The Analyze Blog

Inducing Angiogenesis in Chronic Vascular Occlusion

By AnalyzeDirect Staff, last updated March 17, 2016

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Gene and Cell TherapyGene therapy and cell therapy belong to a novel therapeutic branch of modern medicine, the goals of which are repairing the direct cause of genetic diseases in the DNA and restoring damaged tissues or organs, respectively. In chronic vascular occlusion, stem cell therapy can be used to help regenerate myocardial tissues and return the contractile function of the heart by re-establishing the microenvironment existed prior to the myocardial infarction.

Although accumulating data supports the efficacy of intramyocardial cell- and gene-based therapy, their use in the managment of cardiovascular diseases remains extremely challenging and several obstacles need to be addressed. For instance, some of the limitations consist of filling the lack of sufficient site specific targeting, assuring cell retention, and fighting dissipation and dispersion of gene or cell product within the wider vascular system.

In order to achieve therapeutic delivery at a safe local dose and enhance site specific angiogenesis – the physiological process through which new blood vessels form from pre-existing ones – researchers at University College Cork in Ireland have developed a new percutaneous vascular access technology in a model of chronic myocardial ischemia.

They synergized cell and gene therapy benefits and designed a way to deliver autologous smooth muscle cells, engineered with an angiogenic gene, to a site of chronic vascular occlusion. These cells were selected as a conduit for VEGF delivery and expression, a signaling protein that stimulates growth of blood vessels. VEGF’s normal function is to create new blood vessels during embryonic development in the womb, but also after injury in order to bypass blocked vessels.

The study was performed in a porcine model with chronic total occlusions, a heart disorder characterized by the presence of heavy plaque burden within the artery, resulting in complete occlusion of the vessel. The investigators were able to prove retention of the cell mass, which was confirmed using green fluorescent protein tracking. Above all, their results showed that their cell/gene delivery system improved cardiac function by increasing the formation of endothelial cell colonies.

Three dimensional images of coronary arteries were displayed using Analyze software and micro-CT and CT contrast image analysis revealed that VEGF delivery enhanced microvessel spatial density and regional cardiac function, respectively.

This technology has the scope to offer patients who are not candidates for a coronary artery bypass grafting (because of the poor condition of distal blood vessels), an alternative revascularization strategy and a comparable treatment.

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