Question: 

During vascular diseases such as atherosclerosis endothelial cell (EC) damage occurs resulting in the loss of endothelium-dependent vasorelaxation and providing sites for thrombosis.

Methodology: 

In order to restore endothelial function we have developed a method to transduce ECs with lentiviral vectors (LVs) that allow for the expression of functional genes in situ. To achieve an efficient transduction LVs were complexed with magnetic nanoparticles (MNPs). In addition, a special magnetic device was designed to obtain a radially symmetric magnetic field with a high gradient at the vascular wall.

Result: 

As a proof of concept we show that complexes of MNPs and LVs carrying an eGFP expression cassette can be trapped in a radially symmetric manner in an ex vivo flow-loop system. MNP/LV complexes allowed for eGFP expression in the endothelium of the vessel after 4–6 days of culture while perfusion with LVs alone did not result in transduction and protein expression.

Conclusion: 

This approach in combination with the application of therapeutic genes could restore the physiological vascular endothelial function ex vivo and in vivo. Moreover, this technique could be adapted to allow for EC replacement in injured vessels by magnetic targeting of cells loaded with MNPs.