Investigating the role of the histone deacetylases-inhibitor suberanilohydroxamic acid in the differentiation of stem cells into insulin secreting cells

Introduction: The United Arab Emirates has the second incidence of diabetes in the world. The current diabetes management plans are associated with many complications and do not provide a cure. Stem cells offer hope for permanent alleviation of this health problem through the possible differentiation into insulin-secreting cells. The current methods for the differentiation do not produce homogeneous beta-cell populations. Histone deacetylation is an epigenetic silencing mechanism that can render many genes irresponsive to the induction protocols. This study aimed at investigating the effect of the histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) on the production of functional beta cells, based on a mesenchymal stem cells model. Methods: MG63 cells were treated for three consecutive days with SAHA, followed by a three-steps of beta cells differentiation protocol, with media-contained retinoic acid, epidermal growth factor, nicotinamide and exendin-4 at different stages. Then, glucose-stimulated insulin secretion was conducted to assess the functional state of the differentiated cells. Results: Pretreating the cells with SAHA enhanced the insulin production and secretion in comparison to the control (PBS) and the vehicle dimethyl sulfoxide, as shown by the immunofluorescence detection of insulin and the transcription factor “PDX1”, as well as an increase in insulin secretion in the media. Gene expression analysis showed that SAHA pretreated cells had more induction of the studied markers when challenged with high glucose level. Conclusion: Such findings indicate a novel approach to enhance the ability of stem cells to differentiate into insulin-producing cells with potential therapeutic implications

Two faces of the coin: Minireview for dissecting the role of reactive oxygen species in stem cell potency and lineage commitment

Reactive oxygen species (ROS) are produced as by-products of several intracellular metabolic pathways and are reduced to more stable molecules by several protective pathways. The presence of high levels of ROS can be associated with disturbance of cell function and could lead to apoptosis. The presence of ROS within the physiological range has many effects on several signalling pathways. In stem cells, this role can range between keeping the potency of the naive stem cells to differentiation towards a certain lineage. In addition, the level of certain ROS would change according to the differentiation stage. For example, the presence of ROS can be associated with increasing the proliferation of mesenchymal stem cells, decreasing the potency of embryonic stem cells and adding to the genomic stability of induced pluripotent stem cells. ROS can enhance the differentiation of stem cells into cardiomyocytes, adipocytes, endothelial cells, keratinocytes and neurons. In the meantime, ROS inhibits osteogenesis and enhances the differentiation of cartilage to the hypertrophic stage, which is associated with chondrocyte death. Thus, ROS may form a link between naïve stem cells in the body and the environment. In addition, monitoring of ROS levels in vitro may help in tissue regeneration studies. Keywords: Stem cells, Reactive oxygen species, Differentiation, Osteogenesis, Potenc