Magnetically enhanced cell delivery for accelerating recovery of the endothelium in injured arteries

Abstract

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.

Effect of working environment and procedural strategies on mechanical performance of bioresorbable vascular scaffolds

“…These permanent foreign objects residing inside living arteries may interfere with vascular repair and lead to various long-term complications [1–7]. Although various approaches have been investigated to improve the performance of these devices [8,9], fundamental limitations associated with metal stents drove the community toward bioresorbable scaffolds (BRS). The emergence of BRS allows implants to be inserted and then degrade over time, leaving an intact vessel.…”

Magnetizable stent-grafts enable endothelial cell capture

“…The ferromagnetic stent-graft studied in this report is the first of its kind and enables a variety of magnetic targeting applications including cell, drug, and gene delivery. Our group and others have previously demonstrated the benefits of delivering cells [9, 10, 16, 17], drugs [18–21], and genes [22] to magnetized stents as well as cells to injured vessels [23, 24]. Stent-grafts have distinct indications from those of stents, such as repair of weakened or damaged vessels, and a magnetic stent-graft allows additional patient populations to benefit from the magnetic targeting approach.…”

The Multifaceted Uses and Therapeutic Advantages of Nanoparticles for Atherosclerosis Research

“…Alternatively, Adamo et al investigated the delivery of cells as therapeutics. By introducing biodegradable PLA-based magnetic nanoparticles in vitro into rat aortic endothelial cells, the authors were able to load ECs with nanomagnets [ 75 ]. The treatment was intended for mechanical injury following stent implantation that can often leave the endothelium damaged but this work could be applicable for atherosclerosis.…”