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Ischaemic heart disease

We designed a device for the therapy of myocardial ischaemia, composed of microencapsulated mammalian cells that include a genetic bistable toggle switch with a positive feedback loop, where in one state the cells produce anakinra as the anti-inflammatory effector and in the second state they produce a stoichiometric amount of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor B (PDGF-BB) to promote angiogenesis in the damaged tissue.

A pharmacokinetic model demonstrated that implantation of the device into the injured heart tissue results in a high level of anakinra concentration within the affected tissue, while the systemic level of anakinra is very low, preventing systemic immunosupression.

We demonstrated that the production level of anakinra by engineered cells is sufficient for the therapeutic implementation of microencapsulated cells for this indication.


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