title: 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.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Adamo
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Ilia
authors.initials: I
authors.lastname: Fishbein
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Kehan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Levy
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Alferiev
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: chorny@email.chop.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Chorny
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry; D020212:Carotid Artery Injuries / Q000628:therapy*; D015925:Cryopreservation; D042783:Endothelial Cells / Q000637:transplantation*; D005456:Fluorescent Dyes / Q000737:chemistry; D060328:Magnetic Phenomena; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D015607:Stents
chemical_list: C530973:4,4-difluoro-5-(2-thienyl)-4-bora-3a,4a-diaza-s-indacene-3-dodecanoic acid; D001896:Boron Compounds; D005456:Fluorescent Dyes; D011091:Polyesters; C033616:poly(lactide)
keywords: Accelerated reendothelialization; Arterial injury; Endothelium regrowth; Magnetic guidance; Nanoparticle degradation; Stent angioplasty