Co-culture of gene transferred endothelial cells with arterial cells could prevent restenosis

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Researchers at the Perelman School of Medicine in Philadelphia have trialed a co-culture cell therapy for restenosis. The novel method utlisied magnetically facilitated gene transfer to heighten the therapeutic effects of endothelial cells (EC) in the protective endothelial layer.

Susceptibility to restenosis, along with thrombosis and neoatherosclerosis, are effects of the incomplete or slow regrowth of the endothelial layer following an angioplasty to treat atherosclerotic obstruction. Recovering the endothelium rapidly post – treatment is therefore a desirable to maximize the efficacy of the initial interventions and to prevent the occurrence of secondary conditions. Thus restoring or enhancing the functionality of EC in angioplasty patients was the target of the work done by the team at Perelman.

An increase in EC-associated nitric oxide (NO) synthesis has been associated with an increase in paracrine activity and restoring the function of EC. In the study, Bovine aortic EC were magnetically transduced with NO synthase (NOS) adenovirus (Ad), which was formulated in zinc oleate-based magnetic nanoparticles (MNP[iNOSAd]). The effect of these gene transferred cells when co-cultured with arterial smooth muscle cells (A10 cell line) was studied. The A10 cell line was one that exhibited the defining characteristics of neointimal cells; these proliferate following damage to the arterial wall and cause the lining of the artery to thicken – resulting in restenosis. The study found that the gene transferred EC exhibited pronounced antiproliferative activity toward co-cultured A10 cells. One of the routes for this was the attenuation of the stimulatory effect of a potent mitogen, platelet-derived growth factor (PDGF-BB).

The team responsible for the work, which is published in Drug delivery and translational research, concluded: ‘these results show feasibility of applying magnetically facilitated gene transfer to potentiate therapeutically relevant effects of EC for targeted cell therapy of restenosis. The direct contact co-culture methodology provides a sensitive and reliable tool with potential utility for a variety of biomedical applications.’

Source: Optimizing endothelial cell functionalization for cell therapy of vascular proliferative disease using a direct contact co-culture system. Batting M R et al., Drug delivery and translational research, July 2017. DOI