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Optimising cardiac stem cell therapy by finding the best conditions for the cells in the lab and in the heart

Carr group research
Stem cell-derived cardiomyocytes grown as engineered heart tissue (left); stained to shown contractile proteins (centre); and electron microscopy showing stem cell-derived cardiomyocytes grown in a porous collage scaffold (right).

We are studying cardiac progenitor cells for use in therapy and for disease modelling. We have shown that cardiac progenitor cells, isolated and expanded from biopsy samples of the heart, and induced pluripotent cells, differentiated towards a cardiac phenotype, significantly improved function of the heart after myocardial infarction. However, with both cell types, the cell retention is low and the improvement in function is not large. To improve the efficacy of the cell therapy, we are investigating tissue engineering strategies to deliver cells as a bandage across the infarct scar, and whether addition of hypoxic microRNAs to the cells can increase cell survival after administration to the heart

We are measuring changes in cell metabolism as the cells differentiate into cardiomyocytes. By characterising the metabolism of human induced pluripotent cells that have been differentiated into beating cardiomyocytes, we can explore the use of these cells to detect metabolic side-effects of potential drug compounds or to explore the effect of cellular defects on cardiac metabolism. When the cells are grown as a monolayer, they retain a very immature metabolic profile, so we are growing them as 'Engineered Heart Tissue', where the cells are held in a gel between two flexible posts, so that they have to work to contract. In addition, we change the culture medium to provide a combination of nutrients more representative of that which the cells experience in the heart. We have shown that this induces a metabolic profile more like that of an adult human heart cell and are now going on to explore different disease models in this system.

 

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