synergistic effect on myocardial repair and functional improvement.Methods and resultsAdipose tissue derived mesenchymal stem cells (AD-MSCs) which stablely expressed firefly luciferase (Fluc) were isolated from ?-actin-luc transgenic mice and characterized by flowcytometry and bioluminescence imaging (BLI). AD-MSCs were positive for the CD44 and CD90 by flowcytomytry . The Firefy luciferase expression was well corelatted with cell numbers which was proved by both BLI and luciferase assay. Myocardial infarction was created in inbred mice by coronary ligation,AD-MSCs were transplanted into the hearts of MI mice with or without Rosuvastatin pretreatment. Transplanted AD-MSCs were tracked by longitudinal bioluminescence imaging. Four and six weeks after transplantation, cardiac function and structure were evaluated by serial echocardiography. Rosuvastatin and AD-MSCs treated mice consistently exhibited better cardiac function than control mice evaluated by small animal echocardiography. AD-MSCs were subjected to (1) normal control ; (2) Hypoxia 6hrs+ Reoxygen 42hrs (H/R) (3) H/R+Rosuvastatin (10^-8,10^-7,10^-6mol/L respectively). Cell survival and proliferation were assessed by BLI and MTT assays.The protein expressions of Akt, Akt, Erk and pErk were analyzed by Western blot assay. Administration of Rosuvastatin increased proliferation of AD-MSCs under hypoxia compared with control groups. (P<0.05). Western blot assay revealed that the levels of phosphorylated Akt and phosphorylated Erk were higher in Rosuvastatin group than that in H/R group.ConclusionNoninvasive imaging could be a valuable tool for monitoring stem cell treatment. Rosuvastatin treatment may protect the myocardium undergoing acute infarction by creating a better environment for the survival of implanted AD-MSCs. Rosuvastatin promoted the proliferation of AD-MSCs after H/R injury by AKT and ERK.