title: Determining the fate of seeded cells in venous tissue-engineered vascular grafts using serial MRI.
abstract: A major limitation of tissue engineering research is the lack of noninvasive monitoring techniques for observations of dynamic changes in single tissue-engineered constructs. We use cellular magnetic resonance imaging (MRI) to track the fate of cells seeded onto functional tissue-engineered vascular grafts (TEVGs) through serial imaging. After in vitro optimization, murine macrophages were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and seeded onto scaffolds that were surgically implanted as inferior vena cava interposition grafts in SCID/bg mice. Serial MRI showed the transverse relaxation times (T(2)) were significantly lower immediately following implantation of USPIO-labeled scaffolds (T(2) = 44 ± 6.8 vs. 71 ± 10.2 ms) but increased rapidly at 2 h to values identical to control implants seeded with unlabeled macrophages (T(2) = 63 ± 12 vs. 63 ± 14 ms). This strongly indicates the rapid loss of seeded cells from the scaffolds, a finding verified using Prussian blue staining for iron containing macrophages on explanted TEVGs. Our results support a novel paradigm where seeded cells are rapidly lost from implanted scaffolds instead of developing into cells of the neovessel, as traditionally thought. Our findings confirm and validate this paradigm shift while demonstrating the first successful application of noninvasive MRI for serial study of cellular-level processes in tissue engineering.
authors.affiliation: Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Harrington
authors.forename: Halima
authors.initials: H
authors.lastname: Chahboune
authors.forename: Jason M
authors.initials: JM
authors.lastname: Criscione
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Li
authors.forename: Narutoshi
authors.initials: N
authors.lastname: Hibino
authors.forename: Tai
authors.initials: T
authors.lastname: Yi
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Villalona
authors.forename: Serge
authors.initials: S
authors.lastname: Kobsa
authors.forename: Dane
authors.initials: D
authors.lastname: Meijas
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Duncan
authors.forename: Lesley
authors.initials: L
authors.lastname: Devine
authors.forename: Xenophon
authors.initials: X
authors.lastname: Papademetri
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shin'oka
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Fahmy
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D002460:Cell Line; D002470:Cell Survival; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D016513:Mice, SCID; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014682:Vena Cava, Inferior / Q000166:cytology / Q000601:surgery
chemical_list: D058185:Magnetite Nanoparticles