Arterial injury and disruption of the endothelial layer are an inevitable
consequence of interventional procedures used for treating obstructive vascular
disease. The slow and often incomplete endothelium regrowth after injury is the
primary cause of serious short- and long-term complications, including
thrombosis, restenosis and neoatherosclerosis. Rapid endothelium restoration has
the potential to prevent these sequelae, providing a rationale for developing
strategies aimed at accelerating the reendothelialization process. The present
studies focused on magnetically guided delivery of endothelial cells (EC)
functionalized with biodegradable magnetic nanoparticles (MNP) as an
experimental approach for achieving rapid and stable cell homing and expansion
in stented arteries. EC laden with polylactide-based MNP exhibited strong
magnetic responsiveness, capacity for cryopreservation and rapid expansion, and
the ability to disintegrate internalized MNP in both proliferating and
contact-inhibited states. Intracellular decomposition of
BODIPY558/568-labeled MNP monitored non-invasively based on
assembly state-dependent changes in the emission spectrum demonstrated cell
proliferation rate-dependent kinetics (average disassembly rates: 6.6 ±
0.8% and 3.6 ± 0.4% per day in dividing and
contact-inhibited EC, respectively). With magnetic guidance using a transient
exposure to a uniform 1-kOe field, stable localization and subsequent
propagation of MNP-functionalized EC, markedly enhanced in comparison to
non-magnetic delivery conditions, were observed in stented rat carotid arteries.
In conclusion, magnetically guided delivery is a promising experimental strategy
for accelerating endothelial cell repopulation of stented blood vessels after
angioplasty.