Investigation of the unique role of non-coding RNAs during endothelial cells differentiation from induced-pluripotent stem cells to treat endothelial cell dysfunction in diabetic complications and coardiovascular disease
Outline, including interdisciplinary dimension
Diabetic vasculopathy and diabetic complications (including cardiovascular disease) are leading causes of mortality and morbidity worldwide. The pathogenic basis for macro and microvascular complications arising from diabetes is complex and multifactorial but a progressive endothelial (EC) dysfunction is critical.
Recently, the ability to derive ECs from induced pluripotent stem (iPS) cells has extended the scientific scope for regenerative medicine. It is now proposed to not only generate rejuvenated and functional cells for cell based therapies but also to be used as powerful models for elucidating the underlying mechanisms towards the development of novel therapies. Interestingly, recent studies have revealed that non-coding RNAs play a big part in epigenetics regulation of gene expression in addition to their roles at the transcriptional and post-transcriptional level and it is speculated that they are attractive candidates for therapeutic targets and biomarkers. We have recently established in CEM novel technologies of iPS cells from human fibroblasts and blood mononuclear cells from healthy volunteers and diabetic patients. The iPS cells have been fully characterised and differentiated towards ECs. RNA –seq analysis has been recently performed in iPS cells during EC differentiation. Interestingly, we have identified a number of novel non-coding RNAs which are shown to have a unique signature in differentiated ECs derived. The proposed study will investigate the role of non-coding RNAs in EC differentiation. This knowledge will provide the tools to generate pure populations of functional ECs to be used as platforms for drug screening, and cell based therapies. The ultimate goal will be to discover novel therapies and identify potential biomarkers of EC dysfunction in diabetic vasculopathy and diabetic complications such as cardiovascular disease.
epigenetics, regenerative medicine, cell therapy, biomaterials