Rutin and quercetagetin enhance the regeneration potential of young and aging bone marrow-derived mesenchymal stem cells in the rat infarcted myocardium.

Myocardial infarction (MI) damages cardiomyocytes permanently and compromises cardiac function. Mesenchymal stem cells (MSCs) with the potential to differentiate into multiple lineages are considered as one of the best options for the treatment of MI. However, aging affects their regeneration capability. With age, reactive oxygen species (ROS) accumulate in cells ultimately causing cell death. To successfully utilize these stem cells in clinic, novel strategies to improve their functional capability should be explored. In this study, we aimed to enhance the cardiac regeneration potential of bone marrow MSCs derived from aging rats by treating them with antioxidants, rutin or quercetagetin in separate in vivo experiments. Oxidative stress was induced by treating MSCs of young and aging rats with different concentrations of H2O2 which resulted in an increase in the ROS level. MSCs were treated with rutin or quercetagetin at varying concentrations and exposed to H2O2. It was observed that both antioxidants significantly (P < 0.001) suppressed H2O2-induced intracellular ROS accumulation in a dose-dependent manner. An optimized concentration of 10 µM rutin or quercetagetin was used for the in vivo experiments. MI models were developed in aging rats by ligation of left anterior descending artery and treated MSCs were transplanted in the MI models. Echocardiography was performed after 2 and 4 weeks of cell transplantation to evaluate the functional status of the infarcted heart and histological analysis was performed after 4 weeks to assess cardiac regeneration. Significant improvement was observed in cardiac parameters including LVEF% (P < 0.001), LVFS% (P < 0.01 and P < 0.001), LVIDd (P < 0.01 and P < 0.001), LVIDs (P < 0.001), LVEDV (P < 0.001) and LVESV (P < 0.001) in the treated young as well as aging MSCs. It is concluded from these findings that rutin and quercetagetin treatment enhance the regeneration efficiency of young and aging MSCs in vivo. These antioxidants can be effectively utilized to improve cellular therapy for myocardial infarction by suppressing ROS production.

Conditioned media trans-differentiate mature fibroblasts into pancreatic beta-like cells.

AIM: The study was carried out to evaluate the role of preconditioning strategies on the trans-differentiation of mature fibroblasts (NIH3T3 cells) into insulin producing ß-cells. METHODS: The NIH3T3 cells were treated with dexamethasone (5µM) and pancreatic extract (0.05 and 0.4mg/mL) separately or in combination. The treated cells were analyzed for the morphological changes, and expression of pancreatic genes and proteins by phase contrast microscopy, RT-PCR and flow cytometry/immunocytochemistry, respectively. RESULTS: Treatment of mature fibroblasts with different combinations of dexamethasone and pancreatic extract in the form of conditioned media resulted in comparable morphological changes and expression of certain pancreatic genes and proteins; however, their expression varied with each treatment. Most prominent effect was observed in case of combined treatment which resulted in significant increase (p<0.001) in gene expression levels of insulin, MafA, and Ngn3. Variable pattern was observed in insulin, MafA, Ngn3 and Sca1 expressions at the protein level. CONCLUSION: It is concluded from this study that preconditioning of NIH3T3 cells with conditioned media containing different combinations of dexamethasone and pancreatic extract can induce trans-differentiation of these cells into pancreatic ß-like cells. The conditioned media however, need to be optimized. The study may offer the possibility of improved regeneration of mature cell type that could serve as a future therapeutic option for diabetes.