Theme 4 - Clinical translation: Evaluating clinically-relevant GMP-compatible human cell types in an advanced porcine model of closed chest balloon MI with immunosuppression
Under Theme 4 we will test in an advanced porcine model of MI the three human cell types developed by our scientists including BOECs cells, CD16+CD56- pro-angiogenic monocytes and pericytes. Translation of these cell-based treatments to bed side require the testing of their safety and efficacy in advanced experimental models operated by clinical experts at NHS and GLP standards and highly relevant to human. To be meaningful, these evaluations need to be based on the same quality of in-vivo imaging used in the NHS. In Theme 4 of our Centre, we are using this rigorous preclinical testbed approach taking advantage of the BHF and MRC co-funded Translational Biomedical Research Centre (TBRC) at the University of Bristol.
Theme 3 - Targeting cardiac mesenchyme: Targeting cellular pathways and matrix interactions to drive vascular repair and regeneration
We are using a multidisciplinary approach to identify and characterise the role of mesenchymal cell subpopulations involved in cardiovascular repair, with the ultimate goal of therapeutically targeting and modulating post-myocardial infarction remodelling and repair via cell-based or drug-able approaches.
Theme 2 is developing proangiogenic cellular products starting from human (h) pluripotent stem cells (SC): prevalently embryonic stem cells (ESC), but also induced pluripotent stem cells (iPSC). We develop new RNA biology knowledge and apply it to improve the process of endothelial differentiation of SC. We are also expanding the understanding of extracellular vesicles, especially exosomes, released by SCs and their importance in modulating the paracrine activity of the cells. Exosomes represent a promising option for acellular regenerative medicine.
Vascular endothelial cells play a crucial role in cardiac regeneration, through promoting blood vessel growth and providing morphogenic signals to cardiomyocytes. Both circulating and vessel wall resident endothelial progenitor cells have been implicated in angiogenesis. We are focusing on circulating and resident endothelial pathways to understand the mechanisms driving vascular regeneration.