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.

Figure 1. Regulated release of therapeutic proteins into the dammaged tissue.

Figure 2. Scheme of the constructs for the regulated therapy of ischaemia with IL-1Ra (IL-1 receptor antagonist, anakinra) and VEGF/PDGF-BB to supress inflammation and promote angiogenesis, respectively.

Ischemic heart disease

Ischemic heart disease is characterized by a reduced blood supply to the heart muscle, usually due to coronary artery disease (atherosclerosis of the coronary arteries). Ischemic heart disease (which includes myocardial infarction, angina pectoris and heart failure when preceded by myocardial infarction) is the leading cause of mortality in most Western countries. Menzin et al. reported a total first-year cost averaged of 32,345 $ and as much as 61% of these costs were due to rehospitalisation (Menzin et al., 2008). Furthermore, survivors of acute myocardial infarction remain at high risk of death in the years after the event (Grothusen et al., 2012).

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